Respiratory Distress Syndrome (RDS)
Conditions
Keywords
Less Invasive Surfactant administration, LISPAP, Neonates, Newborns, Respiratory Distress Syndrome (RDS), CUROSURF®
Brief summary
This study compared the administration of porcine surfactant (poractant alfa, Curosurf®) through a less invasive method (LISA), using a thin catheter, CHF 6440 (LISACATH®), during non-invasive ventilation (CPAP, NIPPV, BiPAP) with an approved conventional surfactant administration during invasive ventilation followed by rapid extubation in terms of short term and mid-term safety and efficacy in spontaneously breathing preterm neonates who have clinical signs of respiratory distress syndrome (RDS).
Detailed description
This study was an open-label, multicentre, randomized, controlled study of spontaneously breathing neonates with RDS. Neonates were evaluated according to the selection criteria and then randomized to surfactant treatment via LISA or standard administration procedure. The enrolment was staggered: the gestational age was restricted to 27+0 weeks up to 28+6 weeks for the first 15 neonates. Provided no safety concerns were raised, the enrolment was planned to be extended to the whole population (i.e. 25+0 weeks up to 28+6 weeks). Enrolled neonates were evaluated in a main phase of the trial until discharge or 40 weeks post-menstrual age (PMA), whichever came first. Their clinical status and neurodevelopment was to be assessed at 24-month corrected age as a separate stand-alone visit. The Sponsor decided to terminate the study early, due to uncertain sufficient availability of the CHF 6440 catheter.
Interventions
COMBINATION_PRODUCTLISA combination product (Curosurf+catheter CHF6440)
Curosurf administration through brief insertion of a thin catheter into the trachea
DRUGCurosurf through conventional administration (endotracheal tube)
Curosurf through conventional administration (endotracheal tube), followed by rapid extubation
Sponsors
Chiesi Farmaceutici S.p.A.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
30 Minutes to 24 Hours
Healthy volunteers
No
Inclusion criteria
1. Written informed consent obtained by parents/legal representative (according to local regulation) prior to or after birth 2. Preterm neonates of either sex aged ≥30 minutes and \<24 hours, spontaneously breathing and stabilized on non-invasive ventilation (NIV). 3. Gestational age of 25+0 weeks up to 28+6 completed weeks, except for the first 15 enrolled neonates in which the gestational age will be restricted to 27+0 weeks up to 28+6 weeks. 4. Clinical course consistent with RDS. 5. Fraction of inspired oxygen (FiO2) ≥0.30 to maintain preductal oxygen saturation (SpO2) between 88-95%.
Exclusion criteria
1. Need for immediate endotracheal intubation for cardiopulmonary resuscitation or insufficient respiratory drive 2. Use of nasal high frequency oscillatory ventilation (nHFOV) prior to study entry 3. Use of surfactant prior to study entry and need for intratracheal administration of any other treatment (e.g. nitric oxide) 4. Known genetic or chromosomal disorders, major congenital anomalies (congenital heart diseases, myelomeningocele etc) 5. Mothers with prolonged rupture of the membranes (\> 21 days duration) 6. Presence of air leaks if identified and known prior to study entry 7. Evidence of severe birth asphyxia (e.g. continued need for resuscitation at 10 minutes after birth, altered neurological state, or neonatal encephalopathy) 8. Neonatal seizures prior to study entry 9. Any condition that, in the opinion of the Investigator, would place the neonate at undue risk 10. Participation in another clinical trial of any medicinal product, placebo, experimental medical device, or biological substance conducted under the provisions of a protocol on the same therapeutic target.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety: Study Treatment Administration: Number of Participants Who Received 1, 2, or 3 Doses of Treatment | First 72 hours of life. | Extent of exposure to study treatment is summarized by treatment group. Number of participants who received 1, 2, or 3 doses of treatment. All neonates received the first administration of Curosurf® 200 mg/kg. In case of lack of efficacy or clinical deterioration, a second dose of Curosurf® 100 mg/kg was administered using the same technique as the first dose. Neonates could receive a third Curosurf® 100 mg/kg dose if needed, administered using a standard technique. Results are presented as the number of neonates who received 1, 2, or 3 doses of Curosurf®, administered. |
| Safety: Study Treatment Administration: Number of Participants for Whom the First Attempt Failed to Insert the Catheter/Endotracheal Tube | At first surfactant administration, up to Day 1. | Number of participants for whom the first attempt failed to insert the catheter/endotracheal tube and the percentage of neonates with first failed attempt, is presented by treatment group. |
| Safety: Study Treatment Administration: Number of Maneuvers Discontinued Due to Neonate's Severe Destabilization | At first surfactant administration, up to Day 1 or at second administration, up to 2 days. | Number of manoeuvres (attempts) discontinued, due to neonate's severe destabilization is presented by treatment group. |
| Safety: Study Treatment Administration: Number of Attempts to First Successful Insertion | At first surfactant administration, up to Day 1 or at second administration, up to 2 days. | Number of attempts required to achieve first successful insertion is presented by treatment group. |
| Safety: Study Treatment Administration: Number of Device Misallocation for LISA Administration Group (Esophageal Insertion) | At first surfactant administration, up to Day 1 or at second administration, up to 2 days. | Number of device misallocation for LISA administration group (esophageal insertion). Data was not collected from participants in the Curosurf Endotracheal Tube -- the control arm of the study, because it is not applicable. |
| Safety: Study Treatment Administration: Duration of Surfactant Administration | At first surfactant administration, up to Day 1 or at second administration, up to 2 days. | Duration of surfactant administration is presented by treatment group. |
| Safety: Study Treatment Administration: Duration of the Whole Procedure | At first surfactant administration, up to Day 1 or at second administration, up to 2 days. | Duration of the whole procedure (starting from the insertion of laryngoscope up to the removal of the catheter/ETT), is presented by treatment group. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy: Median Duration of Invasive Mechanical Ventilation During the Study | Up to 28 days PNA, Up to 36 weeks PMA | The duration of invasive ventilation (MV) in the first 28 days PNA, and within 36 weeks PMA, are presented by treatment group. Participants who actually received invasive ventilation are reported in the table below. |
| Efficacy: Duration of Invasive Mechanical Ventilation During the Study | First 72 hours of life | The duration of invasive ventilation (MV) in the first 72 hours of life and respective statistical analyses, are presented by treatment group. |
| Efficacy: Percentage of Neonates Needing Invasive Mechanical Ventilation (MV) During the Study | First 72 hours of life, Up to 28 days Post-Natal Age (PNA), Up to 36 weeks PMA | The percentage of neonates needing invasive mechanical ventilation (MV) in the first 72 hours of life, in the first 28 days post-natal age (PNA), and within 36 weeks Post-Menstrual Age (PMA), and respective statistical analyses, are presented by treatment group. |
| Efficacy: Blood Gas Analysis Parameters -- pH | First 72 hours of life (1h, 6h, 24h, 48h, 72h) | The blood gas analysis for blood pH at all timepoints and the changes from pre-procedure to each timepoint are presented. Results for pH values are based on a scale of 0 to 14. A pH value of 7 is neutral, pH less than 7 is acidic, and pH greater than 7 is basic. |
| Efficacy: Duration of Oxygen Alone Supplementation and Any Non-Invasive Ventilation (NIV) | First 72 hours of life, Up to 28 days Post-Natal Age (PNA), Up to 36 weeks Post-Menstrual Age (PMA). | The duration of oxygen alone supplementation and any non-invasive ventilation (NIV) during the study are presented by treatment group. PMA=Post-Menstrual Age PNA=Post-Natal Age |
| Efficacy: Blood Gas Analysis Parameters -- Partial Pressure of Oxygen (pO2) | First 72 hours of life (1h, 6h, 24h, 48h, 72h) | The blood gas analysis partial pressure of oxygen (pO2) at all timepoints and the changes from pre-procedure to each timepoint are presented. |
| Efficacy: Blood Analysis Parameter -- Bicarbonate (HCO3^-) | First 72 hours of life (1h, 6h, 24h, 48h, 72h) | The blood concentration of bicarbonate (HCO3\^-) at all timepoints and the changes from pre-procedure to each timepoint are presented. |
| Efficacy: Blood Analysis Parameter -- Base Excess | First 72 hours of life (1h, 6h, 24h, 48h, 72h) | The blood base excess at all timepoints and the changes from pre-procedure to each timepoint are presented. Base excess is defined as the amount of acid that must be added to each litre of fully oxygenated blood to return the pH to 7.40 at a temperature of 37°C and a pCO2 of 40 mmHg (5.3 kPa). The value is reported as a concentration in units of milliequivalent per liter (mEq/L), with positive numbers indicating an excess of base and negative a deficit. |
| Efficacy: Blood Analysis Parameter -- Lactate | First 72 hours of life (1h, 6h, 24h, 48h, 72h) | The blood concentration of lactate at all timepoints and the changes from pre-procedure to each timepoint are presented. |
| Efficacy: Blood Gas Analysis Parameters -- Partial Pressure of Carbon Dioxide (pCO2) | First 72 hours of life (1h, 6h, 24h, 48h, 72h) | The blood gas analysis partial pressure of carbon dioxide (pCO2) at all timepoints and the changes from pre-procedure to each timepoint are presented. |
| Efficacy: Neonates Needing Additional 2 or 3 Doses of Surfactant | First 72 hours of life. | A summary of the percentage of neonates requiring at least one additional dose of surfactant, and respective statistical analysis, is presented by treatment group i.e. 2 or 3 doses of surfactant . |
| Efficacy: Neonates Needing Additional Surfactant Doses | First 72 hours of life. | A summary of the percentage of neonates requiring at least one additional dose of surfactant, and respective statistical analysis, is presented by treatment group. |
| Efficacy: Preductal Oxygen Saturation/Fraction of Inspired Oxygen (SpO2/FiO2) Ratio | Pre-procedure, at time 0 (T0, end of surfactant instillation) and post treatment after T0 at 5, 15, 30 minutes, at 1, 6, 12, 24, 48, 72, and 120 hours, on Day 28 PNA, 36 weeks PMA. | The mean SpO2/FiO2 ratio values at timepoints up to and including 120 hours post-treatment, and respective statistical analyses, are summarized by treatment group. |
| Efficacy: Fraction of Inspired Oxygen (FiO2) | Pre-procedure, at time 0 (T0, end of surfactant instillation) and post treatment after T0 at 5, 15, 30 minutes, at 1, 6, 12, 24, 48, 72, and 120 hours, on Day 28 PNA, 36 weeks PMA. | The FiO2 values at timepoints up to and including 120 hours post-treatment and the changes from pre-procedure to each of those timepoints are presented by treatment group. The fraction of inspired oxygen (FiO2) is the concentration of oxygen in the gas mixture. |
| Efficacy: Preductal Oxygen Saturation (SpO2) | Pre-procedure, at time 0 (T0, end of surfactant instillation) and post treatment after T0 at 5, 15, 30 minutes, at 1, 6, 12, 24, 48, 72, and 120 hours, on Day 28 PNA, 36 weeks PMA. | The mean SpO2 values at timepoints up to and including 120 hours post-treatment are summarized by treatment group. Oxygen saturation (SpO2) is a measurement of how much oxygen the blood is carrying as a percentage of the maximum it could carry. |
| Efficacy: Percentage of Neonates Needing Any Intubation Procedure, Outside the Initial Surfactant Administration Period | First 72 hours of life, up to 28 days post-natal age (PNA), Up to 36 weeks Post-menstrual age (PMA) | The percentage of neonates needing any intubation procedure, outside the initial surfactant administration period (i.e., excluding endotracheal intubation\[s\] that were required for surfactant administration in the Conventional administration arm), in the first 72 hours of life, in the first 28 days post-natal age (PNA), and within 36 weeks Post-menstrual age (PMA), and respective statistical analyses, are presented. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Curosurf LISA Single dose of poractant alfa 200 mg/kg via brief insertion of a thin catheter (CHF 6440) into the trachea in neonates with RDS.
A second surfactant dose at 100 mg/kg will be administered with the same technique as the first dosage administration if needed.
After the first and second surfactant administration, neonates could receive a third surfactant dose at 100 mg/kg through a standard technique if needed.
LISA combination product (Curosurf+catheter CHF6440): Curosurf administration through brief insertion of a thin catheter into the trachea | 19 |
| Curosurf Endotracheal Tube Single dose of poractant alfa 200 mg/kg via the conventional intubation with endotracheal tube in neonates with RDS.
A second surfactant dose at 100 mg/kg will be administered with the same technique as the first dosage administration if needed.
After the first and second surfactant administration, neonates could receive a third surfactant dose at 100 mg/kg through a standard technique if needed.
Curosurf through conventional administration (endotracheal tube): Curosurf through conventional administration (endotracheal tube), followed by rapid extubation | 12 |
| Total | 31 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 1 | 1 |
| Overall Study | Physician Decision | 1 | 1 |
Baseline characteristics
| Characteristic | Curosurf LISA | Curosurf Endotracheal Tube | Total |
|---|---|---|---|
| Age, Continuous | 27.65 weeks | 27.92 weeks | 27.76 weeks |
| Antibiotics taken - YES | 9 Participants | 8 Participants | 17 Participants |
| APGAR score at 1 minute post-birth | 5.6 scores on a scale | 4.8 scores on a scale | 5.3 scores on a scale |
| APGAR score at 5 minutes post-birth | 7.5 APGAR score | 7.7 APGAR score | 7.6 APGAR score |
| Birth weight | 1.009 kg | 0.973 kg | 0.995 kg |
| Corticosteroids taken -- YES | 14 Participants | 11 Participants | 25 Participants |
| Mother's age | 30.0 years | 25.8 years | 28.4 years |
| Mother's ethnicity Data missing | 1 Participants | 1 Participants | 2 Participants |
| Mother's ethnicity Hispanic or Latino | 5 Participants | 6 Participants | 11 Participants |
| Mother's ethnicity Not Hispanic or Latino | 13 Participants | 5 Participants | 18 Participants |
| Mother's race American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Mother's race Asian | 1 Participants | 0 Participants | 1 Participants |
| Mother's race Black or African American | 4 Participants | 3 Participants | 7 Participants |
| Mother's race Unknown or Not Reported | 2 Participants | 1 Participants | 3 Participants |
| Mother's race White | 11 Participants | 8 Participants | 19 Participants |
| Number of days from last corticosteroid dose up to birth, 0-1 days | 8 days | 5 days | 13 days |
| Number of days from last corticosteroid dose up to birth, 2-7 days | 3 days | 6 days | 9 days |
| Number of days from last corticosteroid dose up to birth, >7 days | 3 days | 0 days | 3 days |
| Race/Ethnicity, Customized Hispanic or Latino | 5 participants | 6 participants | 11 participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 14 participants | 6 participants | 20 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 3 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 2 Participants | 5 Participants |
| Race (NIH/OMB) White | 11 Participants | 7 Participants | 18 Participants |
| Region of Enrollment United States | 19 participants | 12 participants | 31 participants |
| Sex: Female, Male Female | 8 Participants | 5 Participants | 13 Participants |
| Sex: Female, Male Male | 11 Participants | 7 Participants | 18 Participants |
| Type of delivery C-section with labor | 2 Participants | 3 Participants | 5 Participants |
| Type of delivery C-section without labor | 10 Participants | 4 Participants | 14 Participants |
| Type of delivery Emergency C-section | 5 Participants | 3 Participants | 8 Participants |
| Type of delivery Spontaneous | 2 Participants | 2 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 19 | 1 / 12 |
| other Total, other adverse events | 19 / 19 | 12 / 12 |
| serious Total, serious adverse events | 1 / 19 | 2 / 12 |
Outcome results
Primary
Safety: Study Treatment Administration: Duration of Surfactant Administration
Duration of surfactant administration is presented by treatment group.
Time frame: At first surfactant administration, up to Day 1 or at second administration, up to 2 days.
Population: Safety population (SAF): All randomized neonates who received at least one dose of study treatment.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Curosurf LISA | Safety: Study Treatment Administration: Duration of Surfactant Administration | First administration | 1.8 minutes |
| Curosurf LISA | Safety: Study Treatment Administration: Duration of Surfactant Administration | Second administration | 2.3 minutes |
| Curosurf Endotracheal Tube | Safety: Study Treatment Administration: Duration of Surfactant Administration | First administration | 2.3 minutes |
| Curosurf Endotracheal Tube | Safety: Study Treatment Administration: Duration of Surfactant Administration | Second administration | 1.7 minutes |
Primary
Safety: Study Treatment Administration: Duration of the Whole Procedure
Duration of the whole procedure (starting from the insertion of laryngoscope up to the removal of the catheter/ETT), is presented by treatment group.
Time frame: At first surfactant administration, up to Day 1 or at second administration, up to 2 days.
Population: Safety population (SAF): All randomized neonates who received at least one dose of study treatment.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Curosurf LISA | Safety: Study Treatment Administration: Duration of the Whole Procedure | First administration | 3.9 minutes |
| Curosurf LISA | Safety: Study Treatment Administration: Duration of the Whole Procedure | Second administration | 5.8 minutes |
| Curosurf Endotracheal Tube | Safety: Study Treatment Administration: Duration of the Whole Procedure | First administration | 7.8 minutes |
| Curosurf Endotracheal Tube | Safety: Study Treatment Administration: Duration of the Whole Procedure | Second administration | 3.0 minutes |
Primary
Safety: Study Treatment Administration: Number of Attempts to First Successful Insertion
Number of attempts required to achieve first successful insertion is presented by treatment group.
Time frame: At first surfactant administration, up to Day 1 or at second administration, up to 2 days.
Population: Safety population (SAF): All randomized neonates who received at least one dose of study treatment.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Curosurf LISA | Safety: Study Treatment Administration: Number of Attempts to First Successful Insertion | First administration | 1.3 Number of maneuvers (attempts) |
| Curosurf LISA | Safety: Study Treatment Administration: Number of Attempts to First Successful Insertion | Second administration | 2.0 Number of maneuvers (attempts) |
| Curosurf Endotracheal Tube | Safety: Study Treatment Administration: Number of Attempts to First Successful Insertion | First administration | 1.8 Number of maneuvers (attempts) |
| Curosurf Endotracheal Tube | Safety: Study Treatment Administration: Number of Attempts to First Successful Insertion | Second administration | 1.0 Number of maneuvers (attempts) |
Primary
Safety: Study Treatment Administration: Number of Device Misallocation for LISA Administration Group (Esophageal Insertion)
Number of device misallocation for LISA administration group (esophageal insertion). Data was not collected from participants in the Curosurf Endotracheal Tube -- the control arm of the study, because it is not applicable.
Time frame: At first surfactant administration, up to Day 1 or at second administration, up to 2 days.
Population: Safety population (SAF): All randomized neonates who received at least one dose of study treatment.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Curosurf LISA | Safety: Study Treatment Administration: Number of Device Misallocation for LISA Administration Group (Esophageal Insertion) | First administration | 0.2 Number of maneuvers (attempts) |
| Curosurf LISA | Safety: Study Treatment Administration: Number of Device Misallocation for LISA Administration Group (Esophageal Insertion) | Second administration | 0.0 Number of maneuvers (attempts) |
Primary
Safety: Study Treatment Administration: Number of Maneuvers Discontinued Due to Neonate's Severe Destabilization
Number of manoeuvres (attempts) discontinued, due to neonate's severe destabilization is presented by treatment group.
Time frame: At first surfactant administration, up to Day 1 or at second administration, up to 2 days.
Population: Safety population (SAF): All randomized neonates who received at least one dose of study treatment.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Curosurf LISA | Safety: Study Treatment Administration: Number of Maneuvers Discontinued Due to Neonate's Severe Destabilization | First administration | 0.1 Number of maneuvers (attempts) |
| Curosurf LISA | Safety: Study Treatment Administration: Number of Maneuvers Discontinued Due to Neonate's Severe Destabilization | Second administration | 0.3 Number of maneuvers (attempts) |
| Curosurf Endotracheal Tube | Safety: Study Treatment Administration: Number of Maneuvers Discontinued Due to Neonate's Severe Destabilization | First administration | 0.0 Number of maneuvers (attempts) |
| Curosurf Endotracheal Tube | Safety: Study Treatment Administration: Number of Maneuvers Discontinued Due to Neonate's Severe Destabilization | Second administration | 0.0 Number of maneuvers (attempts) |
Primary
Safety: Study Treatment Administration: Number of Participants for Whom the First Attempt Failed to Insert the Catheter/Endotracheal Tube
Number of participants for whom the first attempt failed to insert the catheter/endotracheal tube and the percentage of neonates with first failed attempt, is presented by treatment group.
Time frame: At first surfactant administration, up to Day 1.
Population: Safety population (SAF): All randomized neonates who received at least one dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Curosurf LISA | Safety: Study Treatment Administration: Number of Participants for Whom the First Attempt Failed to Insert the Catheter/Endotracheal Tube | 5 Participants |
| Curosurf Endotracheal Tube | Safety: Study Treatment Administration: Number of Participants for Whom the First Attempt Failed to Insert the Catheter/Endotracheal Tube | 5 Participants |
Comparison: First Administration; Treatment comparison. Adjusted difference, its 95% confidence interval (CI) and p-value are estimated using Cochran-Mantel-Haenszel testp-value: 0.3995% CI: [-47.9, 17.1]Cochran-Mantel-Haenszel
Primary
Safety: Study Treatment Administration: Number of Participants Who Received 1, 2, or 3 Doses of Treatment
Extent of exposure to study treatment is summarized by treatment group. Number of participants who received 1, 2, or 3 doses of treatment. All neonates received the first administration of Curosurf® 200 mg/kg. In case of lack of efficacy or clinical deterioration, a second dose of Curosurf® 100 mg/kg was administered using the same technique as the first dose. Neonates could receive a third Curosurf® 100 mg/kg dose if needed, administered using a standard technique. Results are presented as the number of neonates who received 1, 2, or 3 doses of Curosurf®, administered.
Time frame: First 72 hours of life.
Population: Safety population (SAF): All randomized neonates who received at least one dose of study treatment.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Curosurf LISA | Safety: Study Treatment Administration: Number of Participants Who Received 1, 2, or 3 Doses of Treatment | Number of Curosurf® dose, n=1 dose | 13 Participants |
| Curosurf LISA | Safety: Study Treatment Administration: Number of Participants Who Received 1, 2, or 3 Doses of Treatment | Number of Curosurf® doses, n=2 doses | 4 Participants |
| Curosurf LISA | Safety: Study Treatment Administration: Number of Participants Who Received 1, 2, or 3 Doses of Treatment | Number of Curosurf® doses, n=3 doses | 2 Participants |
| Curosurf Endotracheal Tube | Safety: Study Treatment Administration: Number of Participants Who Received 1, 2, or 3 Doses of Treatment | Number of Curosurf® dose, n=1 dose | 9 Participants |
| Curosurf Endotracheal Tube | Safety: Study Treatment Administration: Number of Participants Who Received 1, 2, or 3 Doses of Treatment | Number of Curosurf® doses, n=2 doses | 2 Participants |
| Curosurf Endotracheal Tube | Safety: Study Treatment Administration: Number of Participants Who Received 1, 2, or 3 Doses of Treatment | Number of Curosurf® doses, n=3 doses | 1 Participants |
Secondary
Efficacy: Blood Analysis Parameter -- Base Excess
The blood base excess at all timepoints and the changes from pre-procedure to each timepoint are presented. Base excess is defined as the amount of acid that must be added to each litre of fully oxygenated blood to return the pH to 7.40 at a temperature of 37°C and a pCO2 of 40 mmHg (5.3 kPa). The value is reported as a concentration in units of milliequivalent per liter (mEq/L), with positive numbers indicating an excess of base and negative a deficit.
Time frame: First 72 hours of life (1h, 6h, 24h, 48h, 72h)
Population: Intention-to-treat population (ITT): All randomized neonates who received at least one dose of study treatment.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Curosurf LISA | Efficacy: Blood Analysis Parameter -- Base Excess | Pre-procedure (actual value) | -3.20 mEq/L |
| Curosurf LISA | Efficacy: Blood Analysis Parameter -- Base Excess | 1 h - post procedure (Change from pre-procedure to 1 hour post-procedure) | -0.49 mEq/L |
| Curosurf LISA | Efficacy: Blood Analysis Parameter -- Base Excess | 6 h - post procedure (Change from pre-procedure to 6 hour post-procedure) | -0.10 mEq/L |
| Curosurf LISA | Efficacy: Blood Analysis Parameter -- Base Excess | 24 h - post procedure (Change from pre-procedure to 24 hour post-procedure) | 0.16 mEq/L |
| Curosurf LISA | Efficacy: Blood Analysis Parameter -- Base Excess | 48 h - post procedure (Change from pre-procedure to 48 hour post-procedure) | -0.29 mEq/L |
| Curosurf LISA | Efficacy: Blood Analysis Parameter -- Base Excess | 72 h - post procedure (Change from pre-procedure to 72 hour post-procedure) | -0.97 mEq/L |
| Curosurf Endotracheal Tube | Efficacy: Blood Analysis Parameter -- Base Excess | 48 h - post procedure (Change from pre-procedure to 48 hour post-procedure) | 3.21 mEq/L |
| Curosurf Endotracheal Tube | Efficacy: Blood Analysis Parameter -- Base Excess | Pre-procedure (actual value) | -5.22 mEq/L |
| Curosurf Endotracheal Tube | Efficacy: Blood Analysis Parameter -- Base Excess | 24 h - post procedure (Change from pre-procedure to 24 hour post-procedure) | 2.17 mEq/L |
| Curosurf Endotracheal Tube | Efficacy: Blood Analysis Parameter -- Base Excess | 1 h - post procedure (Change from pre-procedure to 1 hour post-procedure) | 1.07 mEq/L |
| Curosurf Endotracheal Tube | Efficacy: Blood Analysis Parameter -- Base Excess | 72 h - post procedure (Change from pre-procedure to 72 hour post-procedure) | 2.37 mEq/L |
| Curosurf Endotracheal Tube | Efficacy: Blood Analysis Parameter -- Base Excess | 6 h - post procedure (Change from pre-procedure to 6 hour post-procedure) | 1.61 mEq/L |
Secondary
Efficacy: Blood Analysis Parameter -- Bicarbonate (HCO3^-)
The blood concentration of bicarbonate (HCO3\^-) at all timepoints and the changes from pre-procedure to each timepoint are presented.
Time frame: First 72 hours of life (1h, 6h, 24h, 48h, 72h)
Population: Intention-to-treat population (ITT): All randomized neonates who received at least one dose of study treatment.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Curosurf LISA | Efficacy: Blood Analysis Parameter -- Bicarbonate (HCO3^-) | Pre-procedure (actual value) | 23.4 mmol/L |
| Curosurf LISA | Efficacy: Blood Analysis Parameter -- Bicarbonate (HCO3^-) | 1 h - post procedure (Change from pre-procedure to 1 hour post-procedure) | -0.7 mmol/L |
| Curosurf LISA | Efficacy: Blood Analysis Parameter -- Bicarbonate (HCO3^-) | 6 h - post procedure (Change from pre-procedure to 6 hour post-procedure) | -1.1 mmol/L |
| Curosurf LISA | Efficacy: Blood Analysis Parameter -- Bicarbonate (HCO3^-) | 24 h - post procedure (Change from pre-procedure to 24 hour post-procedure) | -0.5 mmol/L |
| Curosurf LISA | Efficacy: Blood Analysis Parameter -- Bicarbonate (HCO3^-) | 48 h - post procedure (Change from pre-procedure to 48 hour post-procedure) | -0.9 mmol/L |
| Curosurf LISA | Efficacy: Blood Analysis Parameter -- Bicarbonate (HCO3^-) | 72 h - post procedure (Change from pre-procedure to 72 hour post-procedure) | -1.1 mmol/L |
| Curosurf Endotracheal Tube | Efficacy: Blood Analysis Parameter -- Bicarbonate (HCO3^-) | 48 h - post procedure (Change from pre-procedure to 48 hour post-procedure) | 1.2 mmol/L |
| Curosurf Endotracheal Tube | Efficacy: Blood Analysis Parameter -- Bicarbonate (HCO3^-) | Pre-procedure (actual value) | 22.1 mmol/L |
| Curosurf Endotracheal Tube | Efficacy: Blood Analysis Parameter -- Bicarbonate (HCO3^-) | 24 h - post procedure (Change from pre-procedure to 24 hour post-procedure) | 0.6 mmol/L |
| Curosurf Endotracheal Tube | Efficacy: Blood Analysis Parameter -- Bicarbonate (HCO3^-) | 1 h - post procedure (Change from pre-procedure to 1 hour post-procedure) | 1.1 mmol/L |
| Curosurf Endotracheal Tube | Efficacy: Blood Analysis Parameter -- Bicarbonate (HCO3^-) | 72 h - post procedure (Change from pre-procedure to 72 hour post-procedure) | 0.8 mmol/L |
| Curosurf Endotracheal Tube | Efficacy: Blood Analysis Parameter -- Bicarbonate (HCO3^-) | 6 h - post procedure (Change from pre-procedure to 6 hour post-procedure) | 1.5 mmol/L |
Secondary
Efficacy: Blood Analysis Parameter -- Lactate
The blood concentration of lactate at all timepoints and the changes from pre-procedure to each timepoint are presented.
Time frame: First 72 hours of life (1h, 6h, 24h, 48h, 72h)
Population: Intention-to-treat population (ITT): All randomized neonates who received at least one dose of study treatment.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Curosurf LISA | Efficacy: Blood Analysis Parameter -- Lactate | Pre-procedure (actual value) | 2.047 mmol/L |
| Curosurf LISA | Efficacy: Blood Analysis Parameter -- Lactate | 1 h - post procedure (Change from pre-procedure to 1 hour post-procedure) | 0.311 mmol/L |
| Curosurf LISA | Efficacy: Blood Analysis Parameter -- Lactate | 6 h - post procedure (Change from pre-procedure to 6 hour post-procedure) | 0.425 mmol/L |
| Curosurf LISA | Efficacy: Blood Analysis Parameter -- Lactate | 24 h - post procedure (Change from pre-procedure to 24 hour post-procedure) | 0.009 mmol/L |
| Curosurf LISA | Efficacy: Blood Analysis Parameter -- Lactate | 48 h - post procedure (Change from pre-procedure to 48 hour post-procedure) | -0.284 mmol/L |
| Curosurf LISA | Efficacy: Blood Analysis Parameter -- Lactate | 72 h - post procedure (Change from pre-procedure to 72 hour post-procedure) | -0.418 mmol/L |
| Curosurf Endotracheal Tube | Efficacy: Blood Analysis Parameter -- Lactate | 48 h - post procedure (Change from pre-procedure to 48 hour post-procedure) | -2.168 mmol/L |
| Curosurf Endotracheal Tube | Efficacy: Blood Analysis Parameter -- Lactate | Pre-procedure (actual value) | 2.825 mmol/L |
| Curosurf Endotracheal Tube | Efficacy: Blood Analysis Parameter -- Lactate | 24 h - post procedure (Change from pre-procedure to 24 hour post-procedure) | -1.100 mmol/L |
| Curosurf Endotracheal Tube | Efficacy: Blood Analysis Parameter -- Lactate | 1 h - post procedure (Change from pre-procedure to 1 hour post-procedure) | -0.188 mmol/L |
| Curosurf Endotracheal Tube | Efficacy: Blood Analysis Parameter -- Lactate | 72 h - post procedure (Change from pre-procedure to 72 hour post-procedure) | -1.656 mmol/L |
| Curosurf Endotracheal Tube | Efficacy: Blood Analysis Parameter -- Lactate | 6 h - post procedure (Change from pre-procedure to 6 hour post-procedure) | -0.802 mmol/L |
Secondary
Efficacy: Blood Gas Analysis Parameters -- Partial Pressure of Carbon Dioxide (pCO2)
The blood gas analysis partial pressure of carbon dioxide (pCO2) at all timepoints and the changes from pre-procedure to each timepoint are presented.
Time frame: First 72 hours of life (1h, 6h, 24h, 48h, 72h)
Population: Intention-to-treat population (ITT): All randomized neonates who received at least one dose of study treatment.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Curosurf LISA | Efficacy: Blood Gas Analysis Parameters -- Partial Pressure of Carbon Dioxide (pCO2) | Pre-procedure (actual value) | 50.30 mmHg |
| Curosurf LISA | Efficacy: Blood Gas Analysis Parameters -- Partial Pressure of Carbon Dioxide (pCO2) | 1 h - post procedure (Change from pre-procedure to 1 hour post-procedure) | -4.00 mmHg |
| Curosurf LISA | Efficacy: Blood Gas Analysis Parameters -- Partial Pressure of Carbon Dioxide (pCO2) | 6 h - post procedure (Change from pre-procedure to 6 hour post-procedure) | -7.55 mmHg |
| Curosurf LISA | Efficacy: Blood Gas Analysis Parameters -- Partial Pressure of Carbon Dioxide (pCO2) | 24 h - post procedure (Change from pre-procedure to 24 hour post-procedure) | -6.12 mmHg |
| Curosurf LISA | Efficacy: Blood Gas Analysis Parameters -- Partial Pressure of Carbon Dioxide (pCO2) | 48 h - post procedure (Change from pre-procedure to 48 hour post-procedure) | -2.70 mmHg |
| Curosurf LISA | Efficacy: Blood Gas Analysis Parameters -- Partial Pressure of Carbon Dioxide (pCO2) | 72 h - post procedure (Change from pre-procedure to 72 hour post-procedure) | -2.92 mmHg |
| Curosurf Endotracheal Tube | Efficacy: Blood Gas Analysis Parameters -- Partial Pressure of Carbon Dioxide (pCO2) | 48 h - post procedure (Change from pre-procedure to 48 hour post-procedure) | -5.64 mmHg |
| Curosurf Endotracheal Tube | Efficacy: Blood Gas Analysis Parameters -- Partial Pressure of Carbon Dioxide (pCO2) | Pre-procedure (actual value) | 52.34 mmHg |
| Curosurf Endotracheal Tube | Efficacy: Blood Gas Analysis Parameters -- Partial Pressure of Carbon Dioxide (pCO2) | 24 h - post procedure (Change from pre-procedure to 24 hour post-procedure) | -7.93 mmHg |
| Curosurf Endotracheal Tube | Efficacy: Blood Gas Analysis Parameters -- Partial Pressure of Carbon Dioxide (pCO2) | 1 h - post procedure (Change from pre-procedure to 1 hour post-procedure) | -0.85 mmHg |
| Curosurf Endotracheal Tube | Efficacy: Blood Gas Analysis Parameters -- Partial Pressure of Carbon Dioxide (pCO2) | 72 h - post procedure (Change from pre-procedure to 72 hour post-procedure) | -5.24 mmHg |
| Curosurf Endotracheal Tube | Efficacy: Blood Gas Analysis Parameters -- Partial Pressure of Carbon Dioxide (pCO2) | 6 h - post procedure (Change from pre-procedure to 6 hour post-procedure) | -2.26 mmHg |
Secondary
Efficacy: Blood Gas Analysis Parameters -- Partial Pressure of Oxygen (pO2)
The blood gas analysis partial pressure of oxygen (pO2) at all timepoints and the changes from pre-procedure to each timepoint are presented.
Time frame: First 72 hours of life (1h, 6h, 24h, 48h, 72h)
Population: Intention-to-treat population (ITT): All randomized neonates who received at least one dose of study treatment.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Curosurf LISA | Efficacy: Blood Gas Analysis Parameters -- Partial Pressure of Oxygen (pO2) | Pre-procedure (actual value) | 54.78 mmHg |
| Curosurf LISA | Efficacy: Blood Gas Analysis Parameters -- Partial Pressure of Oxygen (pO2) | 1 h - post procedure (Change from pre-procedure to 1 hour post-procedure) | 4.22 mmHg |
| Curosurf LISA | Efficacy: Blood Gas Analysis Parameters -- Partial Pressure of Oxygen (pO2) | 6 h - post procedure (Change from pre-procedure to 6 hour post-procedure) | 2.69 mmHg |
| Curosurf LISA | Efficacy: Blood Gas Analysis Parameters -- Partial Pressure of Oxygen (pO2) | 24 h - post procedure (Change from pre-procedure to 24 hour post-procedure) | -5.74 mmHg |
| Curosurf LISA | Efficacy: Blood Gas Analysis Parameters -- Partial Pressure of Oxygen (pO2) | 48 h - post procedure (Change from pre-procedure to 48 hour post-procedure) | -7.51 mmHg |
| Curosurf LISA | Efficacy: Blood Gas Analysis Parameters -- Partial Pressure of Oxygen (pO2) | 72 h - post procedure (Change from pre-procedure to 72 hour post-procedure) | -5.01 mmHg |
| Curosurf Endotracheal Tube | Efficacy: Blood Gas Analysis Parameters -- Partial Pressure of Oxygen (pO2) | 48 h - post procedure (Change from pre-procedure to 48 hour post-procedure) | -8.07 mmHg |
| Curosurf Endotracheal Tube | Efficacy: Blood Gas Analysis Parameters -- Partial Pressure of Oxygen (pO2) | Pre-procedure (actual value) | 58.51 mmHg |
| Curosurf Endotracheal Tube | Efficacy: Blood Gas Analysis Parameters -- Partial Pressure of Oxygen (pO2) | 24 h - post procedure (Change from pre-procedure to 24 hour post-procedure) | 0.84 mmHg |
| Curosurf Endotracheal Tube | Efficacy: Blood Gas Analysis Parameters -- Partial Pressure of Oxygen (pO2) | 1 h - post procedure (Change from pre-procedure to 1 hour post-procedure) | 2.34 mmHg |
| Curosurf Endotracheal Tube | Efficacy: Blood Gas Analysis Parameters -- Partial Pressure of Oxygen (pO2) | 72 h - post procedure (Change from pre-procedure to 72 hour post-procedure) | -2.25 mmHg |
| Curosurf Endotracheal Tube | Efficacy: Blood Gas Analysis Parameters -- Partial Pressure of Oxygen (pO2) | 6 h - post procedure (Change from pre-procedure to 6 hour post-procedure) | -0.06 mmHg |
Secondary
Efficacy: Blood Gas Analysis Parameters -- pH
The blood gas analysis for blood pH at all timepoints and the changes from pre-procedure to each timepoint are presented. Results for pH values are based on a scale of 0 to 14. A pH value of 7 is neutral, pH less than 7 is acidic, and pH greater than 7 is basic.
Time frame: First 72 hours of life (1h, 6h, 24h, 48h, 72h)
Population: Intention-to-treat population (ITT): All randomized neonates who received at least one dose of study treatment.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Curosurf LISA | Efficacy: Blood Gas Analysis Parameters -- pH | Pre-procedure (actual value) | 7.289 units on a pH scale |
| Curosurf LISA | Efficacy: Blood Gas Analysis Parameters -- pH | 1 h - post procedure (Change from pre-procedure to 1 hour post-procedure) | 0.016 units on a pH scale |
| Curosurf LISA | Efficacy: Blood Gas Analysis Parameters -- pH | 6 h - post procedure (Change from pre-procedure to 6 hour post-procedure) | 0.044 units on a pH scale |
| Curosurf LISA | Efficacy: Blood Gas Analysis Parameters -- pH | 24 h - post procedure (Change from pre-procedure to 24 hour post-procedure) | 0.038 units on a pH scale |
| Curosurf LISA | Efficacy: Blood Gas Analysis Parameters -- pH | 48 h - post procedure (Change from pre-procedure to 48 hour post-procedure) | 0.008 units on a pH scale |
| Curosurf LISA | Efficacy: Blood Gas Analysis Parameters -- pH | 72 h - post procedure (Change from pre-procedure to 72 hour post-procedure) | 0.001 units on a pH scale |
| Curosurf Endotracheal Tube | Efficacy: Blood Gas Analysis Parameters -- pH | 48 h - post procedure (Change from pre-procedure to 48 hour post-procedure) | 0.072 units on a pH scale |
| Curosurf Endotracheal Tube | Efficacy: Blood Gas Analysis Parameters -- pH | Pre-procedure (actual value) | 7.240 units on a pH scale |
| Curosurf Endotracheal Tube | Efficacy: Blood Gas Analysis Parameters -- pH | 24 h - post procedure (Change from pre-procedure to 24 hour post-procedure) | 0.082 units on a pH scale |
| Curosurf Endotracheal Tube | Efficacy: Blood Gas Analysis Parameters -- pH | 1 h - post procedure (Change from pre-procedure to 1 hour post-procedure) | 0.038 units on a pH scale |
| Curosurf Endotracheal Tube | Efficacy: Blood Gas Analysis Parameters -- pH | 72 h - post procedure (Change from pre-procedure to 72 hour post-procedure) | 0.068 units on a pH scale |
| Curosurf Endotracheal Tube | Efficacy: Blood Gas Analysis Parameters -- pH | 6 h - post procedure (Change from pre-procedure to 6 hour post-procedure) | 0.047 units on a pH scale |
Secondary
Efficacy: Duration of Invasive Mechanical Ventilation During the Study
The duration of invasive ventilation (MV) in the first 72 hours of life and respective statistical analyses, are presented by treatment group.
Time frame: First 72 hours of life
Population: Intention-to-treat population (ITT): All randomized neonates who received at least one dose of study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Curosurf LISA | Efficacy: Duration of Invasive Mechanical Ventilation During the Study | 29.8 hours |
| Curosurf Endotracheal Tube | Efficacy: Duration of Invasive Mechanical Ventilation During the Study | 61.4 hours |
Comparison: Duration of invasive mechanical ventilation.p-value: 0.59695% CI: [-120.9, 63.6]Wilcoxon (Mann-Whitney)
Secondary
Efficacy: Duration of Oxygen Alone Supplementation and Any Non-Invasive Ventilation (NIV)
The duration of oxygen alone supplementation and any non-invasive ventilation (NIV) during the study are presented by treatment group. PMA=Post-Menstrual Age PNA=Post-Natal Age
Time frame: First 72 hours of life, Up to 28 days Post-Natal Age (PNA), Up to 36 weeks Post-Menstrual Age (PMA).
Population: Intention-to-treat population (ITT): All randomized neonates who received at least one dose of study treatment.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Curosurf LISA | Efficacy: Duration of Oxygen Alone Supplementation and Any Non-Invasive Ventilation (NIV) | Duration of standalone oxygen supplementation | 16.4 days |
| Curosurf LISA | Efficacy: Duration of Oxygen Alone Supplementation and Any Non-Invasive Ventilation (NIV) | Duration of NIV | 45.7 days |
| Curosurf Endotracheal Tube | Efficacy: Duration of Oxygen Alone Supplementation and Any Non-Invasive Ventilation (NIV) | Duration of standalone oxygen supplementation | 16.4 days |
| Curosurf Endotracheal Tube | Efficacy: Duration of Oxygen Alone Supplementation and Any Non-Invasive Ventilation (NIV) | Duration of NIV | 38.3 days |
Comparison: Duration of standalone oxygen supplementationp-value: 0.56395% CI: [-13.8, 23.8]Wilcoxon (Mann-Whitney)
Comparison: Duration of NIVp-value: 0.61295% CI: [-19.7, 21.7]Wilcoxon (Mann-Whitney)
Secondary
Efficacy: Fraction of Inspired Oxygen (FiO2)
The FiO2 values at timepoints up to and including 120 hours post-treatment and the changes from pre-procedure to each of those timepoints are presented by treatment group. The fraction of inspired oxygen (FiO2) is the concentration of oxygen in the gas mixture.
Time frame: Pre-procedure, at time 0 (T0, end of surfactant instillation) and post treatment after T0 at 5, 15, 30 minutes, at 1, 6, 12, 24, 48, 72, and 120 hours, on Day 28 PNA, 36 weeks PMA.
Population: Intention-to-treat population (ITT): All randomized neonates who received at least one dose of study treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Curosurf LISA | Efficacy: Fraction of Inspired Oxygen (FiO2) | Pre-procedure | 0.435 fraction of inspired oxygen | Standard Deviation 0.151 |
| Curosurf LISA | Efficacy: Fraction of Inspired Oxygen (FiO2) | T0 | 0.569 fraction of inspired oxygen | Standard Deviation 0.252 |
| Curosurf LISA | Efficacy: Fraction of Inspired Oxygen (FiO2) | 5 mins | 0.365 fraction of inspired oxygen | Standard Deviation 0.197 |
| Curosurf LISA | Efficacy: Fraction of Inspired Oxygen (FiO2) | 15 mins | 0.321 fraction of inspired oxygen | Standard Deviation 0.199 |
| Curosurf LISA | Efficacy: Fraction of Inspired Oxygen (FiO2) | 30 mins | 0.257 fraction of inspired oxygen | Standard Deviation 0.09 |
| Curosurf LISA | Efficacy: Fraction of Inspired Oxygen (FiO2) | 1 hour | 0.251 fraction of inspired oxygen | Standard Deviation 0.108 |
| Curosurf LISA | Efficacy: Fraction of Inspired Oxygen (FiO2) | 6 hours | 0.244 fraction of inspired oxygen | Standard Deviation 0.077 |
| Curosurf LISA | Efficacy: Fraction of Inspired Oxygen (FiO2) | 12 hours | 0.246 fraction of inspired oxygen | Standard Deviation 0.075 |
| Curosurf LISA | Efficacy: Fraction of Inspired Oxygen (FiO2) | 24 hours | 0.238 fraction of inspired oxygen | Standard Deviation 0.064 |
| Curosurf LISA | Efficacy: Fraction of Inspired Oxygen (FiO2) | 48 hours | 0.239 fraction of inspired oxygen | Standard Deviation 0.033 |
| Curosurf LISA | Efficacy: Fraction of Inspired Oxygen (FiO2) | 72 hours | 0.257 fraction of inspired oxygen | Standard Deviation 0.088 |
| Curosurf LISA | Efficacy: Fraction of Inspired Oxygen (FiO2) | 120 hours | 0.237 fraction of inspired oxygen | Standard Deviation 0.049 |
| Curosurf LISA | Efficacy: Fraction of Inspired Oxygen (FiO2) | Day 28 PNA | 0.285 fraction of inspired oxygen | Standard Deviation 0.188 |
| Curosurf LISA | Efficacy: Fraction of Inspired Oxygen (FiO2) | 36 weeks PMA | 0.270 fraction of inspired oxygen | Standard Deviation 0.029 |
| Curosurf Endotracheal Tube | Efficacy: Fraction of Inspired Oxygen (FiO2) | 72 hours | 0.262 fraction of inspired oxygen | Standard Deviation 0.099 |
| Curosurf Endotracheal Tube | Efficacy: Fraction of Inspired Oxygen (FiO2) | Pre-procedure | 0.524 fraction of inspired oxygen | Standard Deviation 0.235 |
| Curosurf Endotracheal Tube | Efficacy: Fraction of Inspired Oxygen (FiO2) | 12 hours | 0.290 fraction of inspired oxygen | Standard Deviation 0.225 |
| Curosurf Endotracheal Tube | Efficacy: Fraction of Inspired Oxygen (FiO2) | T0 | 0.475 fraction of inspired oxygen | Standard Deviation 0.25 |
| Curosurf Endotracheal Tube | Efficacy: Fraction of Inspired Oxygen (FiO2) | Day 28 PNA | 0.272 fraction of inspired oxygen | Standard Deviation 0.091 |
| Curosurf Endotracheal Tube | Efficacy: Fraction of Inspired Oxygen (FiO2) | 5 mins | 0.457 fraction of inspired oxygen | Standard Deviation 0.26 |
| Curosurf Endotracheal Tube | Efficacy: Fraction of Inspired Oxygen (FiO2) | 24 hours | 0.269 fraction of inspired oxygen | Standard Deviation 0.113 |
| Curosurf Endotracheal Tube | Efficacy: Fraction of Inspired Oxygen (FiO2) | 15 mins | 0.373 fraction of inspired oxygen | Standard Deviation 0.186 |
| Curosurf Endotracheal Tube | Efficacy: Fraction of Inspired Oxygen (FiO2) | 120 hours | 0.243 fraction of inspired oxygen | Standard Deviation 0.099 |
| Curosurf Endotracheal Tube | Efficacy: Fraction of Inspired Oxygen (FiO2) | 30 mins | 0.372 fraction of inspired oxygen | Standard Deviation 0.258 |
| Curosurf Endotracheal Tube | Efficacy: Fraction of Inspired Oxygen (FiO2) | 48 hours | 0.285 fraction of inspired oxygen | Standard Deviation 0.133 |
| Curosurf Endotracheal Tube | Efficacy: Fraction of Inspired Oxygen (FiO2) | 1 hour | 0.279 fraction of inspired oxygen | Standard Deviation 0.084 |
| Curosurf Endotracheal Tube | Efficacy: Fraction of Inspired Oxygen (FiO2) | 36 weeks PMA | 0.254 fraction of inspired oxygen | Standard Deviation 0.033 |
| Curosurf Endotracheal Tube | Efficacy: Fraction of Inspired Oxygen (FiO2) | 6 hours | 0.274 fraction of inspired oxygen | Standard Deviation 0.131 |
Comparison: T0, Treatment comparison. The analysis was based on an MMRM with treatment, timepoint, treatment by timepoint interaction, and GA group as fixed effects and pre-procedure FiO2 as a covariate.p-value: 0.5995% CI: [-0.141, 0.243]Mixed model for repeated measures
Comparison: 5 min, Treatment comparison. The analysis was based on an MMRM with treatment, timepoint, treatment by timepoint interaction, and GA group as fixed effects and pre-procedure FiO2 as a covariate.p-value: 0.51195% CI: [-0.21, 0.107]Mixed model for repeated measures
Comparison: 15 min, Treatment comparison. The analysis was based on an MMRM with treatment, timepoint, treatment by timepoint interaction, and GA group as fixed effects and pre-procedure FiO2 as a covariate.p-value: 0.48895% CI: [-0.196, 0.096]Mixed model for repeated measures
Comparison: 30 min, Treatment comparison. The analysis was based on an MMRM with treatment, timepoint, treatment by timepoint interaction, and GA group as fixed effects and pre-procedure FiO2 as a covariate.p-value: 0.09195% CI: [-0.239, 0.019]Mixed model for repeated measures
Comparison: 1 hour, Treatment comparison. The analysis was based on an MMRM with treatment, timepoint, treatment by timepoint interaction, and GA group as fixed effects and pre-procedure FiO2 as a covariate.p-value: 0.34495% CI: [-0.076, 0.027]Mixed model for repeated measures
Comparison: 6 hours, Treatment comparison. The analysis was based on an MMRM with treatment, timepoint, treatment by timepoint interaction, and GA group as fixed effects and pre-procedure FiO2 as a covariate.p-value: 0.37695% CI: [-0.084, 0.033]Mixed model for repeated measures
Comparison: 12 hours, Treatment comparison. The analysis was based on an MMRM with treatment, timepoint, treatment by timepoint interaction, and GA group as fixed effects and pre-procedure FiO2 as a covariate.p-value: 0.39695% CI: [-0.135, 0.055]Mixed model for repeated measures
Comparison: 24 hours, Treatment comparison. The analysis was based on an MMRM with treatment, timepoint, treatment by timepoint interaction, and GA group as fixed effects and pre-procedure FiO2 as a covariate.p-value: 0.26895% CI: [-0.074, 0.021]Mixed model for repeated measures
Comparison: 48 hours, Treatment comparison. The analysis was based on an MMRM with treatment, timepoint, treatment by timepoint interaction, and GA group as fixed effects and pre-procedure FiO2 as a covariate.p-value: 0.14795% CI: [-0.089, 0.014]Mixed model for repeated measures
Comparison: 72 hours, Treatment comparison. The analysis was based on an MMRM with treatment, timepoint, treatment by timepoint interaction, and GA group as fixed effects and pre-procedure FiO2 as a covariate.p-value: 0.99495% CI: [-0.055, 0.055]Mixed model for repeated measures
Comparison: 120 hours, Treatment comparison. The analysis was based on an MMRM with treatment, timepoint, treatment by timepoint interaction, and GA group as fixed effects and pre-procedure FiO2 as a covariate.p-value: 0.85395% CI: [-0.048, 0.04]Mixed model for repeated measures
Secondary
Efficacy: Median Duration of Invasive Mechanical Ventilation During the Study
The duration of invasive ventilation (MV) in the first 28 days PNA, and within 36 weeks PMA, are presented by treatment group. Participants who actually received invasive ventilation are reported in the table below.
Time frame: Up to 28 days PNA, Up to 36 weeks PMA
Population: Intention-to-treat population (ITT): All randomized neonates who received at least one dose of study treatment.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Curosurf LISA | Efficacy: Median Duration of Invasive Mechanical Ventilation During the Study | Duration of invasive MV in first 28 days PNA | 6.0 days |
| Curosurf LISA | Efficacy: Median Duration of Invasive Mechanical Ventilation During the Study | Duration of invasive MV within 36 weeks PMA | 6 days |
| Curosurf Endotracheal Tube | Efficacy: Median Duration of Invasive Mechanical Ventilation During the Study | Duration of invasive MV in first 28 days PNA | 20.5 days |
| Curosurf Endotracheal Tube | Efficacy: Median Duration of Invasive Mechanical Ventilation During the Study | Duration of invasive MV within 36 weeks PMA | 24 days |
Comparison: Duration of invasive MV in first 28 days PNA.p-value: 0.33395% CI: [-32.3, 16.3]Wilcoxon (Mann-Whitney)
Comparison: Duration of invasive MV within 36 weeks PMA.p-value: 0.33495% CI: [-49.5, 33.5]Wilcoxon (Mann-Whitney)
Secondary
Efficacy: Neonates Needing Additional 2 or 3 Doses of Surfactant
A summary of the percentage of neonates requiring at least one additional dose of surfactant, and respective statistical analysis, is presented by treatment group i.e. 2 or 3 doses of surfactant .
Time frame: First 72 hours of life.
Population: Intention-to-treat population (ITT): All randomized neonates who received at least one dose of study treatment.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Curosurf LISA | Efficacy: Neonates Needing Additional 2 or 3 Doses of Surfactant | Additional dose of surfactant (n=2 doses) | 4 Participants |
| Curosurf LISA | Efficacy: Neonates Needing Additional 2 or 3 Doses of Surfactant | Additional dose of surfactant (n=3 doses) | 2 Participants |
| Curosurf Endotracheal Tube | Efficacy: Neonates Needing Additional 2 or 3 Doses of Surfactant | Additional dose of surfactant (n=2 doses) | 2 Participants |
| Curosurf Endotracheal Tube | Efficacy: Neonates Needing Additional 2 or 3 Doses of Surfactant | Additional dose of surfactant (n=3 doses) | 1 Participants |
Secondary
Efficacy: Neonates Needing Additional Surfactant Doses
A summary of the percentage of neonates requiring at least one additional dose of surfactant, and respective statistical analysis, is presented by treatment group.
Time frame: First 72 hours of life.
Population: Intention-to-treat population (ITT): All randomized neonates who received at least one dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Curosurf LISA | Efficacy: Neonates Needing Additional Surfactant Doses | 6 Participants |
| Curosurf Endotracheal Tube | Efficacy: Neonates Needing Additional Surfactant Doses | 3 Participants |
Secondary
Efficacy: Percentage of Neonates Needing Any Intubation Procedure, Outside the Initial Surfactant Administration Period
The percentage of neonates needing any intubation procedure, outside the initial surfactant administration period (i.e., excluding endotracheal intubation\[s\] that were required for surfactant administration in the Conventional administration arm), in the first 72 hours of life, in the first 28 days post-natal age (PNA), and within 36 weeks Post-menstrual age (PMA), and respective statistical analyses, are presented.
Time frame: First 72 hours of life, up to 28 days post-natal age (PNA), Up to 36 weeks Post-menstrual age (PMA)
Population: Intention-to-treat population (ITT): All randomized neonates who received at least one dose of study treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Curosurf LISA | Efficacy: Percentage of Neonates Needing Any Intubation Procedure, Outside the Initial Surfactant Administration Period | Any intubation procedure in first 72 hours of life. | 10.5 percentage of participants |
| Curosurf LISA | Efficacy: Percentage of Neonates Needing Any Intubation Procedure, Outside the Initial Surfactant Administration Period | Any intubation procedure in first 28 days PNA | 31.6 percentage of participants |
| Curosurf LISA | Efficacy: Percentage of Neonates Needing Any Intubation Procedure, Outside the Initial Surfactant Administration Period | Any intubation procedure within 36 weeks PMA | 31.6 percentage of participants |
| Curosurf Endotracheal Tube | Efficacy: Percentage of Neonates Needing Any Intubation Procedure, Outside the Initial Surfactant Administration Period | Any intubation procedure in first 72 hours of life. | 25.0 percentage of participants |
| Curosurf Endotracheal Tube | Efficacy: Percentage of Neonates Needing Any Intubation Procedure, Outside the Initial Surfactant Administration Period | Any intubation procedure in first 28 days PNA | 25.0 percentage of participants |
| Curosurf Endotracheal Tube | Efficacy: Percentage of Neonates Needing Any Intubation Procedure, Outside the Initial Surfactant Administration Period | Any intubation procedure within 36 weeks PMA | 25.0 percentage of participants |
Comparison: Any intubation procedure in first 72 hours of life.p-value: 0.2295% CI: [-39.6, 8.2]Cochran-Mantel-Haenszel
Comparison: Any intubation procedure within 36 weeks PMA.p-value: 0.74195% CI: [-22.8, 32.5]Cochran-Mantel-Haenszel
Secondary
Efficacy: Percentage of Neonates Needing Invasive Mechanical Ventilation (MV) During the Study
The percentage of neonates needing invasive mechanical ventilation (MV) in the first 72 hours of life, in the first 28 days post-natal age (PNA), and within 36 weeks Post-Menstrual Age (PMA), and respective statistical analyses, are presented by treatment group.
Time frame: First 72 hours of life, Up to 28 days Post-Natal Age (PNA), Up to 36 weeks PMA
Population: Intention-to-treat population (ITT): All randomized neonates who received at least one dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Curosurf LISA | Efficacy: Percentage of Neonates Needing Invasive Mechanical Ventilation (MV) During the Study | Invasive MV in first 72 hours of life. | 3 Participants |
| Curosurf LISA | Efficacy: Percentage of Neonates Needing Invasive Mechanical Ventilation (MV) During the Study | Invasive MV in first 28 days PNA. | 6 Participants |
| Curosurf LISA | Efficacy: Percentage of Neonates Needing Invasive Mechanical Ventilation (MV) During the Study | Invasive MV within 36 weeks PMA. | 6 Participants |
| Curosurf Endotracheal Tube | Efficacy: Percentage of Neonates Needing Invasive Mechanical Ventilation (MV) During the Study | Invasive MV in first 72 hours of life. | 4 Participants |
| Curosurf Endotracheal Tube | Efficacy: Percentage of Neonates Needing Invasive Mechanical Ventilation (MV) During the Study | Invasive MV in first 28 days PNA. | 4 Participants |
| Curosurf Endotracheal Tube | Efficacy: Percentage of Neonates Needing Invasive Mechanical Ventilation (MV) During the Study | Invasive MV within 36 weeks PMA. | 4 Participants |
Comparison: Invasive MV in the first 72 hours of life.p-value: 0.21995% CI: [-47, 9.8]Cochran-Mantel-Haenszel
Comparison: Invasive MV in first 28 days PNAp-value: 0.82695% CI: [-33.5, 26.7]Cochran-Mantel-Haenszel
Comparison: Invasive MV within 36 weeks PMA.p-value: 0.82695% CI: [-33.5, 26.7]Cochran-Mantel-Haenszel
Secondary
Efficacy: Preductal Oxygen Saturation/Fraction of Inspired Oxygen (SpO2/FiO2) Ratio
The mean SpO2/FiO2 ratio values at timepoints up to and including 120 hours post-treatment, and respective statistical analyses, are summarized by treatment group.
Time frame: Pre-procedure, at time 0 (T0, end of surfactant instillation) and post treatment after T0 at 5, 15, 30 minutes, at 1, 6, 12, 24, 48, 72, and 120 hours, on Day 28 PNA, 36 weeks PMA.
Population: Intention-to-treat population (ITT): All randomized neonates who received at least one dose of study treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Curosurf LISA | Efficacy: Preductal Oxygen Saturation/Fraction of Inspired Oxygen (SpO2/FiO2) Ratio | 15 mins | 3.438 ratio | Standard Deviation 1.116 |
| Curosurf LISA | Efficacy: Preductal Oxygen Saturation/Fraction of Inspired Oxygen (SpO2/FiO2) Ratio | 12 hours | 4.090 ratio | Standard Deviation 0.811 |
| Curosurf LISA | Efficacy: Preductal Oxygen Saturation/Fraction of Inspired Oxygen (SpO2/FiO2) Ratio | Pre-procedure | 2.368 ratio | Standard Deviation 0.794 |
| Curosurf LISA | Efficacy: Preductal Oxygen Saturation/Fraction of Inspired Oxygen (SpO2/FiO2) Ratio | 24 hours | 4.139 ratio | Standard Deviation 0.73 |
| Curosurf LISA | Efficacy: Preductal Oxygen Saturation/Fraction of Inspired Oxygen (SpO2/FiO2) Ratio | 30 mins | 3.960 ratio | Standard Deviation 0.875 |
| Curosurf LISA | Efficacy: Preductal Oxygen Saturation/Fraction of Inspired Oxygen (SpO2/FiO2) Ratio | 48 hours | 4.046 ratio | Standard Deviation 0.568 |
| Curosurf LISA | Efficacy: Preductal Oxygen Saturation/Fraction of Inspired Oxygen (SpO2/FiO2) Ratio | 5 mins | 3.113 ratio | Standard Deviation 1.164 |
| Curosurf LISA | Efficacy: Preductal Oxygen Saturation/Fraction of Inspired Oxygen (SpO2/FiO2) Ratio | 72 hours | 3.988 ratio | Standard Deviation 0.887 |
| Curosurf LISA | Efficacy: Preductal Oxygen Saturation/Fraction of Inspired Oxygen (SpO2/FiO2) Ratio | 120 hours | 4.205 ratio | Standard Deviation 0.698 |
| Curosurf LISA | Efficacy: Preductal Oxygen Saturation/Fraction of Inspired Oxygen (SpO2/FiO2) Ratio | 1 hour | 4.106 ratio | Standard Deviation 0.869 |
| Curosurf LISA | Efficacy: Preductal Oxygen Saturation/Fraction of Inspired Oxygen (SpO2/FiO2) Ratio | Day 28 PNA | 3.975 ratio | Standard Deviation 1.104 |
| Curosurf LISA | Efficacy: Preductal Oxygen Saturation/Fraction of Inspired Oxygen (SpO2/FiO2) Ratio | T0 | 1.796 ratio | Standard Deviation 1.035 |
| Curosurf LISA | Efficacy: Preductal Oxygen Saturation/Fraction of Inspired Oxygen (SpO2/FiO2) Ratio | 36 weeks PMA | 3.571 ratio | Standard Deviation 0.535 |
| Curosurf LISA | Efficacy: Preductal Oxygen Saturation/Fraction of Inspired Oxygen (SpO2/FiO2) Ratio | 6 hours | 4.152 ratio | Standard Deviation 0.776 |
| Curosurf Endotracheal Tube | Efficacy: Preductal Oxygen Saturation/Fraction of Inspired Oxygen (SpO2/FiO2) Ratio | 36 weeks PMA | 3.840 ratio | Standard Deviation 0.599 |
| Curosurf Endotracheal Tube | Efficacy: Preductal Oxygen Saturation/Fraction of Inspired Oxygen (SpO2/FiO2) Ratio | Pre-procedure | 2.052 ratio | Standard Deviation 0.659 |
| Curosurf Endotracheal Tube | Efficacy: Preductal Oxygen Saturation/Fraction of Inspired Oxygen (SpO2/FiO2) Ratio | T0 | 2.463 ratio | Standard Deviation 1.221 |
| Curosurf Endotracheal Tube | Efficacy: Preductal Oxygen Saturation/Fraction of Inspired Oxygen (SpO2/FiO2) Ratio | 5 mins | 2.657 ratio | Standard Deviation 1.376 |
| Curosurf Endotracheal Tube | Efficacy: Preductal Oxygen Saturation/Fraction of Inspired Oxygen (SpO2/FiO2) Ratio | 15 mins | 3.010 ratio | Standard Deviation 1.229 |
| Curosurf Endotracheal Tube | Efficacy: Preductal Oxygen Saturation/Fraction of Inspired Oxygen (SpO2/FiO2) Ratio | 30 mins | 3.253 ratio | Standard Deviation 1.358 |
| Curosurf Endotracheal Tube | Efficacy: Preductal Oxygen Saturation/Fraction of Inspired Oxygen (SpO2/FiO2) Ratio | 1 hour | 3.577 ratio | Standard Deviation 0.921 |
| Curosurf Endotracheal Tube | Efficacy: Preductal Oxygen Saturation/Fraction of Inspired Oxygen (SpO2/FiO2) Ratio | 6 hours | 3.919 ratio | Standard Deviation 1.061 |
| Curosurf Endotracheal Tube | Efficacy: Preductal Oxygen Saturation/Fraction of Inspired Oxygen (SpO2/FiO2) Ratio | 12 hours | 3.976 ratio | Standard Deviation 1.172 |
| Curosurf Endotracheal Tube | Efficacy: Preductal Oxygen Saturation/Fraction of Inspired Oxygen (SpO2/FiO2) Ratio | 24 hours | 3.829 ratio | Standard Deviation 0.945 |
| Curosurf Endotracheal Tube | Efficacy: Preductal Oxygen Saturation/Fraction of Inspired Oxygen (SpO2/FiO2) Ratio | 48 hours | 3.653 ratio | Standard Deviation 0.952 |
| Curosurf Endotracheal Tube | Efficacy: Preductal Oxygen Saturation/Fraction of Inspired Oxygen (SpO2/FiO2) Ratio | 120 hours | 4.263 ratio | Standard Deviation 0.862 |
| Curosurf Endotracheal Tube | Efficacy: Preductal Oxygen Saturation/Fraction of Inspired Oxygen (SpO2/FiO2) Ratio | Day 28 PNA | 3.804 ratio | Standard Deviation 0.936 |
| Curosurf Endotracheal Tube | Efficacy: Preductal Oxygen Saturation/Fraction of Inspired Oxygen (SpO2/FiO2) Ratio | 72 hours | 3.916 ratio | Standard Deviation 0.944 |
Comparison: T0, Treatment comparison. The analysis was based on an mixed model for repeated measures (MMRM) with treatment, timepoint, treatment by timepoint interaction, and GA group as fixed effects and pre-procedure SpO2/FiO2 as a covariate.p-value: 0.13795% CI: [-1.447, 0.21]Mixed model for repeated measures
Comparison: 5 min, Treatment comparison. The analysis was based on an MMRM with treatment, timepoint, treatment by timepoint interaction, and GA group as fixed effects and pre-procedure SpO2/FiO2 as a covariate.p-value: 0.53495% CI: [-0.604, 1.14]Mixed model for repeated measures
Comparison: 15 min, Treatment comparison. The analysis was based on an MMRM with treatment, timepoint, treatment by timepoint interaction, and GA group as fixed effects and pre-procedure SpO2/FiO2 as a covariate.p-value: 0.5395% CI: [-0.597, 1.136]Mixed model for repeated measures
Comparison: 30 min, Treatment comparison. The analysis was based on an MMRM with treatment, timepoint, treatment by timepoint interaction, and GA group as fixed effects and pre-procedure SpO2/FiO2 as a covariate.p-value: 0.09195% CI: [-0.108, 1.389]Mixed model for repeated measures
Comparison: 1 hour, Treatment comparison. The analysis was based on an MMRM with treatment, timepoint, treatment by timepoint interaction, and GA group as fixed effects and pre-procedure SpO2/FiO2 as a covariate.p-value: 0.0495% CI: [0.023, 0.903]Mixed model for repeated measures
Comparison: 6 hours, Treatment comparison. The analysis was based on an MMRM with treatment, timepoint, treatment by timepoint interaction, and GA group as fixed effects and pre-procedure SpO2/FiO2 as a covariate.p-value: 0.53295% CI: [-0.371, 0.703]Mixed model for repeated measures
Comparison: 12 hours, Treatment comparison. The analysis was based on an MMRM with treatment, timepoint, treatment by timepoint interaction, and GA group as fixed effects and pre-procedure SpO2/FiO2 as a covariate.p-value: 0.87795% CI: [-0.578, 0.674]Mixed model for repeated measures
Comparison: 24 hours, Treatment comparison. The analysis was based on an MMRM with treatment, timepoint, treatment by timepoint interaction, and GA group as fixed effects and pre-procedure SpO2/FiO2 as a covariate.p-value: 0.35695% CI: [-0.289, 0.776]Mixed model for repeated measures
Comparison: 48 hours, Treatment comparison. The analysis was based on an MMRM with treatment, timepoint, treatment by timepoint interaction, and GA group as fixed effects and pre-procedure SpO2/FiO2 as a covariate.p-value: 0.25895% CI: [-0.235, 0.841]Mixed model for repeated measures
Comparison: 72 hours, Treatment comparison. The analysis was based on an MMRM with treatment, timepoint, treatment by timepoint interaction, and GA group as fixed effects and pre-procedure SpO2/FiO2 as a covariate.p-value: 0.94595% CI: [-0.616, 0.66]Mixed model for repeated measures
Comparison: 120 hours, Treatment comparison. The analysis was based on an MMRM with treatment, timepoint, treatment by timepoint interaction, and GA group as fixed effects and pre-procedure SpO2/FiO2 as a covariate.p-value: 0.76695% CI: [-0.586, 0.436]Mixed model for repeated measures
Secondary
Efficacy: Preductal Oxygen Saturation (SpO2)
The mean SpO2 values at timepoints up to and including 120 hours post-treatment are summarized by treatment group. Oxygen saturation (SpO2) is a measurement of how much oxygen the blood is carrying as a percentage of the maximum it could carry.
Time frame: Pre-procedure, at time 0 (T0, end of surfactant instillation) and post treatment after T0 at 5, 15, 30 minutes, at 1, 6, 12, 24, 48, 72, and 120 hours, on Day 28 PNA, 36 weeks PMA.
Population: Intention-to-treat population (ITT): All randomized neonates who received at least one dose of study treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Curosurf LISA | Efficacy: Preductal Oxygen Saturation (SpO2) | Pre-procedure | 92.7 percentage of oxygen saturation | Standard Deviation 3 |
| Curosurf LISA | Efficacy: Preductal Oxygen Saturation (SpO2) | T0 | 81.1 percentage of oxygen saturation | Standard Deviation 17.9 |
| Curosurf LISA | Efficacy: Preductal Oxygen Saturation (SpO2) | 5 mins | 94.6 percentage of oxygen saturation | Standard Deviation 7.6 |
| Curosurf LISA | Efficacy: Preductal Oxygen Saturation (SpO2) | 15 mins | 92.8 percentage of oxygen saturation | Standard Deviation 9.6 |
| Curosurf LISA | Efficacy: Preductal Oxygen Saturation (SpO2) | 30 mins | 95.0 percentage of oxygen saturation | Standard Deviation 4.1 |
| Curosurf LISA | Efficacy: Preductal Oxygen Saturation (SpO2) | 1 hour | 94.5 percentage of oxygen saturation | Standard Deviation 4.8 |
| Curosurf LISA | Efficacy: Preductal Oxygen Saturation (SpO2) | 6 hours | 96.1 percentage of oxygen saturation | Standard Deviation 2.6 |
| Curosurf LISA | Efficacy: Preductal Oxygen Saturation (SpO2) | 12 hours | 94.9 percentage of oxygen saturation | Standard Deviation 3.1 |
| Curosurf LISA | Efficacy: Preductal Oxygen Saturation (SpO2) | 24 hours | 94.5 percentage of oxygen saturation | Standard Deviation 3.6 |
| Curosurf LISA | Efficacy: Preductal Oxygen Saturation (SpO2) | 48 hours | 95.2 percentage of oxygen saturation | Standard Deviation 2.9 |
| Curosurf LISA | Efficacy: Preductal Oxygen Saturation (SpO2) | 72 hours | 95.5 percentage of oxygen saturation | Standard Deviation 2.9 |
| Curosurf LISA | Efficacy: Preductal Oxygen Saturation (SpO2) | 120 hours | 96.4 percentage of oxygen saturation | Standard Deviation 2.7 |
| Curosurf LISA | Efficacy: Preductal Oxygen Saturation (SpO2) | Day 28 PNA | 96.3 percentage of oxygen saturation | Standard Deviation 3.4 |
| Curosurf LISA | Efficacy: Preductal Oxygen Saturation (SpO2) | 36 weeks PMA | 97.0 percentage of oxygen saturation | Standard Deviation 3.3 |
| Curosurf Endotracheal Tube | Efficacy: Preductal Oxygen Saturation (SpO2) | 72 hours | 93.8 percentage of oxygen saturation | Standard Deviation 3.6 |
| Curosurf Endotracheal Tube | Efficacy: Preductal Oxygen Saturation (SpO2) | Pre-procedure | 94.3 percentage of oxygen saturation | Standard Deviation 3.4 |
| Curosurf Endotracheal Tube | Efficacy: Preductal Oxygen Saturation (SpO2) | 12 hours | 91.9 percentage of oxygen saturation | Standard Deviation 14 |
| Curosurf Endotracheal Tube | Efficacy: Preductal Oxygen Saturation (SpO2) | T0 | 93.3 percentage of oxygen saturation | Standard Deviation 6.6 |
| Curosurf Endotracheal Tube | Efficacy: Preductal Oxygen Saturation (SpO2) | Day 28 PNA | 96.0 percentage of oxygen saturation | Standard Deviation 2.9 |
| Curosurf Endotracheal Tube | Efficacy: Preductal Oxygen Saturation (SpO2) | 5 mins | 93.7 percentage of oxygen saturation | Standard Deviation 7.1 |
| Curosurf Endotracheal Tube | Efficacy: Preductal Oxygen Saturation (SpO2) | 24 hours | 93.9 percentage of oxygen saturation | Standard Deviation 4.5 |
| Curosurf Endotracheal Tube | Efficacy: Preductal Oxygen Saturation (SpO2) | 15 mins | 93.5 percentage of oxygen saturation | Standard Deviation 4.7 |
| Curosurf Endotracheal Tube | Efficacy: Preductal Oxygen Saturation (SpO2) | 120 hours | 95.6 percentage of oxygen saturation | Standard Deviation 2.2 |
| Curosurf Endotracheal Tube | Efficacy: Preductal Oxygen Saturation (SpO2) | 30 mins | 91.3 percentage of oxygen saturation | Standard Deviation 10.6 |
| Curosurf Endotracheal Tube | Efficacy: Preductal Oxygen Saturation (SpO2) | 48 hours | 93.6 percentage of oxygen saturation | Standard Deviation 2.9 |
| Curosurf Endotracheal Tube | Efficacy: Preductal Oxygen Saturation (SpO2) | 1 hour | 93.0 percentage of oxygen saturation | Standard Deviation 3.7 |
| Curosurf Endotracheal Tube | Efficacy: Preductal Oxygen Saturation (SpO2) | 36 weeks PMA | 96.6 percentage of oxygen saturation | Standard Deviation 2.1 |
| Curosurf Endotracheal Tube | Efficacy: Preductal Oxygen Saturation (SpO2) | 6 hours | 94.8 percentage of oxygen saturation | Standard Deviation 2.7 |
Comparison: T0; Treatment comparison. The analysis was based on an MMRM with treatment, timepoint, treatment by timepoint interaction, and GA group as fixed effects and pre-procedure SpO2 as a covariate.p-value: 0.0995% CI: [-22.6, 1.7]Mixed model for repeated measures
Comparison: 5 min; Treatment comparison. The analysis was based on an MMRM with treatment, timepoint, treatment by timepoint interaction, and GA group as fixed effects and pre-procedure SpO2 as a covariate.p-value: 0.91795% CI: [-6.4, 5.8]Mixed model for repeated measures
Comparison: 15 min; Treatment comparison. The analysis was based on an MMRM with treatment, timepoint, treatment by timepoint interaction, and GA group as fixed effects and pre-procedure SpO2 as a covariate.p-value: 0.66895% CI: [-8.5, 5.6]Mixed model for repeated measures
Comparison: 30 min; Treatment comparison. The analysis was based on an MMRM with treatment, timepoint, treatment by timepoint interaction, and GA group as fixed effects and pre-procedure SpO2 as a covariate.p-value: 0.14995% CI: [-1.5, 9.6]Mixed model for repeated measures
Comparison: 1 hour; Treatment comparison. The analysis was based on an MMRM with treatment, timepoint, treatment by timepoint interaction, and GA group as fixed effects and pre-procedure SpO2 as a covariate.p-value: 0.31895% CI: [-1.9, 5.5]Mixed model for repeated measures
Comparison: 6 hour; Treatment comparison. The analysis was based on an MMRM with treatment, timepoint, treatment by timepoint interaction, and GA group as fixed effects and pre-procedure SpO2 as a covariate.p-value: 0.14895% CI: [-0.6, 3.7]Wilcoxon (Mann-Whitney)
Comparison: 12 hours; Treatment comparison. The analysis was based on an MMRM with treatment, timepoint, treatment by timepoint interaction, and GA group as fixed effects and pre-procedure SpO2 as a covariate.p-value: 0.33395% CI: [-3.6, 10.2]Mixed model for repeated measures
Comparison: 24 hours; Treatment comparison. The analysis was based on an MMRM with treatment, timepoint, treatment by timepoint interaction, and GA group as fixed effects and pre-procedure SpO2 as a covariate.p-value: 0.5695% CI: [-2.2, 4]Mixed model for repeated measures
Comparison: 48 hours; Treatment comparison. The analysis was based on an MMRM with treatment, timepoint, treatment by timepoint interaction, and GA group as fixed effects and pre-procedure SpO2 as a covariate.p-value: 0.08995% CI: [-0.3, 4.3]Mixed model for repeated measures
Comparison: 72 hours; Treatment comparison. The analysis was based on an MMRM with treatment, timepoint, treatment by timepoint interaction, and GA group as fixed effects and pre-procedure SpO2 as a covariate.p-value: 0.11595% CI: [-0.5, 4.4]Mixed model for repeated measures
Comparison: 120 hours; Treatment comparison. The analysis was based on an MMRM with treatment, timepoint, treatment by timepoint interaction, and GA group as fixed effects and pre-procedure SpO2 as a covariate.p-value: 0.28495% CI: [-1, 3.3]Mixed model for repeated measures