Respiratory Distress Syndrome, Newborn
Conditions
Brief summary
Respiratory distress syndrome (RDS), caused by surfactant deficiency, is the leading cause of mortality and morbidity in preterm infants. Intratracheal instillation, the only approved means of surfactant delivery, requires endotracheal intubation and mechanical ventilation with their attendant risks. Interventions that decrease need for intubation and mechanical ventilation like noninvasive ventilation (NIV) including nasal continuous positive airway pressure, high flow nasal cannula or nasal intermittent mandatory ventilation are increasingly being used for initial respiratory support in preterm neonates with RDS to improve outcomes. Aerosolized surfactant delivered during NIV is an innovative and promising concept for the treatment of RDS - retaining the advantages of early surfactant with alveolar recruitment while obviating the risks of intubation and mechanical ventilation. The investigators overall hypothesis is that treatment of RDS with aerosolized surfactant in preterm infants undergoing NIV is safe and feasible and will result in short-term improvement in oxygenation and ventilation. The objective of this proposal is to perform a single-center unblinded Phase II randomized clinical trial of aerosolized surfactant for the treatment of RDS in preterm neonates undergoing NIV. Funding Source - FDA-OOPD.
Interventions
DRUGSurfactant
Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer.
Sponsors
Sood, Beena G., MD, MS
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 24 Hours
Healthy volunteers
No
Inclusion criteria
1. Infants admitted to the NICU at Hutzel Women's Hospital (HWH)/Children's Hospital of Michigan (CHM) 2. Gestational age of 240/7-366/7 weeks 3. Postnatal age ≤ 24 hours 4. Clinical diagnosis of RDS based on (i) presence of at least two of the four classic symptoms (need of supplemental oxygen, tachypnea, intercostal retractions or grunting), and (ii) exclusion of other causes of respiratory failure and (iii) Clinician intent to administer surfactant if infant requires intubation 5. Respiratory support with NIV (CPAP or NIPPV or HFNC) with FiO2 ≥25% or PEEP ≥ 4 cmH20 or HFNC rate ≥ 2 LPM for ≤8 hours 6. Written informed consent from parent/guardian
Exclusion criteria
1. Previous receipt of surfactant 2. Infants with respiratory distress who are unstable and require immediate intubation 3. Active air leak syndrome (e.g. pneumothorax, pneumomediastinum) 4. Lethal congenital malformations; death anticipated within first 3 days of life; decision to withhold support 5. Serious abdominal, cardiac, airway or respiratory malformations including tracheal esophageal fistula, intestinal atresia, omphalocele, gastroschisis, pulmonary hypoplasia, or diaphragmatic hernia 6. Neuromuscular disorder resulting in respiratory compromise
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events as a Measure of Safety and Feasibility | During and within 6 hours after end of study drug administration, expected maximum of approximately 14 hours | Since surfactant reflux is typically considered to be one of the most likely adverse events associated with the intervention, it was planned to report the number of participants specifically with surfactant reflux for this Outcome Measure |
| Patient Status as Evaluated by Dose Level | During study drug administration, expected maximum of approximately 8 hours for adverse effects and infant comfort; need for intubation was assessed within 72 hours of study intervention. | Optimal dosing schedule was determined by preliminary evidence of efficacy (Need for intubation within 72 hours), lack of adverse effects, and overall infant comfort as assessed by bedside clinical caregivers. |
| Short Term Efficacy as Assessed by Need for Intubation | Within 72 hours of study intervention | It will be suggested that infants be intubated and receive MV if they met 2 or more of 5 failure criteria: i). worsening clinical signs of respiratory distress (increasing tachypnea; expiratory grunting; intercostal, subcostal, and/or sternal recession); ii). apnea treated with positive pressure ventilation (PPV) by mask on 2 or more occasions in 1 hour; iii). FIO2 \>0.5 to maintain pulse oxygen saturations 90%-95% for \>30 minutes; iv). pH \<7.2 on 2 arterial or capillary blood gases taken \>30 minutes apart; and v). partial pressure of CO2 (PCO2) of \>65 mm Hg on 2 CBG/ABGs taken 30 minutes apart. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Vital Signs - Heart Rate | 60±30 minutes after end of study intervention | Vital signs included heart rate, respiratory rate and systolic blood pressure |
| Vital Signs - Respiratory Rate | 60±30 minutes after end of study intervention | Vital signs included heart rate, respiratory rate and systolic blood pressure |
| Vital Signs - Systolic Blood Pressure | 60±30 minutes after end of study intervention | Systolic blood pressure |
| Number of Doses of Surfactant - Aerosolized & Intratracheal | Within 72 hours of study intervention | — |
| Pneumothorax, Pneumomediastinum or Other Air Leak | Within 72 hours of study intervention | — |
| Changes in Cerebral Oxygenation From Baseline as Evaluated at End of Study Intervention | During and within 6 hours after end of study intervention, expected maximum of approximately 14 hours | Changes in cerebral oxygenation from baseline as evaluated at end of study intervention |
| Changes in Surfactant Activity in Gastric Aspirates | During study intervention, expected maximum of approximately 8 hours | Concentration of major surfactant lipid (PC 16:0/16:0) |
| Blood Gas Parameters - pH | 60±30 minutes after end of study intervention | Blood gas pH |
| Duration of Supplemental Oxygen, Intensive Care, Hospital Stay | During initial hospital stay, expected <= 120 days | Duration of supplemental oxygen, and hospital stay |
| Age at Start of Feeds, Feeding Progression, Age at Full Enteral Feeds | During initial hospital stay, expected 1st 2 weeks of life | Age at start of feeds, and age at full enteral feeds presented in days |
| Need for Blood Transfusions | During initial hospital stay, expected <= 120 days | Number of infants requiring blood transfusions |
| Growth Parameters | At 7 days, 28 days, 36 weeks corrected GA and discharge | Weight at discharge |
| Morbidities Associated With Prematurity | During initial hospital stay, expected <= 120 days | Grade III & IV IVH PDA requiring ligation ROP treated with Laser Surgical NEC BPD |
| Survival to Hospital Discharge | During initial hospital stay, expected <= 120 days | Survival to hospital discharge |
| Survival to Discharge Without Severe Morbidity | During initial hospital stay, expected <= 120 days | Survival to discharge without severe BPD, severe IVH, surgical NEC or ROP treated with Laser |
| Cumulative Duration of Non-invasive and Invasive Ventilation | at discharge | Cumulative duration of non-invasive and invasive ventilation at discharge |
| Blood Gas Parameters - pCO2 | 60±30 minutes after end of study intervention | Blood gas pCO2. |
| Pulse Oximetry | 60±30 minutes after end of study intervention | Transcutaneous Pulse oximetry |
Countries
United States
Participant flow
Pre-assignment details
Of 159 enrolled and randomized participants, 149 met eligibility criteria and proceeded with treatment.
Participants by arm
| Arm | Count |
|---|---|
| Dose Schedule I Surfactant dose to be administered as aerosol - 100 mg phospholipid/kg.
Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer. | 37 |
| Dose Schedule II Surfactant dose to be administered as aerosol - 200 mg phospholipid/kg.
Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer. | 38 |
| Dose Schedule III Surfactant dose to be administered as aerosol - 100 mg phospholipid/kg.
Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer. | 35 |
| Dose Schedule IV Surfactant dose to be administered as aerosol - 200 mg phospholipid/kg.
Surfactant: Two doses of surfactant to be administered as aerosol will be tested - 100 mg phospholipid/kg and 200 mg phospholipid/kg. Each dose will be tested at two dilutions and with two nebulizers. Each enrolled infant may receive a maximum of two aerosol treatments of a single dilution with a single nebulizer. | 39 |
| Total | 149 |
Baseline characteristics
| Characteristic | Dose Schedule I | Dose Schedule II | Dose Schedule III | Dose Schedule IV | Total |
|---|---|---|---|---|---|
| Age, Continuous | 31.4 weeks STANDARD_DEVIATION 3 | 31.6 weeks STANDARD_DEVIATION 3.3 | 31.0 weeks STANDARD_DEVIATION 3 | 31.7 weeks STANDARD_DEVIATION 3.2 | 31.4 weeks STANDARD_DEVIATION 3.1 |
| Age, Customized GA strata GA strata I (24-28 weeks) | 7 Participants | 7 Participants | 8 Participants | 7 Participants | 29 Participants |
| Age, Customized GA strata GA strata II (29-32 weeks) | 16 Participants | 15 Participants | 14 Participants | 15 Participants | 60 Participants |
| Age, Customized GA strata GA strata III (33-36 weeks) | 14 Participants | 16 Participants | 13 Participants | 17 Participants | 60 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 2 Participants | 1 Participants | 1 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 37 Participants | 35 Participants | 33 Participants | 36 Participants | 141 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants | 2 Participants | 4 Participants |
| Region of Enrollment United States | 37 Participants | 38 Participants | 35 Participants | 39 Participants | 149 Participants |
| Sex: Female, Male Female | 20 Participants | 24 Participants | 20 Participants | 14 Participants | 78 Participants |
| Sex: Female, Male Male | 17 Participants | 14 Participants | 15 Participants | 25 Participants | 71 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 37 | 0 / 38 | 0 / 35 | 0 / 39 |
| other Total, other adverse events | 8 / 37 | 18 / 38 | 12 / 35 | 20 / 39 |
| serious Total, serious adverse events | 0 / 37 | 0 / 38 | 0 / 35 | 0 / 39 |
Outcome results
Primary
Number of Participants With Adverse Events as a Measure of Safety and Feasibility
Since surfactant reflux is typically considered to be one of the most likely adverse events associated with the intervention, it was planned to report the number of participants specifically with surfactant reflux for this Outcome Measure
Time frame: During and within 6 hours after end of study drug administration, expected maximum of approximately 14 hours
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dose Schedule I | Number of Participants With Adverse Events as a Measure of Safety and Feasibility | 3 Participants |
| Dose Schedule II | Number of Participants With Adverse Events as a Measure of Safety and Feasibility | 8 Participants |
| Dose Schedule III | Number of Participants With Adverse Events as a Measure of Safety and Feasibility | 4 Participants |
| Dose Schedule IV | Number of Participants With Adverse Events as a Measure of Safety and Feasibility | 12 Participants |
Primary
Patient Status as Evaluated by Dose Level
Optimal dosing schedule was determined by preliminary evidence of efficacy (Need for intubation within 72 hours), lack of adverse effects, and overall infant comfort as assessed by bedside clinical caregivers.
Time frame: During study drug administration, expected maximum of approximately 8 hours for adverse effects and infant comfort; need for intubation was assessed within 72 hours of study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose Schedule I | Patient Status as Evaluated by Dose Level | Need for Intubation within 72 hours | 3 Participants |
| Dose Schedule I | Patient Status as Evaluated by Dose Level | Overall infant comfort during AS as assessed by bedside nurse (infant most comfortable) | 30 Participants |
| Dose Schedule I | Patient Status as Evaluated by Dose Level | Adverse events - surfactant reflux | 3 Participants |
| Dose Schedule II | Patient Status as Evaluated by Dose Level | Need for Intubation within 72 hours | 3 Participants |
| Dose Schedule II | Patient Status as Evaluated by Dose Level | Overall infant comfort during AS as assessed by bedside nurse (infant most comfortable) | 27 Participants |
| Dose Schedule II | Patient Status as Evaluated by Dose Level | Adverse events - surfactant reflux | 8 Participants |
| Dose Schedule III | Patient Status as Evaluated by Dose Level | Adverse events - surfactant reflux | 4 Participants |
| Dose Schedule III | Patient Status as Evaluated by Dose Level | Need for Intubation within 72 hours | 5 Participants |
| Dose Schedule III | Patient Status as Evaluated by Dose Level | Overall infant comfort during AS as assessed by bedside nurse (infant most comfortable) | 26 Participants |
| Dose Schedule IV | Patient Status as Evaluated by Dose Level | Need for Intubation within 72 hours | 4 Participants |
| Dose Schedule IV | Patient Status as Evaluated by Dose Level | Overall infant comfort during AS as assessed by bedside nurse (infant most comfortable) | 26 Participants |
| Dose Schedule IV | Patient Status as Evaluated by Dose Level | Adverse events - surfactant reflux | 12 Participants |
Primary
Short Term Efficacy as Assessed by Need for Intubation
It will be suggested that infants be intubated and receive MV if they met 2 or more of 5 failure criteria: i). worsening clinical signs of respiratory distress (increasing tachypnea; expiratory grunting; intercostal, subcostal, and/or sternal recession); ii). apnea treated with positive pressure ventilation (PPV) by mask on 2 or more occasions in 1 hour; iii). FIO2 \>0.5 to maintain pulse oxygen saturations 90%-95% for \>30 minutes; iv). pH \<7.2 on 2 arterial or capillary blood gases taken \>30 minutes apart; and v). partial pressure of CO2 (PCO2) of \>65 mm Hg on 2 CBG/ABGs taken 30 minutes apart.
Time frame: Within 72 hours of study intervention
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dose Schedule I | Short Term Efficacy as Assessed by Need for Intubation | 3 Participants |
| Dose Schedule II | Short Term Efficacy as Assessed by Need for Intubation | 3 Participants |
| Dose Schedule III | Short Term Efficacy as Assessed by Need for Intubation | 5 Participants |
| Dose Schedule IV | Short Term Efficacy as Assessed by Need for Intubation | 4 Participants |
p-value: 0.399t-test, 2 sided
Secondary
Age at Start of Feeds, Feeding Progression, Age at Full Enteral Feeds
Age at start of feeds, and age at full enteral feeds presented in days
Time frame: During initial hospital stay, expected 1st 2 weeks of life
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Schedule I | Age at Start of Feeds, Feeding Progression, Age at Full Enteral Feeds | Age at start of feeds (days) | 1.3 age in days | Standard Deviation 0.7 |
| Dose Schedule I | Age at Start of Feeds, Feeding Progression, Age at Full Enteral Feeds | Age at full enteral feeds (days) | 11.2 age in days | Standard Deviation 8.8 |
| Dose Schedule II | Age at Start of Feeds, Feeding Progression, Age at Full Enteral Feeds | Age at full enteral feeds (days) | 7.8 age in days | Standard Deviation 7.3 |
| Dose Schedule II | Age at Start of Feeds, Feeding Progression, Age at Full Enteral Feeds | Age at start of feeds (days) | 1.6 age in days | Standard Deviation 1.7 |
| Dose Schedule III | Age at Start of Feeds, Feeding Progression, Age at Full Enteral Feeds | Age at start of feeds (days) | 1.8 age in days | Standard Deviation 1.7 |
| Dose Schedule III | Age at Start of Feeds, Feeding Progression, Age at Full Enteral Feeds | Age at full enteral feeds (days) | 11.8 age in days | Standard Deviation 11.7 |
| Dose Schedule IV | Age at Start of Feeds, Feeding Progression, Age at Full Enteral Feeds | Age at start of feeds (days) | 1.5 age in days | Standard Deviation 1.1 |
| Dose Schedule IV | Age at Start of Feeds, Feeding Progression, Age at Full Enteral Feeds | Age at full enteral feeds (days) | 12.9 age in days | Standard Deviation 12.9 |
Secondary
Blood Gas Parameters - pCO2
Blood gas pCO2.
Time frame: 60±30 minutes after end of study intervention
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dose Schedule I | Blood Gas Parameters - pCO2 | 45 mmHg | Standard Deviation 8 |
| Dose Schedule II | Blood Gas Parameters - pCO2 | 45 mmHg | Standard Deviation 9 |
| Dose Schedule III | Blood Gas Parameters - pCO2 | 43 mmHg | Standard Deviation 6 |
| Dose Schedule IV | Blood Gas Parameters - pCO2 | 45 mmHg | Standard Deviation 7 |
Secondary
Blood Gas Parameters - pH
Blood gas pH
Time frame: 60±30 minutes after end of study intervention
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dose Schedule I | Blood Gas Parameters - pH | 7.35 pH units for pH, mmHg for pCO2 | Standard Deviation 0.05 |
| Dose Schedule II | Blood Gas Parameters - pH | 7.36 pH units for pH, mmHg for pCO2 | Standard Deviation 0.07 |
| Dose Schedule III | Blood Gas Parameters - pH | 7.36 pH units for pH, mmHg for pCO2 | Standard Deviation 0.06 |
| Dose Schedule IV | Blood Gas Parameters - pH | 7.35 pH units for pH, mmHg for pCO2 | Standard Deviation 0.05 |
Secondary
Changes in Cerebral Oxygenation From Baseline as Evaluated at End of Study Intervention
Changes in cerebral oxygenation from baseline as evaluated at end of study intervention
Time frame: During and within 6 hours after end of study intervention, expected maximum of approximately 14 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dose Schedule I | Changes in Cerebral Oxygenation From Baseline as Evaluated at End of Study Intervention | 79 percentage of oxygen saturation | Standard Deviation 8 |
| Dose Schedule II | Changes in Cerebral Oxygenation From Baseline as Evaluated at End of Study Intervention | 80 percentage of oxygen saturation | Standard Deviation 8 |
| Dose Schedule III | Changes in Cerebral Oxygenation From Baseline as Evaluated at End of Study Intervention | 78 percentage of oxygen saturation | Standard Deviation 11 |
| Dose Schedule IV | Changes in Cerebral Oxygenation From Baseline as Evaluated at End of Study Intervention | 79 percentage of oxygen saturation | Standard Deviation 8 |
Secondary
Changes in Surfactant Activity in Gastric Aspirates
Concentration of major surfactant lipid (PC 16:0/16:0)
Time frame: During study intervention, expected maximum of approximately 8 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dose Schedule I | Changes in Surfactant Activity in Gastric Aspirates | 10.9 ng per mg of protein | Standard Deviation 14.6 |
| Dose Schedule II | Changes in Surfactant Activity in Gastric Aspirates | 9.5 ng per mg of protein | Standard Deviation 9.2 |
| Dose Schedule III | Changes in Surfactant Activity in Gastric Aspirates | 8.8 ng per mg of protein | Standard Deviation 7.8 |
| Dose Schedule IV | Changes in Surfactant Activity in Gastric Aspirates | 8.0 ng per mg of protein | Standard Deviation 8 |
Secondary
Cumulative Duration of Non-invasive and Invasive Ventilation
Cumulative duration of non-invasive and invasive ventilation at discharge
Time frame: at discharge
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Schedule I | Cumulative Duration of Non-invasive and Invasive Ventilation | Duration of NIV (days) | 4.5 number of days | Standard Deviation 8.1 |
| Dose Schedule I | Cumulative Duration of Non-invasive and Invasive Ventilation | Duration of Invasive ventilation (days) | 1.3 number of days | Standard Deviation 5.1 |
| Dose Schedule II | Cumulative Duration of Non-invasive and Invasive Ventilation | Duration of Invasive ventilation (days) | 0.9 number of days | Standard Deviation 4 |
| Dose Schedule II | Cumulative Duration of Non-invasive and Invasive Ventilation | Duration of NIV (days) | 7.0 number of days | Standard Deviation 14.6 |
| Dose Schedule III | Cumulative Duration of Non-invasive and Invasive Ventilation | Duration of NIV (days) | 7.9 number of days | Standard Deviation 14.2 |
| Dose Schedule III | Cumulative Duration of Non-invasive and Invasive Ventilation | Duration of Invasive ventilation (days) | 1.6 number of days | Standard Deviation 5.1 |
| Dose Schedule IV | Cumulative Duration of Non-invasive and Invasive Ventilation | Duration of NIV (days) | 6.1 number of days | Standard Deviation 14.7 |
| Dose Schedule IV | Cumulative Duration of Non-invasive and Invasive Ventilation | Duration of Invasive ventilation (days) | 2.2 number of days | Standard Deviation 7.4 |
Secondary
Duration of Supplemental Oxygen, Intensive Care, Hospital Stay
Duration of supplemental oxygen, and hospital stay
Time frame: During initial hospital stay, expected <= 120 days
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Schedule I | Duration of Supplemental Oxygen, Intensive Care, Hospital Stay | Duration of supplemental oxygen (days) | 7.4 number of days | Standard Deviation 18.5 |
| Dose Schedule I | Duration of Supplemental Oxygen, Intensive Care, Hospital Stay | Length of hospital stay (days) | 29.9 number of days | Standard Deviation 28 |
| Dose Schedule II | Duration of Supplemental Oxygen, Intensive Care, Hospital Stay | Length of hospital stay (days) | 26.4 number of days | Standard Deviation 24.3 |
| Dose Schedule II | Duration of Supplemental Oxygen, Intensive Care, Hospital Stay | Duration of supplemental oxygen (days) | 9.0 number of days | Standard Deviation 22.9 |
| Dose Schedule III | Duration of Supplemental Oxygen, Intensive Care, Hospital Stay | Duration of supplemental oxygen (days) | 10.7 number of days | Standard Deviation 25.2 |
| Dose Schedule III | Duration of Supplemental Oxygen, Intensive Care, Hospital Stay | Length of hospital stay (days) | 32.1 number of days | Standard Deviation 29.9 |
| Dose Schedule IV | Duration of Supplemental Oxygen, Intensive Care, Hospital Stay | Duration of supplemental oxygen (days) | 8.9 number of days | Standard Deviation 29.3 |
| Dose Schedule IV | Duration of Supplemental Oxygen, Intensive Care, Hospital Stay | Length of hospital stay (days) | 28.3 number of days | Standard Deviation 30.8 |
Secondary
Growth Parameters
Weight at discharge
Time frame: At 7 days, 28 days, 36 weeks corrected GA and discharge
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dose Schedule I | Growth Parameters | 2153 grams | Standard Deviation 458 |
| Dose Schedule II | Growth Parameters | 2222 grams | Standard Deviation 431 |
| Dose Schedule III | Growth Parameters | 2235 grams | Standard Deviation 561 |
| Dose Schedule IV | Growth Parameters | 2281 grams | Standard Deviation 522 |
Secondary
Morbidities Associated With Prematurity
Grade III & IV IVH PDA requiring ligation ROP treated with Laser Surgical NEC BPD
Time frame: During initial hospital stay, expected <= 120 days
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose Schedule I | Morbidities Associated With Prematurity | Surgical NEC | 0 Participants |
| Dose Schedule I | Morbidities Associated With Prematurity | PDA requiring ligation | 0 Participants |
| Dose Schedule I | Morbidities Associated With Prematurity | BPD | 4 Participants |
| Dose Schedule I | Morbidities Associated With Prematurity | ROP treated with Laser | 0 Participants |
| Dose Schedule I | Morbidities Associated With Prematurity | Grade III & IV IVH | 0 Participants |
| Dose Schedule II | Morbidities Associated With Prematurity | ROP treated with Laser | 1 Participants |
| Dose Schedule II | Morbidities Associated With Prematurity | Surgical NEC | 0 Participants |
| Dose Schedule II | Morbidities Associated With Prematurity | BPD | 4 Participants |
| Dose Schedule II | Morbidities Associated With Prematurity | PDA requiring ligation | 1 Participants |
| Dose Schedule II | Morbidities Associated With Prematurity | Grade III & IV IVH | 1 Participants |
| Dose Schedule III | Morbidities Associated With Prematurity | ROP treated with Laser | 0 Participants |
| Dose Schedule III | Morbidities Associated With Prematurity | Grade III & IV IVH | 0 Participants |
| Dose Schedule III | Morbidities Associated With Prematurity | PDA requiring ligation | 0 Participants |
| Dose Schedule III | Morbidities Associated With Prematurity | Surgical NEC | 2 Participants |
| Dose Schedule III | Morbidities Associated With Prematurity | BPD | 5 Participants |
| Dose Schedule IV | Morbidities Associated With Prematurity | Surgical NEC | 2 Participants |
| Dose Schedule IV | Morbidities Associated With Prematurity | PDA requiring ligation | 0 Participants |
| Dose Schedule IV | Morbidities Associated With Prematurity | Grade III & IV IVH | 1 Participants |
| Dose Schedule IV | Morbidities Associated With Prematurity | ROP treated with Laser | 1 Participants |
| Dose Schedule IV | Morbidities Associated With Prematurity | BPD | 2 Participants |
Secondary
Need for Blood Transfusions
Number of infants requiring blood transfusions
Time frame: During initial hospital stay, expected <= 120 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dose Schedule I | Need for Blood Transfusions | 10 Participants |
| Dose Schedule II | Need for Blood Transfusions | 6 Participants |
| Dose Schedule III | Need for Blood Transfusions | 8 Participants |
| Dose Schedule IV | Need for Blood Transfusions | 7 Participants |
Secondary
Number of Doses of Surfactant - Aerosolized & Intratracheal
Time frame: Within 72 hours of study intervention
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose Schedule I | Number of Doses of Surfactant - Aerosolized & Intratracheal | One dose of aerosolized surfactant | 10 Participants |
| Dose Schedule I | Number of Doses of Surfactant - Aerosolized & Intratracheal | Two doses of aerosolized surfactant | 27 Participants |
| Dose Schedule I | Number of Doses of Surfactant - Aerosolized & Intratracheal | No. of doses of intratracheal surfactant - one | 0 Participants |
| Dose Schedule I | Number of Doses of Surfactant - Aerosolized & Intratracheal | No. of doses of intratracheal surfactant - two | 2 Participants |
| Dose Schedule I | Number of Doses of Surfactant - Aerosolized & Intratracheal | No. of doses of intratracheal surfactant - three | 0 Participants |
| Dose Schedule I | Number of Doses of Surfactant - Aerosolized & Intratracheal | No. of doses of intratracheal surfactant - four | 0 Participants |
| Dose Schedule II | Number of Doses of Surfactant - Aerosolized & Intratracheal | No. of doses of intratracheal surfactant - four | 1 Participants |
| Dose Schedule II | Number of Doses of Surfactant - Aerosolized & Intratracheal | No. of doses of intratracheal surfactant - two | 0 Participants |
| Dose Schedule II | Number of Doses of Surfactant - Aerosolized & Intratracheal | One dose of aerosolized surfactant | 14 Participants |
| Dose Schedule II | Number of Doses of Surfactant - Aerosolized & Intratracheal | No. of doses of intratracheal surfactant - one | 2 Participants |
| Dose Schedule II | Number of Doses of Surfactant - Aerosolized & Intratracheal | Two doses of aerosolized surfactant | 24 Participants |
| Dose Schedule II | Number of Doses of Surfactant - Aerosolized & Intratracheal | No. of doses of intratracheal surfactant - three | 0 Participants |
| Dose Schedule III | Number of Doses of Surfactant - Aerosolized & Intratracheal | Two doses of aerosolized surfactant | 22 Participants |
| Dose Schedule III | Number of Doses of Surfactant - Aerosolized & Intratracheal | No. of doses of intratracheal surfactant - one | 2 Participants |
| Dose Schedule III | Number of Doses of Surfactant - Aerosolized & Intratracheal | No. of doses of intratracheal surfactant - two | 1 Participants |
| Dose Schedule III | Number of Doses of Surfactant - Aerosolized & Intratracheal | No. of doses of intratracheal surfactant - four | 0 Participants |
| Dose Schedule III | Number of Doses of Surfactant - Aerosolized & Intratracheal | No. of doses of intratracheal surfactant - three | 1 Participants |
| Dose Schedule III | Number of Doses of Surfactant - Aerosolized & Intratracheal | One dose of aerosolized surfactant | 13 Participants |
| Dose Schedule IV | Number of Doses of Surfactant - Aerosolized & Intratracheal | No. of doses of intratracheal surfactant - three | 2 Participants |
| Dose Schedule IV | Number of Doses of Surfactant - Aerosolized & Intratracheal | No. of doses of intratracheal surfactant - four | 0 Participants |
| Dose Schedule IV | Number of Doses of Surfactant - Aerosolized & Intratracheal | Two doses of aerosolized surfactant | 25 Participants |
| Dose Schedule IV | Number of Doses of Surfactant - Aerosolized & Intratracheal | No. of doses of intratracheal surfactant - two | 1 Participants |
| Dose Schedule IV | Number of Doses of Surfactant - Aerosolized & Intratracheal | One dose of aerosolized surfactant | 14 Participants |
| Dose Schedule IV | Number of Doses of Surfactant - Aerosolized & Intratracheal | No. of doses of intratracheal surfactant - one | 0 Participants |
Secondary
Pneumothorax, Pneumomediastinum or Other Air Leak
Time frame: Within 72 hours of study intervention
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dose Schedule I | Pneumothorax, Pneumomediastinum or Other Air Leak | 0 Participants |
| Dose Schedule II | Pneumothorax, Pneumomediastinum or Other Air Leak | 1 Participants |
| Dose Schedule III | Pneumothorax, Pneumomediastinum or Other Air Leak | 0 Participants |
| Dose Schedule IV | Pneumothorax, Pneumomediastinum or Other Air Leak | 1 Participants |
Secondary
Pulse Oximetry
Transcutaneous Pulse oximetry
Time frame: 60±30 minutes after end of study intervention
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dose Schedule I | Pulse Oximetry | 95.95 percentage of oxygen saturation | Standard Deviation 3.34 |
| Dose Schedule II | Pulse Oximetry | 96.95 percentage of oxygen saturation | Standard Deviation 5.22 |
| Dose Schedule III | Pulse Oximetry | 97.37 percentage of oxygen saturation | Standard Deviation 3.16 |
| Dose Schedule IV | Pulse Oximetry | 97.47 percentage of oxygen saturation | Standard Deviation 3.07 |
Secondary
Survival to Discharge Without Severe Morbidity
Survival to discharge without severe BPD, severe IVH, surgical NEC or ROP treated with Laser
Time frame: During initial hospital stay, expected <= 120 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dose Schedule I | Survival to Discharge Without Severe Morbidity | 37 Participants |
| Dose Schedule II | Survival to Discharge Without Severe Morbidity | 35 Participants |
| Dose Schedule III | Survival to Discharge Without Severe Morbidity | 33 Participants |
| Dose Schedule IV | Survival to Discharge Without Severe Morbidity | 35 Participants |
Secondary
Survival to Hospital Discharge
Survival to hospital discharge
Time frame: During initial hospital stay, expected <= 120 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dose Schedule I | Survival to Hospital Discharge | 37 Participants |
| Dose Schedule II | Survival to Hospital Discharge | 38 Participants |
| Dose Schedule III | Survival to Hospital Discharge | 35 Participants |
| Dose Schedule IV | Survival to Hospital Discharge | 39 Participants |
Secondary
Vital Signs - Heart Rate
Vital signs included heart rate, respiratory rate and systolic blood pressure
Time frame: 60±30 minutes after end of study intervention
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dose Schedule I | Vital Signs - Heart Rate | 134 beats/minute | Standard Deviation 12 |
| Dose Schedule II | Vital Signs - Heart Rate | 142 beats/minute | Standard Deviation 14 |
| Dose Schedule III | Vital Signs - Heart Rate | 138 beats/minute | Standard Deviation 12 |
| Dose Schedule IV | Vital Signs - Heart Rate | 136 beats/minute | Standard Deviation 12 |
Secondary
Vital Signs - Respiratory Rate
Vital signs included heart rate, respiratory rate and systolic blood pressure
Time frame: 60±30 minutes after end of study intervention
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dose Schedule I | Vital Signs - Respiratory Rate | 47 breaths/minute | Standard Deviation 17 |
| Dose Schedule II | Vital Signs - Respiratory Rate | 47 breaths/minute | Standard Deviation 15 |
| Dose Schedule III | Vital Signs - Respiratory Rate | 46 breaths/minute | Standard Deviation 15 |
| Dose Schedule IV | Vital Signs - Respiratory Rate | 47 breaths/minute | Standard Deviation 15 |
Secondary
Vital Signs - Systolic Blood Pressure
Systolic blood pressure
Time frame: 60±30 minutes after end of study intervention
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dose Schedule I | Vital Signs - Systolic Blood Pressure | 54 mmHg | Standard Deviation 9 |
| Dose Schedule II | Vital Signs - Systolic Blood Pressure | 51 mmHg | Standard Deviation 8 |
| Dose Schedule III | Vital Signs - Systolic Blood Pressure | 54 mmHg | Standard Deviation 10 |
| Dose Schedule IV | Vital Signs - Systolic Blood Pressure | 53 mmHg | Standard Deviation 9 |