Respiratory Distress Syndrome, Newborn
Conditions
Keywords
intubation, surfactant, continuous positive airway pressure, aerosol, respiratory distress syndrome
Brief summary
This study is to evaluate the safety and efficacy of lucinactant for inhalation in conjunction with nCPAP, in comparison to nCPAP alone, in preterm neonates with RDS, as assessed by the incidence of and time to respiratory failure and/or death due to RDS in the first 72 hours and 28 days of life. Half of the subjects will receive lucinactant for inhalation and half will receive standard of care (nCPAP alone).
Detailed description
An unmet medical need exists for a means to deliver surfactant replacement therapy (SRT) to preterm neonates with RDS supported with nCPAP early in the course of the disease. This strategy has the potential to improve RDS prior to the development of respiratory failure, thereby avoiding the need for endotracheal intubation and mechanical ventilation (MV), or reduce the duration of MV, and the resultant potential for morbidity and complications. The ability to administer SRT via aerosol has the potential to address this unmet need. Lucinactant for inhalation (AEROSURF) is an investigational drug-device combination product, designed to deliver aerosolized SRT to preterm neonates with RDS who are being supported with nCPAP. The drug component of lucinactant for inhalation is lyophilized lucinactant, a lyophilized form of SURFAXIN® (lucinactant) Intratracheal Suspension. The device component, the AEROSURF Delivery System (ADS), the next-generation device following use of the prototype device in earlier trials, uses novel technology to aerosolize lucinactant for inhalation. This study evaluates the safety and efficacy of lucinactant for inhalation in conjunction with nCPAP, in comparison to nCPAP alone, in preterm neonates with RDS, as assessed by pre-specified outcome measures. In addition, this study will evaluate the device and the ability to administer up to 3 repeat doses.
Interventions
COMBINATION_PRODUCTLucinactant for Inhalation
A drug-device combination product that delivers aerosolized SRT to preterm neonates with RDS who are being supported with nasal continuous positive airway pressure (nCPAP).
OTHERnCPAP Only
Nasal continuous positive airway pressure (nCPAP) alone
Sponsors
Windtree Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
The first 2 subjects at each site for each cohort will be dosed with open-label active treatment for training purposes. Following the first 2 subjects, preparation and delivery of treatment will be blinded from the study staff. Treatment will be delivered behind a partition and no information about treatment will be given to investigator, parents, or other applicable study staff.
Intervention model description
This study is a multinational, multicenter, double-blind (masked), parallel group, randomized, controlled study, in preterm neonates 26 to 32 completed weeks post-menstrual age (PMA).
Eligibility
Sex/Gender
ALL
Age
30 Minutes to 6 Hours
Healthy volunteers
No
Inclusion criteria
* Signed ICF from legally authorized representative. * Gestational age: 26 to 32+6 weeks PMA. * Successful implementation of non-invasive support or ventilation within 30 minutes after birth. * Spontaneous breathing. * Investigator determination of RDS. A chest x-ray should be obtained before treatment to confirm the diagnosis. * Within the first 6 hours after birth, requires an nCPAP of 5 to 7 cm H2O that is clinically indicated for at least 15 minutes with an FiO2 \> 0.25 to ≤ 0.35 to maintain SpO2 of 90% to 95%.
Exclusion criteria
* A heart rate that cannot be stabilized above 100 bpm within 5 minutes of birth. * Recurrent episodes of apnea requiring positive pressure ventilation. * A 5 minute Apgar score \< 5. * Major congenital malformation(s) or craniofacial abnormalities that preclude the use of nCPAP. * Clinically significant diseases or conditions other than RDS which could potentially interfere with cardiopulmonary function. * A known or suspected chromosomal abnormality or syndrome. * Premature rupture of membranes \> 3 weeks. * Hemodynamic instability requiring vasopressors or steroids for hemodynamic support and/or presumed clinical sepsis. * A need for intubation and/or invasive mechanical ventilation at any time before enrollment into the study. * The administration (or plan for administration) of another investigational agent or investigational medical device, any other surfactant agent, or systemic corticosteroids. * Presence of air leak on the baseline chest radiograph or diagnosed via ultrasound or illumination.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Respiratory Failure or Death | 28 days of life | Number of participants with respiratory failure due to RDS or death. Respiratory failure due to RDS is defined as intubation for mechanical ventilation and/or surfactant administration |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number With BPD | 36 weeks post-menstrual age (PMA) | Number of participants with bronchopulmonary dysplasia (BPD) |
| Mortality | 36 weeks PMA or 28 days of life (whichever is later) | All-cause mortality |
| Number of Participants With Common Complications of Prematurity | 36 weeks PMA | Number of participants with complications including intraventricular hemorrhage, periventricular leukomalacia, pulmonary hemorrhage, apnea, necrotizing enterocolitis, patent ductus arteriosus, acquired sepsis, and retinopathy of prematurity. |
Countries
Poland
Participant flow
Recruitment details
Enrollment period: 18 April 2020 to 19 January 2021 Enrollment occurred in neonatal intensive care units.
Pre-assignment details
Subjects were screened before enrollment. Screen fail reasons included: unable to maintain required FiO2 (majority of screen fails), no determination of RDS, need for mechanical ventilation, outside of enrollment window
Participants by arm
| Arm | Count |
|---|---|
| Lucinactant (160 mg/kg) + nCPAP Lucinactant for inhalation, 160 mg total phospholipids (TPL)/kg Delivered as an aerosol, with up to 3 repeats of 80 mg/kg allowed within 36 hours of birth
Lucinactant for Inhalation: A drug-device combination product that delivers aerosolized SRT to preterm neonates with RDS who are being supported with nCPAP. | 11 |
| nCPAP Only nCPAP Only as sham comparator. Bubble nCPAP is standard of care. Treatment time behind barrier to match active treatment delivery time
nCPAP Only: Nasal CPAP Alone | 1 |
| Total | 12 |
Baseline characteristics
| Characteristic | nCPAP Only | Lucinactant (160 mg/kg) + nCPAP | Total |
|---|---|---|---|
| Age, Continuous | 1.05 hours | 3.25 hours | 3.02 hours |
| Age, Customized Gestational Age | 31.0 weeks | 30.3 weeks | 30.4 weeks |
| Apgar Score at Five Minutes | 8.0 Scores on a scale | 8.0 Scores on a scale | 8.0 Scores on a scale |
| Apgar Score at One Minute | 7.0 Scores on a scale | 7.0 Scores on a scale | 7.0 Scores on a scale |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 11 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 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 | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 11 Participants | 12 Participants |
| Region of Enrollment Poland | 1 participants | 11 participants | 12 participants |
| Sex: Female, Male Female | 1 Participants | 4 Participants | 5 Participants |
| Sex: Female, Male Male | 0 Participants | 7 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 1 |
| other Total, other adverse events | 11 / 11 | 1 / 1 |
| serious Total, serious adverse events | 2 / 11 | 0 / 1 |
Outcome results
Primary
Number of Participants With Respiratory Failure or Death
Number of participants with respiratory failure due to RDS or death. Respiratory failure due to RDS is defined as intubation for mechanical ventilation and/or surfactant administration
Time frame: 28 days of life
Population: Intent-to-Treat
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lucinactant (160 mg/kg) + nCPAP | Number of Participants With Respiratory Failure or Death | 6 Participants |
| nCPAP Only | Number of Participants With Respiratory Failure or Death | 0 Participants |
Secondary
Mortality
All-cause mortality
Time frame: 36 weeks PMA or 28 days of life (whichever is later)
Population: Intent-to-Treat
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lucinactant (160 mg/kg) + nCPAP | Mortality | 0 Participants |
| nCPAP Only | Mortality | 0 Participants |
Secondary
Number of Participants With Common Complications of Prematurity
Number of participants with complications including intraventricular hemorrhage, periventricular leukomalacia, pulmonary hemorrhage, apnea, necrotizing enterocolitis, patent ductus arteriosus, acquired sepsis, and retinopathy of prematurity.
Time frame: 36 weeks PMA
Population: Intent-to-Treat
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lucinactant (160 mg/kg) + nCPAP | Number of Participants With Common Complications of Prematurity | 9 Participants |
| nCPAP Only | Number of Participants With Common Complications of Prematurity | 1 Participants |
Secondary
Number With BPD
Number of participants with bronchopulmonary dysplasia (BPD)
Time frame: 36 weeks post-menstrual age (PMA)
Population: Intent-to-Treat
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lucinactant (160 mg/kg) + nCPAP | Number With BPD | 0 Participants |
| nCPAP Only | Number With BPD | 0 Participants |