Bronchopulmonary Dysplasia, Respiratory Distress Syndrome of Prematurity (Surfactant Dysfunction)
Conditions
Keywords
nitric oxide, surfactant, bronchopulmonary dysplasia, prematurity, neonates, iNO, Infasurf, lung function, ventilated infants
Brief summary
The purpose of this study is to determine if the combination of late doses of Infasurf with inhaled nitric oxide will interact to improve the surfactant function and thus the respiratory status and outcome of treated infants.
Detailed description
Surfactant dysfunction may contribute to the development of bronchopulmonary dysplasia (BPD) in persistently ventilated preterm infants. The investigators conducted a multi-center, randomized, blinded pilot study to assess the safety and efficacy of late administration of surfactant (Calfactant - high in protein B) in combination with prolonged inhaled nitric oxide in preterm infants \< 1000 grams birthweight (BW). Calfactant is one of several types of exogenous surfactant. Calfactant has the highest % of surfactant protein B of the different types.
Interventions
DRUGInfasurf (ONY Inc.)
Infasurf 3ml/kg will be given to infants on study days 0, 3, 7, 10, and 14, if remains intubated.
DRUGSham
Sham instillation (no treatment) will be given to study infants on days 0, 3, 7, 10, and 14, if remains intubated.
Sponsors
Mallinckrodt
ONY
Roberta Ballard
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
7 Days to 14 Days
Healthy volunteers
No
Inclusion criteria
* Less than or equal to 1000 gm. birth weight * Less than or equal to 30 weeks gestational age * Day 7-14 of life * Intubated and mechanically ventilated at any time days 7-14 of life
Exclusion criteria
* Serious congenital malformations * Life expectancy less than 7 days from enrollment * Previous treatment with iNO * Active pulmonary hemorrhage at time of enrollment * Active air leak syndrome at time of enrollment * Bilateral grade IV intracranial hemorrhage prior to enrollment * Less than 48 hours from last clinical dose of early surfactant.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| SP-B Content | One day after dose | SP-B Content is the surfactant protein B found in terms of percentage of phospholipid measured one day after surfactant or sham dose. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Alive Without BPD at 36 Weeks Post Menstrual Age | 36 Weeks Post Menstrual Age | Alive without need for oxygen at 36 weeks post menstrual age. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment Surfactant (Infasurf) ONY, NY Patients receive inhaled nitric oxide and scheduled doses of Infasurf on study days 0, 3, 7, 10, and 14, if infant remains ventilated.
Infasurf (ONY Inc.): Infasurf 3ml/kg will be given to infants on study days 0, 3, 7, 10, and 14. | 43 |
| Sham (no Treatment) Infants receiving inhaled nitric oxide will receive Sham (no treatment) on study days 0, 3, 7, 10, and 14, if infant remains ventilated.
Sham Infants will not receive additional doses of Infasurf. | 42 |
| Total | 85 |
Baseline characteristics
| Characteristic | Treatment Surfactant (Infasurf) ONY, NY | Sham (no Treatment) | Total |
|---|---|---|---|
| Age, Continuous | 9.9 Days STANDARD_DEVIATION 2.2 | 10.5 Days STANDARD_DEVIATION 2.8 | 10.2 Days STANDARD_DEVIATION 2.5 |
| Antenatal Corticosteroids | 32 infants | 33 infants | 65 infants |
| Multiple gestation | 8 infants | 10 infants | 18 infants |
| Prior surfactant treatment | 43 infants | 41 infants | 84 infants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 infants | 0 infants | 0 infants |
| Race/Ethnicity, Customized Asian | 0 infants | 0 infants | 0 infants |
| Race/Ethnicity, Customized Black or African American | 9 infants | 16 infants | 25 infants |
| Race/Ethnicity, Customized Hispanic or Latino | 13 infants | 8 infants | 21 infants |
| Race/Ethnicity, Customized More than one race | 0 infants | 0 infants | 0 infants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 infants | 0 infants | 0 infants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 25 infants | 32 infants | 57 infants |
| Race/Ethnicity, Customized Unknown or Not Reported | 5 infants | 2 infants | 7 infants |
| Race/Ethnicity, Customized White | 29 infants | 24 infants | 53 infants |
| Region of Enrollment United States | 43 infants | 42 infants | 85 infants |
| RSS at entry | 3.4 cm H2O STANDARD_DEVIATION 1.7 | 3.2 cm H2O STANDARD_DEVIATION 1.7 | 3.3 cm H2O STANDARD_DEVIATION 1.7 |
| Sex/Gender, Customized Female | 14 infants | 23 infants | 37 infants |
| Sex/Gender, Customized Male | 29 infants | 19 infants | 48 infants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 43 | 0 / 42 |
| serious Total, serious adverse events | 0 / 43 | 0 / 42 |
Outcome results
Primary
SP-B Content
SP-B Content is the surfactant protein B found in terms of percentage of phospholipid measured one day after surfactant or sham dose.
Time frame: One day after dose
Population: 24 of 43 in the Treatment Group and 18 of 42 in the Sham group had samples analyzed. SpB content recorded as a percentage of Total Phospholipids.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Treatment Surfactant (Infasurf) ONY, NY | SP-B Content | 19.9 Total surfactant protein (% of PL) |
| Sham (no Treatment) | SP-B Content | 13.3 Total surfactant protein (% of PL) |
Secondary
Alive Without BPD at 36 Weeks Post Menstrual Age
Alive without need for oxygen at 36 weeks post menstrual age.
Time frame: 36 Weeks Post Menstrual Age
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment Surfactant (Infasurf) ONY, NY | Alive Without BPD at 36 Weeks Post Menstrual Age | 16 Number of infants |
| Sham (no Treatment) | Alive Without BPD at 36 Weeks Post Menstrual Age | 14 Number of infants |