Meconium Aspiration
Conditions
Keywords
cardiovascular and respiratory diseases, meconium aspiration syndrome, rare disease
Brief summary
OBJECTIVES: Evaluate the safety and efficacy of lucinactant administered by bronchoalveolar lavage (BAL) in the treatment of meconium aspiration syndrome (MAS) in newborn infants.
Detailed description
PROTOCOL OUTLINE: This is a randomized, multicenter study. Patients are randomized to one of two treatment arms. Arm I: Patients receive lucinactant by bronchoalveolar lavage, into the right and left lung, followed by lung drainage. Treatment repeats when patient stabilizes or every 15 minutes for 2 courses. Arm II: Patients receive standard treatment including oxygen, conventional mechanical ventilation, sedation, paralysis, vasopressors, and alkalinization. Patients are followed for 12 months.
Interventions
DRUGLucinactant
Lucinactant suspension was administered as 10 mg total phospholipid (TPL)/mL, by bronchoalveolar lavage within 90 minutes of randomization. The dose was determined based on the infant's body weight such that the total dose was 16 mL/kg for each of the 2 lavage procedures and 32 mL/kg overall. Infants received 2 doses of lucinactant. Each dose consisted of separate lavage procedures for each lung within 15 minutes (up to 60 minutes) of each other.
OTHERStandard Care
The Standard Care (SC) group received therapies including, but not limited to, the use of oxygen, controlled mechanical ventilation (CMV), sedation, paralysis, vasopressors, and/or alkalinization. The use of adjunctive therapies (namely: high frequency oscillatory ventilation, high frequency jet ventilation, bolus surfactant, inhaled nitric oxide, extra-corporeal membrane oxygenation, or systemic corticosteroids) were not included in SC
Sponsors
Windtree Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 48 Hours
Healthy volunteers
No
Inclusion criteria
* Diagnosis of meconium aspiration syndrome (MAS) * Continuous mechanical ventilation (CMV) at time of entry * Enrollment within 48 hours of birth * Gestational age of ≥ 37 weeks * Oxygenation index of ≥ 5 and ≤ 30 * Written informed consent signed and dated by the infant's parent(s) or legal guardian(s)
Exclusion criteria
* Congenital anomalies likely to affect any primary or secondary endpoints * Uncontrollable air leaks * Hydrops fetalis * Rupture ≥ 3 weeks of the fetal membranes * Evidence of overwhelming bacterial infection at time of randomization * Markedly labile persistent pulmonary hypertension at time of randomization * Profound neurologic manifestations * Sustained postductal SpO₂of \< 87% for ≥ 15 minutes at an FiO₂of 1.00
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Days Receiving Mechanical Ventilation (MV) | 28 days | A patient is not receiving MV if he/she is removed from the mechanical ventilator for ≥ 24 hours. If a patient subsequently requires intubation and MV, the additional time will count as days receiving MV. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Death | 28 days | — |
| Number of Participants With Air Leaks | 28 days | Includes pulmonary interstitial emphysema (PIE), Pneumothorax, Pneumomediastinium, and Pneumopericardium |
Countries
United States
Participant flow
Recruitment details
Recruitment occurred between March 2000 and October 2002. Infants were enrolled from neonatal intensive care units and were randomized to open-label study treatment.
Participants by arm
| Arm | Count |
|---|---|
| Lucinactant Lucinactant via bronchoaveolar lavage | 38 |
| Standard Care Standard Care included the use of oxygen, CMV, sedation, paralysis, vasopressors, and/or alkalinization | 31 |
| Total | 69 |
Baseline characteristics
| Characteristic | Lucinactant | Standard Care | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 38 Participants | 31 Participants | 69 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Gestational Age | 40.0 weeks STANDARD_DEVIATION 1.3 | 39.7 weeks STANDARD_DEVIATION 1.09 | 39.9 weeks STANDARD_DEVIATION 1.21 |
| Region of Enrollment United States | 38 participants | 31 participants | 69 participants |
| Sex: Female, Male Female | 16 Participants | 15 Participants | 31 Participants |
| Sex: Female, Male Male | 22 Participants | 16 Participants | 38 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 36 / 38 | 25 / 31 |
| serious Total, serious adverse events | 23 / 38 | 14 / 31 |
Outcome results
Primary
Number of Days Receiving Mechanical Ventilation (MV)
A patient is not receiving MV if he/she is removed from the mechanical ventilator for ≥ 24 hours. If a patient subsequently requires intubation and MV, the additional time will count as days receiving MV.
Time frame: 28 days
Population: Data from the initial Phase 1/2 trial were used to estimate the number of subjects required for testing the null hypothesis of no difference between treatment groups. A sample size of 100 subjects per group is required to test the hypothesis at a significance level of 0.05 with a power of 80%.~All enrolled infants were analyzed (intent-to-treat).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lucinactant | Number of Days Receiving Mechanical Ventilation (MV) | 10.2 days | Standard Deviation 9.96 |
| Standard Care | Number of Days Receiving Mechanical Ventilation (MV) | 8.1 days | Standard Deviation 8.52 |
Secondary
Incidence of Death
Time frame: 28 days
Population: Data from the initial Phase 1/2 trial were used to estimate the number of subjects required for testing the null hypothesis of no difference between treatment groups. A sample size of 100 subjects per group is required to test the hypothesis at a significance level of 0.05 with a power of 80%.~All enrolled infants were analyzed (intent-to-treat).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lucinactant | Incidence of Death | 0 participants |
| Standard Care | Incidence of Death | 0 participants |
Secondary
Number of Participants With Air Leaks
Includes pulmonary interstitial emphysema (PIE), Pneumothorax, Pneumomediastinium, and Pneumopericardium
Time frame: 28 days
Population: Data from the initial Phase 1/2 trial were used to estimate the number of subjects required for testing the null hypothesis of no difference between treatment groups. A sample size of 100 subjects per group is required to test the hypothesis at a significance level of 0.05 with a power of 80%.~All enrolled infants were analyzed (intent-to-treat).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lucinactant | Number of Participants With Air Leaks | 2 participants |
| Standard Care | Number of Participants With Air Leaks | 0 participants |