Phase III Randomized Study of Lucinactant in Full Term Newborn Infants With Meconium Aspiration Syndrome

A Multicenter, Randomized, Controlled Trial Comparing the Safety and Effectiveness of Bronchoalveolar Lavage With Lucinactant to Standard Care for the Treatment of the Meconium Aspriation Syndrome (MAS) in Newborn Infants

OBJECTIVES:

Evaluate the safety and efficacy of lucinactant administered by bronchoalveolar lavage (BAL) in the treatment of meconium aspiration syndrome (MAS) in newborn infants.

Study Overview

• Status: Terminated
• Conditions: Meconium Aspiration
• Intervention / Treatment: Drug: Lucinactant; Other: Standard Care

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.

• Study Type: Interventional
• Enrollment (Actual): 69
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Warrington, Pennsylvania, United States, 18976
      • Discovery Laboratories, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 2 days (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lucinactant; Lucinactant via bronchoaveolar lavage	Drug: Lucinactant; 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.; Other Names: KL₄Surfactant; Surfactant
Other: Standard Care; Standard Care included the use of oxygen, CMV, sedation, paralysis, vasopressors, and/or alkalinization	Other: Standard 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; Other Names: Negative Control

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Death		28 days
Number of Participants With Air Leaks	Includes pulmonary interstitial emphysema (PIE), Pneumothorax, Pneumomediastinium, and Pneumopericardium	28 days

Collaborators and Investigators

• Sponsor: Windtree Therapeutics
• Investigators: Study Chair: Thomas E Wiswell, Windtree Therapeutics

Study record dates

Study Major Dates

• Study Start: March 1, 2000
• Primary Completion (Actual): November 1, 2002
• Study Completion (Actual): November 1, 2004

Study Registration Dates

• First Submitted: October 18, 1999
• First Submitted That Met QC Criteria: October 18, 1999
• First Posted (Estimate): October 19, 1999

Study Record Updates

• Last Update Posted (Estimate): May 3, 2012
• Last Update Submitted That Met QC Criteria: May 1, 2012
• Last Verified: May 1, 2012

More Information

Terms related to this study

• Keywords: rare disease; cardiovascular and respiratory diseases; meconium aspiration syndrome
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Infant, Newborn, Diseases; Fetal Diseases; Pregnancy Complications; Lung Injury; Meconium Aspiration Syndrome; Respiratory System Agents; Pulmonary Surfactants
• Other Study ID Numbers: KL4-MAS-03; FD-R-001938 (Other Grant/Funding Number: US Department of Health and Human Services)