Surfactant Lavage vs. Bolus Surfactant in Neonates With Meconium Aspiration

The objective of this pilot study is to examine the feasibility and safety of performing a larger trial to assess outcomes following treatment of meconium aspiration syndrome with surfactant lavage compared to bolus surfactant. Specifically, we will determine if surfactant lavage results in a more rapid improvement in physiologic outcomes (e.g. pulmonary compliance), as well as clinical outcomes (e.g. length of time on mechanical ventilation).

Study Overview

• Status: Unknown
• Conditions: Meconium Aspiration Syndrome
• Intervention / Treatment: Drug: Bovine Lipid Extract Surfactant (administered by lavage); Drug: Bovine Lipid Extract Surfactant (administered by bolus)

Detailed Description

Meconium-stained amniotic fluid occurs in about 5 to 20% of all births in the United States, with meconium aspiration syndrome occuring in approximately 5% of these infants. In this disease process, meconium is believed to mechanically obstruct the airways, causing a chemical pneumonitis and inactivate surfactant. Approximately one-third of these babies need mechanical ventilation and approximately 5% die. Since 1990 surfactant has been the standard of care for treatment of respiratory distress syndrome. Pulmonary compliance and gas exchange often improve rapidly after administration of surfactant. Its use has led to significantly reduced mortality rates and improved short-term respiratory function. There is evidence to support its use in other neonatal respiratory disorders where there is dysfunction or inactivation of surfactant. Its use in meconium aspiration syndrome is the most well-studied alternate use to date. The Canadian Pediatric Society's (2005) position statement recommends that infants with meconium aspiration syndrome who are intubated and require more than 50% oxygen should receive exogenous surfactant therapy.

Studies in both animals and humans suggest that surfactant helps in meconium aspiration, either administered as a bolus or as a lavage. There have been no trials to date comparing the efficacy of surfactant lavage to bolus surfactant in human neonates with meconium aspiration or examining the physiologic effects of surfactant, given as either a bolus or lavage, in the treatment of meconium aspiration syndrome. This study will assess the relative efficacy of these two methods of administering surfactant and their effect on physiologic and clinical outcomes.

• Study Type: Interventional
• Enrollment: 20
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Patrick McNamara, MD; Phone Number: 416-813-5773; Email: patrick.mcnamara@sickkids.ca

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X8
      • Recruiting
      • The Hospital for Sick Children
      • Contact: Patrick McNamara, MD; Phone Number: 416 813 5773; Email: patrick.mcnamara@sickkids.ca
      • Principal Investigator: Patrick McNamara, MD
      • Sub-Investigator: Simone Vaz, MD
      • Sub-Investigator: Hilary Whyte, MD
      • Sub-Investigator: Jaques Belik, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 hour to 1 day (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• infants ≥ 36 weeks gestational age with evidence of meconium aspiration syndrome
• respiratory support (ventilator or CPAP) within 6 h of birth
• enrolment within 24 h of birth
• significant difficulty with oxygenation, as indicated by an oxygenation index (OI) > 15, where OI = (FiO2 x MAP) / PaO2 and MAP is the mean airway pressure
• presence of an arterial line

Exclusion Criteria:

• major congenital anomalies
• known antenatal diagnosis of significant congenital heart disease (diagnosis other than patent foramen ovale, patent ductus arteriosus or small ventricular septal defect)
• infants with a maternal history of oligohydramnios and physical features consistent with the diagnosis
• surfactant administration prior to enrolment
• hemodynamic instability defined as intractable hypotension on more than 2 inotropes
• significant pulmonary hemorrhage, defined as pulmonary hemorrhage in association with a 30% (absolute) increase in FiO2 and radiologic changes consistent with pulmonary hemorrhage
• significant intracranial hemorrhage, defined as a unilateral or bilateral Grade III or IV intraventricular hemorrhage or a large intracranial, non-intraventricular hemorrhage
• significant illness meeting ECMO criteria with an OI > 40
• infants in whom withdrawal of intensive care is likely

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

What is the study measuring?

Primary Outcome Measures

Outcome Measure
% change in oxygenation indices from baseline to 1 and 6 h following treatment
% change in dynamic pulmonary compliance from baseline to 1 and 6 h following treatment
% change in pulmonary artery pressure from baseline to 1 and 6 h following treatment
measures of efficacy of ventilation and oxygenation at 1 h and 6 h following treatment
cardiac function by echocardiography at 6 hours following treatment

Secondary Outcome Measures

Outcome Measure
mortality
% change in oxygenation indices, dynamic pulmonary compliance and pulmonary vascular resistance from baseline to 12, 24 and 48 h following treatment
measures of efficiency of ventilation and oxygenation at 12, 24 and 48 h following treatment
duration of mechanical ventilation, defined as the cumulative time of mechanical ventilation
length of time on CPAP
length of time with oxygen supplementation
length of time on inotropes and maximum inotropic score.
need for and length of use of NO
need for and length of use of ECMO
time to full enteral feeds
attainment of exit criteria
development of significant pulmonary hemorrhage
development of significant intracranial hemorrhage
development of tension pneumothorax requiring drainage
need for repeat surfactant
length of stay in a level III NICU

Collaborators and Investigators

• Sponsor: The Hospital for Sick Children
• Investigators: Principal Investigator: Patrick McNamara, MD, The Hospital for Sick Children

Study record dates

Study Major Dates

• Study Start: April 1, 2006

Study Registration Dates

• First Submitted: April 6, 2006
• First Submitted That Met QC Criteria: April 6, 2006
• First Posted (Estimate): April 10, 2006

Study Record Updates

• Last Update Posted (Estimate): October 17, 2006
• Last Update Submitted That Met QC Criteria: October 16, 2006
• Last Verified: October 1, 2006

More Information

Terms related to this study

• Keywords: Surfactant; newborns; Bronchoalveolar Lavage; 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: 1000007730