Clinical trial NCT00312507: Surfactant Lavage vs. Bolus Surfactant in Neonates With Meconium Aspiration
Official title: Surfactant Lavage vs. Bolus Surfactant in Neonates With Meconium Aspiration
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Meconium Aspiration Syndrome
Keywords: Meconium Aspiration Syndrome
Surfactant
Bronchoalveolar Lavage
newborns
Lead sponsor: The Hospital for Sick Children
Sponsor class: OTHER
First posted: 2006-04-10
Enrollment: 20
Sex: ALL
Minimum age (years): 1
Maximum age (years): 24
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).

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.

Eligibility criteria: 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

Primary outcomes:
measure: % change in oxygenation indices from baseline to 1 and 6 h following treatment
measure: % change in dynamic pulmonary compliance from baseline to 1 and 6 h following treatment
measure: % change in pulmonary artery pressure from baseline to 1 and 6 h following treatment
measure: measures of efficacy of ventilation and oxygenation at 1 h and 6 h following treatment
measure: cardiac function by echocardiography at 6 hours following treatment
Secondary outcomes:
measure: % change in oxygenation indices, dynamic pulmonary compliance and pulmonary vascular resistance from baseline to 12, 24 and 48 h following treatment
measure: measures of efficiency of ventilation and oxygenation at 12, 24 and 48 h following treatment
measure: duration of mechanical ventilation, defined as the cumulative time of mechanical ventilation
measure: length of time on CPAP
measure: length of time with oxygen supplementation
measure: length of time on inotropes and maximum inotropic score.
measure: need for and length of use of NO
measure: need for and length of use of ECMO
measure: time to full enteral feeds
measure: attainment of exit criteria
measure: development of significant pulmonary hemorrhage
measure: development of significant intracranial hemorrhage
measure: development of tension pneumothorax requiring drainage
measure: need for repeat surfactant
measure: length of stay in a level III NICU
measure: mortality
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: The Hospital for Sick Children
state: Ontario
Study officials:
affiliation: The Hospital for Sick Children
name: Patrick McNamara, MD
role: PRINCIPAL_INVESTIGATOR
References: