Surfactant Lavage vs. Bolus Surfactant in Neonates With Meconium Aspiration

Study Overview
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Brief Summary
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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
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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.

Official Title
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Surfactant Lavage vs. Bolus Surfactant in Neonates With Meconium Aspiration

Conditions
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Meconium Aspiration Syndrome

Intervention / Treatment
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* Drug: Bovine Lipid Extract Surfactant (administered by lavage)
* Drug: Bovine Lipid Extract Surfactant (administered by bolus)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 1 Hour
Maximum Age: 24 Hours

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Bovine Lipid Extract Surfactant (administered by lavage)|nan|
|Drug: Bovine Lipid Extract Surfactant (administered by bolus)|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| % 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 | Measure Description | Time Frame |
| --- | --- | --- |
| % 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 |  |  | 
| mortality |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Meconium Aspiration Syndrome, Surfactant, Bronchoalveolar Lavage, newborns