Implementing LISA Surfactant in Nigeria

Study Overview
=================
Brief Summary
-----------------
Implement surfactant (BLES®) replacement therapy using the Less Invasive Surfactant Administration technique in six tertiary institutions in Nigeria and evaluate its impact on 72-hour neonatal mortality in premature infants born less than 2000 grams at birth.

Detailed Description
-----------------
Background: In low- and middle-income countries (LMICs), respiratory distress syndrome (RDS) accounts for  45% of all in-hospital neonatal mortality. Surfactant use is limited in LMICs, in part, due to the high cost, the lack of skill to perform laryngoscopy and tracheal intubation, and perhaps a perception that surfactant administration and mechanical ventilation must occur together. In LMICs, continuous positive airway pressure (CPAP) is often the highest mode of respiratory support available, and CPAP failure invariably means death. If Less Invasive Surfactant Administration (LISA) can reduce CPAP failure, as shown in high-income settings, it potentially can reduce prematurity-related neonatal mortality in LMICs. There are, however, no studies on how to safely implement LISA in LMICs. The LISA procedure is novel in LMICs; the procedure is not without risk (severe and minor), laryngoscopy is a difficult skill to acquire, master, and maintain, and the resource limitations in LMICs need consideration while implementing LISA. Hypothesis: Compared to a historical control, introducing non-invasive surfactant administration through the less invasive surfactant administration (LISA) techniques will result in a relative risk reduction of all-cause 72-hour in-hospital mortality by at least 20%. PICO Outline: Population: Preterm infants </= 2 kg with respiratory distress defined by a Downes Respiratory Distress Score of >4, who are spontaneously breathing, and on CPAP. Intervention: Surfactant administered through the less invasive surfactant administration (LISA), technique. Comparator: A historical control of preterm babies </= 2 kg with respiratory distress defined by a Downes Respiratory Distress Score of >4, who are spontaneously breathing, and on CPAP. Outcome measures: Primary Outcome: 72-hour all-cause in-hospital mortality. Secondary outcomes All-cause in-hospital mortality Change in respiratory distress score, pre- to -post interventions.

Official Title
-----------------
Less Invasive Surfactant Administration in Nigeria

Conditions
-----------------
Respiratory Distress Syndrome, Neonatal Death

Intervention / Treatment
-----------------
* Drug: Surfactant


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Newborns with birth weight between 500-2000 grams (determined by birth weight or admission weight if birth weight is unavailable). ≤48 Hours old at recruitment. Spontaneously breathing but have clinical signs of respiratory distress (defined by Anderson Silverman Score (ASS) ≥4 (range 0-10)) and on CPAP. Admitted to the neonatal/newborn units (or special care nurseries). Exclusion Criteria: Any newborn intubated before admission to the neonatal/newborn units. Any newborn infants with a significant congenital abnormality Any preterm infant considered nonviable by the managing clinician.

Ages Eligible for Study
-----------------
Minimum Age: 1 Hour
Maximum Age: 2 Days

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Prospective cohort
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LISA Arm<br>Eligible subjects who have respiratory distress syndrome (Anderson Silverman Score >4) managed on continuous positive airway pressure (CPAP) will receive surfactant via a thin catheter while on CPAP. | Drug: Surfactant<br>* Laryngoscopy is performed, and BLES® surfactant is administered through BLEScath™ (a thin catheter) into the trachea to a spontaneously breathing preterm infant with respiratory distress syndrome who is being managed on CPAP<br>* Other names: Less Invasive Surfactant Administration;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 72-hour mortality | All cause mortality with 72-hours of life | 72 hours of life | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| In-hospital mortality | All cause mortality during hospitalization | Through hospitalization, an average of 1 day to 10 weeks. | 
| Difference in RDS score before and after the procedure. | Change in Anderson Silverman RDS Score before and after intervention (range: 0 to 10) | 6 hours post procedure |