| Protocol No: | ECCT/25/04/03 | Date of Protocol: | 25-10-2024 |
| Study Title: | Pragmatic Evaluation of Therapies to Enhance Respiratory Management in Preterm Infants in Africa |
| Study Objectives: |
Primary aims
Determine the effect of Vayu bCPAP (Bubble Continuous Positive Airway Pressure) + Caffeine + LISA (Less Invasive Surfactant Administration) vs. Vayu bCPAP + Caffeine on hospital survival.
Secondary aims
The incidence of major neonatal complications, including:
- Neonatal sepsis: Incidence of a positive blood culture during hospitalization.
- Incidence and highest grade of intraventricular haemorrhage (IVH): Assessed by ultrasound scan between DOL 3 and 7.
- Retinopathy of prematurity (ROP): Assessed as the worst stage by an ophthalmologist in patients <1500 grams at birth.
- Bronchopulmonary dysplasia (BPD): Defined as continued use of supplemental oxygen at 28 days of life.
- Surgical Necrotizing Enterocolitis (NEC stage IV): Defined as the need for any surgical intervention for a patient with clinical signs of necrotizing enterocolitis.
- Determine the incidence of clinically diagnosed pneumothorax: Diagnosed with a positive transillumination sign.
- Determine the effect of Vayu bCPAP + Caffeine + LISA vs. current standard respiratory support on hospital survival.
Tertiary aims
- Evaluate the implementation of the intervention bundle using the RE-AIM Framework.
o Reach: Measured by evaluating the proportion of eligible subjects successfully treated with the intervention.
o Adoption: Measured by providers' perception of the intervention (s) and implementation strategy.
o Implementation fidelity: Measured by the degree of adherence to the implementation strategy.
- Determine the cost-effectiveness of the individual and bundled intervention.
Exploratory aims
During the standardization phase, we will explore the impact of Vayu bCPAP and caffeine citrate on:
- The difference in Silverman Anderson Score.
- The difference in the 7-day apnoea of prematurity incidence. - The difference in the hospital survival. |
| Laymans Summary: |
Over the past 30 years, there has been great progress in reducing child deaths worldwide. However, in many parts of sub-Saharan Africa, newborn deaths remain high, with premature birth being a leading cause. Babies born too early often struggle to breathe because their lungs are not fully matured. In high-income countries, these babies receive advanced treatments like caffeine therapy and surfactant therapy to help them breathe, but in many low- and middle-income countries (LMICs), these treatments are either unavailable, too expensive, or not well studied.
One of the main breathing problems faced by premature babies is Respiratory Distress Syndrome (RDS), which makes it difficult for them to get enough oxygen. Many hospitals in Sub-Saharan Africa do not have access to ventilators (machines that help babies breathe), so they rely on a simpler and more affordable breathing support device called CPAP (Continuous Positive Airway Pressure). However, if CPAP alone is not enough, these babies often do not survive because alternative treatments are limited.
This study aims to find the best way to help premature babies with breathing difficulties survive in hospitals in sub-Saharan Africa. We will test a low-cost CPAP device called Vayu bCPAP, which is already available in some hospitals, and combine it with caffeine therapy, a medication that helps babies breathe better. We will also study whether adding a gentler method of giving surfactant therapy, known as Less Invasive Surfactant Administration (LISA), improves survival rates.
The study will be done in two phases. In the first phase, hospitals will standardize the use of Vayu bCPAP and caffeine therapy for premature babies. In the second phase, we will introduce LISA surfactant therapy in a step-by-step manner and compare the results to see if this approach reduces deaths. The study will focus on premature babies born between 24 and 35 weeks or weighing 750–2000 grams, who are at high risk of breathing problems.
By conducting this study, we hope to provide strong scientific evidence on the best way to treat premature babies with breathing difficulties in African hospitals. If successful, this research could help improve newborn care in many low-resource settings and save thousands of lives.
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| Abstract of Study: |
Background
Significant progress in improving child survival has led to a 59% decline in global childhood mortality from 1990 to 2021. However, to achieve the 2030 Sustainable Development Goal (≤12 deaths per 1000 live births), more efforts are needed, particularly in high-burden regions like sub-Saharan Africa (SSA). SSA has the highest neonatal mortality rate (27 per 1000 live births), accounting for 43% of global newborn deaths, with prematurity complications and infections as leading causes.
Respiratory distress syndrome (RDS) is the primary cause of preterm mortality in low- and middle-income countries (LMICs), responsible for 45% of preterm deaths compared to just 2% in high-income countries (HICs). The World Health Organization (WHO) recommends caffeine citrate for apnea of prematurity and surfactant for RDS, both proven effective in HICs. However, knowledge gaps exist in implementing these therapies in LMICs, particularly in SSA, where high-quality studies on their impact remain lacking.
Justification
In sub-Saharan Africa (SSA), ventilator use for preterm newborns with RDS is limited due to cost, making CPAP the highest level of respiratory support. Unlike in high-income countries (HICs), CPAP failure in low- and middle-income countries (LMICs) often leads to death. Locally customized CPAP devices are untested and pose risks, while standardized low-cost CPAP options exist but remain understudied in these settings. Caffeine citrate, the preferred treatment for apnea of prematurity (AOP), has proven benefits but has not been evaluated where CPAP is the primary respiratory support. Similarly, Less Invasive Surfactant Administration (LISA), which reduces CPAP failure and mortality in HICs, lacks evidence in LMICs with limited access to ventilators. Further research is needed to assess the impact of standardized CPAP, caffeine therapy, and LISA in resource-limited settings.
Objectives and Endpoints
Primary Objective:
To determine the effect of Vayu bCPAP + Caffeine + LISA vs. Vayu bCPAP + Caffeine on hospital survival of preterm neonates.
Corresponding Endpoint:
The all-cause mortality before hospital discharge that will be obtained from hospital records.
Overall design and Study population
The study will use an effectiveness-implementation hybrid type 1 design with two phases. Phase one will follow a prospective cohort design, standardizing the use of Vayu bCPAP and caffeine. In phase two, a stepped-wedge cluster randomized controlled trial will be conducted to implement the LISA procedure for surfactant administration. The study population will be preterm neonates with a birth weight of 750 - 2000g or gestational age between 24 - 35 weeks with RDS.
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