Principal Investigator: Mohammod Jobayer Chisti

Research Protocol Title: Feasibility and Acceptability Followed by Effectiveness of Bubble Continuous Positive Airway Pressure (bCPAP) for Treatment of Children aged 1-59 months with Severe Pneumonia in Ethiopia: A Cluster Randomized Controlled Clinical Trial

Proposed start date: 1st July 2018, Estimated end date: 31st December 2022

Background: Feasibility and acceptability followed by effectiveness of bubble continuous positive airway pressure (CPAP) were not evaluated in childhood severe pneumonia in developing countries at a larger scale.

Objectives:

Stages I and II

• To assess the feasibility and acceptability (not only by patients' care-givers but also by physicians and nurses) of bubble CPAP in treating childhood severe pneumonia in two tertiary hospitals in Stage I and in two district hospitals in Stage II
• To record adverse events following use of bubble CPAP in these settings
• To understand how much resource and time are needed to institutionalize and maintain bubble CPAP as a routine practice in the health system

Stage III:

• To determine therapeutic efficacy/effectiveness of bubble CPAP compared to WHO standard low flow oxygen in reducing treatment failure in children admitted to hospitals with severe pneumonia and hypoxemia
• To determine therapeutic effectiveness of bubble CPAP compared to WHO standard low flow oxygen in reducing treatment failure & mortality in children aged 1-12 months admitted to hospitals with severe pneumonia and hypoxemia
• To record adverse events (pneumothorax, abdominal distension, nasal trauma, aspiration pneumonia) encountered.

Methodology:

Cluster randomized controlled clinical trial

Methodology:

1. Stages I and II: Feasibility/demonstration stage will be done as an internal pilot in 3 hospitals

   a. Current treatment practice, facilities, and operational challenges will be evaluated for the introduction, clinical use and maintenance of bubble CPAP

2. Stage III: Implementation of bubble CPAP will be done in 12 hospitals a. It will be done following a cluster randomized design

Data collection-socio-demographic and clinical data will be collected using structured questionnaire by trained nurses and physicians.

Research Site:

St. Paulos Millennium Medical College, Yekatit 12 and Tikur Anbessa Specialized hospitals, 14 district hospitals

Number of Participants/Patients:

Stage I-30 children in each tertiary hospital (this stage has completed and we enrolled 49 children from two tertiary hospitals; these 49 enrolled children took double of our anticipated time {4 months}) Stage II- 20 children in each general hospital (2 general/district hospitals, we have enrolled total 40 children from this two hospitals from January 2020 to July 2020, which included COVID-19 period) Stage III-1240 children in 12 general/district hospitals (620 in bubble CPAP arm and 620 in WHO standard low flow arm; each hospital will be the cluster and 6 will be randomized to each arm)

Main Inclusion Criteria:

• Age between 1 month and 59 months
• Meet WHO clinical criteria for severe pneumonia with hypoxemia
• Hypoxemia (Oxygen saturation <90% in room air)
• Parent/guardian gives informed consent to participate in the study

Statistical Analysis:

• STATA -14: for initial two phases descriptive analysis of level of feasibility and acceptability will be performed
• For the phase III: We shall follow the principle of intention to treat. --Treatment failure and/or death will be analyzed using χ² or Fisher's exact tests as appropriate.
• Primary and secondary outcomes will be compared by calculating relative risks (RRs) and their 95% confidence intervals.
• Log-linear binomial regression will be applied to adjust for covariates to evaluate the true impact of bubble CPAP in evaluating primary and secondary outcomes and to adjust for baseline differences.
• Continuous variables will be analyzed using the Student t-test or the Mann-Whitney test as appropriate.

Study Duration:

48 months.

Inclusion Criteria:

• Age between 1 month and 59 months,
• Meet WHO clinical criteria for severe pneumonia with hypoxemia.
• Oxygen saturation <90% despite standard flow oxygen therapy
• Parent/guardian gives informed consent to participate in the study

Exclusion Criteria:

• Known congenital heart disease, asthma, or upper -airway obstruction
• Tracheostomy
• Pneumothorax
• Needs mechanical ventilation for any specific reason as decided by the clinician

We will share the final outcome after completing the study

As it was an open-labeled randomized controlled clinical trial, there was no masking in any intervention.