Feasibility and Acceptability Followed by Effectiveness of bCPAP for Treatment of Children Aged 1-59 Months With Severe Pneumonia in Ethiopia

Study Overview
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Brief Summary
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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.

Detailed Description
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Methodology: Cluster randomized controlled clinical trial Methodology: 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 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.

Official Title
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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

Conditions
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Severe Pneumonia

Intervention / Treatment
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* Device: Bubble CPAP
* Device: Low flow oxygen


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 1 Month
Maximum Age: 59 Months

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
Interventional Model Description: Children aged 1-59 months with Severe Pneumonia in Ethiopia, divided in two arms; one arm will get bCPAP other arm will get WHO recommended low flow oxygen.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Bubble CPAP<br>6 hospitals will be selected randomly for this arm | Device: Bubble CPAP<br>* To see the effectiveness of Bubble Continuous Positive Airway Pressure (bCPAP) in children with severe pneumonia<br>|
| Active Comparator: Low flow oxygen<br>6 hospitals will be selected for low flow oxygen therapy | Device: Low flow oxygen<br>* To see the effectiveness of low flow oxygen in children with severe pneumonia<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| For stage I and II feasibility and acceptability of bubble CPAP in two tertiary and two district hospitals will be measured in number and reported in percentage | Patient level and health professional level challenge is the outcome of phase I and II. All will be measured in number and reported in percentage. For stage I and II: Primary outcome: operational challenges that may include availability of pulse oxymetry, IV cannula, IV antibiotics, oxygen supply system and nasal catheters for treating severe pneumonia Secondary outcomes: prevalence of severe pneumonia associated hypoxemia, their treatment practices, adverse events, mortality and treatment failure | 7 months | 
| For stage III: Primary outcome: Treatment failure | According to this protocol treatment failure will be declared if the following criteria are met: A. Presence of severe hypoxemia (SpO2<85%) at any time after at least one hour of intervention plus severe respiratory distress when the child is receiving BCPAP/LF OR, B. If the patient developed the indication of mechanical ventilation when the child is receiving BCPAP/LF OR, C. If the patient died during hospitalization OR, D. If the patient left against medical advice (LAMA) due to lack of improvement or deterioration of the child during hospitalization All will be measured in number and reported in percentage. | 12-18 months (Mid April 2021 to Mid October 2022) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary outcomes: • Death • Adverse events (pneumothorax, abdominal distension, nasal trauma, aspiration pneumonia ) encountered | All will be measured in number and reported in percentage. | 12-18 months (Mid April 2021 to Mid October 2022) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bubble CPAP, Young Children, Severe Pneumonia, Hypoxemia, Treatment failure, Mortality