Oxygen Therapy for Children With Moderate Hypoxemia in Malawi (NoGoLo2)

December 18, 2024 updated by: Johns Hopkins University

Oxygen Therapy for Children With Moderate Hypoxemia in Malawi: Pilot Randomized Control Trial

The goal of this pilot clinical trial is to compare standard of care, low-flow oxygen, and high-flow nasal canula oxygen in pediatric patients aged 1-59 months with pneumonia and an oxygen saturation of 90-93% in Malawi. The main question it aims to answer is:

  • Does the protocol for the randomized control trial work well?
  • Can the researchers safely conduct the protocol for the trial?

Participants will be randomly assigned to one of the three groups (normal care without oxygen, low-flow oxygen, and high-flow nasal cannula oxygen) and treated with that therapy in the hospital. Researchers will look at the ability to safely conduct each part of the study.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Pneumonia is the leading infectious cause of under 5-year-old deaths globally and responsible for >50% of deaths in Africa. The World Health Organization (WHO) defines low blood oxygen saturation (SpO2) levels (hypoxemia) as 90%. Hypoxemia is identified in 31% of child pneumonia cases in Africa and is a key marker of elevated mortality risk. When children are hypoxemic, the WHO recommends oxygen treatment. Importantly, the WHO threshold of 90% for hypoxemia was based on concerns over limited oxygen supply and hospital over-crowding in low- and middle-income countries (LMICs), rather than quality evidence. In most LMICs, low oxygen flow is the mainstay of oxygen delivery. Recently, in high-income settings high-flow nasal cannula (HFNC) oxygen has emerged as a safe and effective alternative. HFNC oxygen delivers higher flow warmed, humidified gas via nasal prongs to reverse hypoxemia, and potentially improve outcomes.

Recent evidence challenges whether the WHO & 90% hypoxemia threshold is optimal for identifying all children at higher risk of mortality in LMICs. One meta-analysis from 13 LMICs reported 3.66-fold-higher odds of death (95% confidence interval (CI), 1.42, 9.47) for children with a SpO2 93%. The investigators research from Malawi and Bangladesh established children with pneumonia and SpO2 between 90-93% (moderate hypoxemia) is common, and, compared to higher SpO2 levels, conveys higher mortality risk. To date, African children with a SpO2 90-93% are not recommended for oxygen treatment. Observational data from Malawi found children with moderate hypoxemia and treated with oxygen had higher survival than those referred with a SpO2 90%. Currently, no randomized trials have determined whether low flow oxygen or HFNC oxygen treatment reduces the mortality of children with moderate hypoxemia (SpO2 90-93%) in African LMICs.

Aim 1: Conduct a pilot open label, three armed, parallel, randomized controlled trial (RCT) comparing standard care, low-flow oxygen, and HFNC oxygen for children with clinical pneumonia and a SpO2 90-93% to determine feasibility of a larger trial. The investigators hypothesize it will be feasible to recruit, randomize, treat, and safely follow-up all participants. Children with SpO2 90-93% will be randomized 1:1:1 to standard care without oxygen (controls), low flow oxygen (intervention #1), or HFNC oxygen (intervention #2). The primary outcome will be feasibility, defined as the proportion of enrolled children with 2 protocol violations. Secondary outcomes include consent refusal, intervention efficacy, participant attrition, and safety.

Aim 2: Determine the prevalence of young Malawian children with a SpO2 90-93% at the designated study hospital. The investigators hypothesize a SpO2 90-93% will be common among children presenting to the trial hospital. The investigators will measure the SpO2 of all children under-five years old (not limited to pneumonia cases) presenting to the hospital 1 week per month over 12-months. Conservatively assuming an average volume of 30 children per day, based on prior data, the investigators will generate 1,400 SpO2 measurements.

Study Type

Interventional

Enrollment (Actual)

21

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Malawi
    • Central Region
      • Salima, Central Region, Malawi
        • Salima District Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 1-59 months of age
  • Pneumonia (as defined by the World Health Organization)
  • Oxygen saturation 90-93% without oxygen

Exclusion Criteria:

  • Emergency signs (signs of severe illness as defined by the World Health Organization) including:
  • absent or obstructed breathing,
  • severe respiratory distress,
  • shock,
  • decreased mental status,
  • convulsions, or
  • severe dehydration

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: Standard of Care
Participants will receive pneumonia care per World Health Organization guidelines. If their oxygen saturation falls below 90% after enrollment, they will be treated with low-flow oxygen.
Experimental: Low-flow Oxygen
Participants will be treated with low-flow oxygen to achieve a goal oxygen saturation above 94%
Device: Low flow oxygen
Standard nasal cannula oxygen up to 2 liters/minute
Experimental: High-flow Nasal Cannula Oxygen
Participants will be treated with high-flow nasal cannula oxygen to achieve a goal oxygen saturation above 94%.
Device: High-flow nasal cannula oxygen
High-flow nasal cannula with heating and humidification up to 2 liters/kilogram/minute

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Feasibility of study protocol as assessed by protocol violations
Time Frame: Enrollment up to 14 days
Determine overall protocol fidelity, defined as the percentage of enrolled children with < 2 protocol violations, of an open-label, three arm randomized controlled trial comparing low-flow and high-flow nasal cannula (HFNC) oxygen to standard of care without oxygen therapy
Enrollment up to 14 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Caregiver Trial Acceptability
Time Frame: Day of screening and enrollment
Determine caregiver trial acceptability, defined as the percentage of caregivers of eligible children who consent to study participation.
Day of screening and enrollment
Feasibility of screening and enrollment as assessed by percentage of inclusion and exclusion violations
Time Frame: Day of screening and enrollment
Determine the feasibility of screening and enrollment, defined as the percentage of enrolled children with no inclusion or exclusion criteria violations.
Day of screening and enrollment
Feasibility of randomization as assessed by percentage of children receiving intervention
Time Frame: 1 hour after randomization
Determine feasibility of randomization, defined as percentage of children actively receiving the assigned intervention within 1 hours of randomization
1 hour after randomization
Fidelity to treatment failure study definition as assessed by percentage of children with correct treatment failure classification
Time Frame: Enrollment up to 14 days
Determine fidelity to treatment failure study definition, defined as the percentage of children with a correct treatment failure classification
Enrollment up to 14 days
Fidelity to respiratory supportive care protocol as assessed by percentage of children without a respiratory support protocol violation
Time Frame: Enrollment up to 14 days
Determine fidelity to respiratory supportive care protocol, defined as the proportion of children without a respiratory support protocol violation
Enrollment up to 14 days
Feasibility of at home follow up as assessed by percentage of participants followed up at home
Time Frame: Enrollment up to 14 days
Determine feasibility of at home follow up defined as percentage of patients successfully followed up at home with assessment of vital status
Enrollment up to 14 days

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Treatment failure rate
Time Frame: Enrollment up to 14 days
Determine point estimates and 95% confidence intervals for treatment failure rate for standard of care, conventional low-flow oxygen, and HFNC oxygen arms for children with WHO-defined pneumonia and moderate hypoxemia
Enrollment up to 14 days
Mortality rate
Time Frame: Enrollment up to 14 days
Determine point estimates and 95% confidence intervals for mortality rate for standard of care, conventional low-flow oxygen, and HFNC oxygen arms for children with WHO-defined pneumonia and moderate hypoxemia
Enrollment up to 14 days
Number of Serious Adverse Events
Time Frame: Enrollment up to 14 days
Determine point estimate and 95% confidence interval for the rate of serious adverse events (SAEs) for standard of care, conventional low-flow oxygen, and HFNC oxygen arms for children with WHO-defined pneumonia and moderate hypoxemia
Enrollment up to 14 days
Hospital length of stay (days)
Time Frame: Enrollment through hospital discharge up to 30 days
Determine mean hospital length of stay with standard deviation for standard of care, conventional low-flow oxygen, and HFNC oxygen arms for children with World Health Organization (WHO)-defined pneumonia and moderate hypoxemia
Enrollment through hospital discharge up to 30 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Johns Hopkins University

Collaborators

Thrasher Research Fund

Investigators

  • Principal Investigator: Eric E McCollom, MD, MPH, Johns Hopkins School of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 15, 2024

Primary Completion (Actual)

November 30, 2024

Study Completion (Actual)

November 30, 2024

Study Registration Dates

First Submitted

December 6, 2023

First Submitted That Met QC Criteria

December 18, 2023

First Posted (Actual)

December 20, 2023

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

December 18, 2024

Last Verified

December 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB00421624

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

The research proposed is a pilot randomized, open-label trial of acute lower respiratory infection with moderate hypoxemia oxygen use in Malawi. The pilot trial will enroll 21 participants with a primary outcome of study feasibility. The datasets will report de-identified patient outcomes including mortality, hospital length of stay, and treatment failure as well as trial feasibility and acceptability data. The shared format of data will be .csv files.

IPD Sharing Time Frame

Data will be provided at the time of the primary outcome publication(s) for a period of at least 10 years.

IPD Sharing Access Criteria

Publicly shared data will be deposited in an open access repository that meets the specifications required by the NIH. The selected repository will provide metadata, unique identifiers, and data access for at least 10 years. Use of keywords will allow for findability using searches. Access to data will be controlled and limited to qualified investigators who sign a data use agreement and provide a reasonable research question for application to the data. Data requests will require at least a description of the research, objective, design, analysis plan that includes data safeguards, publicly available research use statement, documentation of institutional Review Board (IRB) review and approval. The open access repository will review the request and has final authority for deciding on access to the data. If the study is active, then

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • ANALYTIC_CODE

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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