Oxygen Therapy for Children With Moderate Hypoxemia in Malawi

NCT06176664 | Completed

• 1 other identifier: IRB00421624
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Pneumonia

Keywords

Pneumonia; High flow nasal cannula oxygen; Oxygen; Low and Middle Income Countries; pediatrics

Outcome Measures

Primary Outcomes (1)

• Feasibility of study protocol as assessed by protocol violations

  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 Outcomes (6)

• Caregiver Trial Acceptability

  Day of screening and enrollment

• Feasibility of screening and enrollment as assessed by percentage of inclusion and exclusion violations

  Day of screening and enrollment

• Feasibility of randomization as assessed by percentage of children receiving intervention

  1 hour after randomization

• Fidelity to treatment failure study definition as assessed by percentage of children with 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

  Enrollment up to 14 days

Other Outcomes (4)

• Treatment failure rate

  Enrollment up to 14 days

• Mortality rate

  Enrollment up to 14 days

• Number of Serious Adverse Events

  Enrollment up to 14 days

Study Arms (3)

Standard of Care

NO INTERVENTION

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.

Low-flow Oxygen

EXPERIMENTAL

Participants will be treated with low-flow oxygen to achieve a goal oxygen saturation above 94%

Device: Low flow oxygen

High-flow Nasal Cannula Oxygen

EXPERIMENTAL

Participants will be treated with high-flow nasal cannula oxygen to achieve a goal oxygen saturation above 94%.

Device: High-flow nasal cannula oxygen

Interventions

Low flow oxygen DEVICE

Standard nasal cannula oxygen up to 2 liters/minute

Low-flow Oxygen

High-flow nasal cannula oxygen DEVICE

High-flow nasal cannula with heating and humidification up to 2 liters/kilogram/minute

High-flow Nasal Cannula Oxygen

Eligibility Criteria

• Age: 1 Month - 59 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Johns Hopkins University: lead
• Thrasher Research Fund: collaborator

Study Sites (1)

Salima District Hospital

Salima, Central Region, Malawi

Location

Related Publications (24)

• Tortosa F, Izcovich A, Carrasco G, Varone G, Haluska P, Sanguine V. High-flow oxygen nasal cannula for treating acute bronchiolitis in infants: A systematic review and meta-analysis. Medwave. 2021 May 12;21(4):e8190. doi: 10.5867/medwave.2021.04.8190. English, Spanish.

  PMID: 34086669 BACKGROUND

• Luo J, Duke T, Chisti MJ, Kepreotes E, Kalinowski V, Li J. Efficacy of High-Flow Nasal Cannula vs Standard Oxygen Therapy or Nasal Continuous Positive Airway Pressure in Children with Respiratory Distress: A Meta-Analysis. J Pediatr. 2019 Dec;215:199-208.e8. doi: 10.1016/j.jpeds.2019.07.059. Epub 2019 Sep 27.

  PMID: 31570155 BACKGROUND

• Lin J, Zhang Y, Xiong L, Liu S, Gong C, Dai J. High-flow nasal cannula therapy for children with bronchiolitis: a systematic review and meta-analysis. Arch Dis Child. 2019 Jun;104(6):564-576. doi: 10.1136/archdischild-2018-315846. Epub 2019 Jan 17.

  PMID: 30655267 BACKGROUND

• Kawaguchi A, Yasui Y, deCaen A, Garros D. The Clinical Impact of Heated Humidified High-Flow Nasal Cannula on Pediatric Respiratory Distress. Pediatr Crit Care Med. 2017 Feb;18(2):112-119. doi: 10.1097/PCC.0000000000000985.

  PMID: 27741041 BACKGROUND

• McKiernan C, Chua LC, Visintainer PF, Allen H. High flow nasal cannulae therapy in infants with bronchiolitis. J Pediatr. 2010 Apr;156(4):634-8. doi: 10.1016/j.jpeds.2009.10.039. Epub 2009 Dec 29.

  PMID: 20036376 BACKGROUND

• Moreel L, Proesmans M. High flow nasal cannula as respiratory support in treating infant bronchiolitis: a systematic review. Eur J Pediatr. 2020 May;179(5):711-718. doi: 10.1007/s00431-020-03637-0. Epub 2020 Mar 31.

  PMID: 32232547 BACKGROUND

• Hutchings FA, Hilliard TN, Davis PJ. Heated humidified high-flow nasal cannula therapy in children. Arch Dis Child. 2015 Jun;100(6):571-5. doi: 10.1136/archdischild-2014-306590. Epub 2014 Dec 1.

  PMID: 25452315 BACKGROUND

• McCollum ED, Mvalo T, Eckerle M, Smith AG, Kondowe D, Makonokaya D, Vaidya D, Billioux V, Chalira A, Lufesi N, Mofolo I, Hosseinipour M. Bubble continuous positive airway pressure for children with high-risk conditions and severe pneumonia in Malawi: an open label, randomised, controlled trial. Lancet Respir Med. 2019 Nov;7(11):964-974. doi: 10.1016/S2213-2600(19)30243-7. Epub 2019 Sep 24.

  PMID: 31562059 BACKGROUND

• Chaparro CM, Suchdev PS. Anemia epidemiology, pathophysiology, and etiology in low- and middle-income countries. Ann N Y Acad Sci. 2019 Aug;1450(1):15-31. doi: 10.1111/nyas.14092. Epub 2019 Apr 22.

  PMID: 31008520 BACKGROUND

• Allardet-Servent J, Sicard G, Metz V, Chiche L. Benefits and risks of oxygen therapy during acute medical illness: Just a matter of dose! Rev Med Interne. 2019 Oct;40(10):670-676. doi: 10.1016/j.revmed.2019.04.003. Epub 2019 May 1.

  PMID: 31054779 BACKGROUND

• McCollum ED, Ahmed S, Roy AD, Chowdhury NH, Schuh HB, Rizvi SJR, Hanif AAM, Khan AM, Mahmud A, Pervaiz F, Harrison M, Reller ME, Simmons N, Quaiyum A, Begum N, Santosham M, Checkley W, Moulton LH, Baqui AH; Projahnmo Study Group in Bangladesh. Effectiveness of the 10-valent pneumococcal conjugate vaccine against radiographic pneumonia among children in rural Bangladesh: A case-control study. Vaccine. 2020 Sep 29;38(42):6508-6516. doi: 10.1016/j.vaccine.2020.08.035. Epub 2020 Aug 29.

  PMID: 32873404 BACKGROUND

• Colbourn T, King C, Beard J, Phiri T, Mdala M, Zadutsa B, Makwenda C, Costello A, Lufesi N, Mwansambo C, Nambiar B, Hooli S, French N, Bar Zeev N, Qazi SA, Bin Nisar Y, McCollum ED. Predictive value of pulse oximetry for mortality in infants and children presenting to primary care with clinical pneumonia in rural Malawi: A data linkage study. PLoS Med. 2020 Oct 23;17(10):e1003300. doi: 10.1371/journal.pmed.1003300. eCollection 2020 Oct.

  PMID: 33095763 BACKGROUND

• Rahman AE, Hossain AT, Nair H, Chisti MJ, Dockrell D, Arifeen SE, Campbell H. Prevalence of hypoxaemia in children with pneumonia in low-income and middle-income countries: a systematic review and meta-analysis. Lancet Glob Health. 2022 Mar;10(3):e348-e359. doi: 10.1016/S2214-109X(21)00586-6.

  PMID: 35180418 BACKGROUND

• McCollum ED, Ginsburg AS. Outpatient Management of Children With World Health Organization Chest Indrawing Pneumonia: Implementation Risks and Proposed Solutions. Clin Infect Dis. 2017 Oct 16;65(9):1560-1564. doi: 10.1093/cid/cix543.

  PMID: 29020216 BACKGROUND

• Hooli S, Colbourn T, Lufesi N, Costello A, Nambiar B, Thammasitboon S, Makwenda C, Mwansambo C, McCollum ED, King C. Predicting Hospitalised Paediatric Pneumonia Mortality Risk: An External Validation of RISC and mRISC, and Local Tool Development (RISC-Malawi) from Malawi. PLoS One. 2016 Dec 28;11(12):e0168126. doi: 10.1371/journal.pone.0168126. eCollection 2016.

  PMID: 28030608 BACKGROUND

• Hooli S, King C, Zadutsa B, Nambiar B, Makwenda C, Masache G, Lufesi N, Mwansambo C, Malla L, Costello A, Colbourn T, McCollum ED. The Epidemiology of Hypoxemic Pneumonia among Young Infants in Malawi. Am J Trop Med Hyg. 2020 Mar;102(3):676-683. doi: 10.4269/ajtmh.19-0516.

  PMID: 31971153 BACKGROUND

• King C, Zadutsa B, Banda L, Phiri E, McCollum ED, Langton J, Desmond N, Qazi SA, Nisar YB, Makwenda C, Hildenwall H. Prospective cohort study of referred Malawian children and their survival by hypoxaemia and hypoglycaemia status. Bull World Health Organ. 2022 May 1;100(5):302-314B. doi: 10.2471/BLT.21.287265. Epub 2022 Mar 25.

  PMID: 35521039 BACKGROUND

• Subhi R, Adamson M, Campbell H, Weber M, Smith K, Duke T; Hypoxaemia in Developing Countries Study Group. The prevalence of hypoxaemia among ill children in developing countries: a systematic review. Lancet Infect Dis. 2009 Apr;9(4):219-27. doi: 10.1016/S1473-3099(09)70071-4.

  PMID: 19324294 BACKGROUND

• McCollum ED, Bjornstad E, Preidis GA, Hosseinipour MC, Lufesi N. Multicenter study of hypoxemia prevalence and quality of oxygen treatment for hospitalized Malawian children. Trans R Soc Trop Med Hyg. 2013 May;107(5):285-92. doi: 10.1093/trstmh/trt017.

  PMID: 23584373 BACKGROUND

• McCollum ED, King C, Hammitt LL, Ginsburg AS, Colbourn T, Baqui AH, O'Brien KL. Reduction of childhood pneumonia mortality in the Sustainable Development era. Lancet Respir Med. 2016 Dec;4(12):932-933. doi: 10.1016/S2213-2600(16)30371-X. Epub 2016 Nov 12. No abstract available.

  PMID: 27843130 BACKGROUND

• Lazzerini M, Sonego M, Pellegrin MC. Hypoxaemia as a Mortality Risk Factor in Acute Lower Respiratory Infections in Children in Low and Middle-Income Countries: Systematic Review and Meta-Analysis. PLoS One. 2015 Sep 15;10(9):e0136166. doi: 10.1371/journal.pone.0136166. eCollection 2015.

  PMID: 26372640 BACKGROUND

• Walsh BK, Smallwood CD. Pediatric Oxygen Therapy: A Review and Update. Respir Care. 2017 Jun;62(6):645-661. doi: 10.4187/respcare.05245.

  PMID: 28546370 BACKGROUND

• Sonego M, Pellegrin MC, Becker G, Lazzerini M. Risk factors for mortality from acute lower respiratory infections (ALRI) in children under five years of age in low and middle-income countries: a systematic review and meta-analysis of observational studies. PLoS One. 2015 Jan 30;10(1):e0116380. doi: 10.1371/journal.pone.0116380. eCollection 2015.

  PMID: 25635911 BACKGROUND

• Liu L, Oza S, Hogan D, Chu Y, Perin J, Zhu J, Lawn JE, Cousens S, Mathers C, Black RE. Global, regional, and national causes of under-5 mortality in 2000-15: an updated systematic analysis with implications for the Sustainable Development Goals. Lancet. 2016 Dec 17;388(10063):3027-3035. doi: 10.1016/S0140-6736(16)31593-8. Epub 2016 Nov 11.

  PMID: 27839855 BACKGROUND

MeSH Terms

Conditions

Pneumonia

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Eric E McCollom, MD, MPH

  Johns Hopkins School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Pilot trial to assess feasibility of the protocol for a three-armed, open-label randomized controlled trial

Study Record Dates

• First Submitted: December 6, 2023
• First Posted: December 20, 2023
• Study Start: May 15, 2024
• Primary Completion: November 30, 2024
• Study Completion: November 30, 2024
• Last Updated: December 20, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, ANALYTIC CODE
• Time Frame: Data will be provided at the time of the primary outcome publication(s) for a period of at least 10 years.
• 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

Locations

MA (1)