Building Respiratory Support in East Africa Through High Flow Versus Standard Flow Oxygen Evaluation (BREATHE)

Acute hypoxemia is common and deadly in resource variable settings. While studies in high income countries (HICs) have indicated a possible benefit to high flow oxygen as compared with standard flow oxygen, rigorous studies in low or lower middle income countries (LMICs) have not been performed. Studies in sepsis have demonstrated that interventions that improve outcomes in one context may actually be neutral or harmful in a different context.

The goal of this study is to test whether high flow oxygen results in better outcomes for hypoxemic adult patients, as compared with standard flow oxygen, in five LMIC hospitals. The main questions it aims to answer are:

1. For hypoxemic adults in these LMIC study settings, does high flow oxygen or standard flow oxygen result in lower mortality?
2. What are the facilitators and barriers to using high flow oxygen in these settings?
3. Does high flow or standard flow oxygen use more oxygen?

Participants will be randomized to receive either high flow oxygen through a large nasal cannula, or to receive standard flow oxygen, through nasal cannulas, face masks, or non-rebreather masks. Researchers will compare the outcomes for the two groups, to see if one group of patients has better outcomes than the other.

The study will also examine how much oxygen is used by the two patient groups, as well as other factors relevant to the feasibility of implementation of high flow oxygen in these sites.

Study Overview

• Status: Recruiting
• Conditions: Acute Hypoxemia
• Intervention / Treatment: Device: High flow oxygen; Other: Standard flow oxygen

• Study Type: Interventional
• Enrollment (Estimated): 1054
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Elisabeth Riviello, MD, MPH; Phone Number: +1 617 447 5131; Email: eriviell@bidmc.harvard.edu
• Study Contact Backup: Name: Theogene Twagirumugabe, MD, PhD; Phone Number: +250 788 539 904; Email: twagirumugabe@gmail.com

Study Locations

• Kenya
  • Kijabe, Kenya
    • Recruiting
    • AIC Kijabe Hospital
    • Contact: Nelly Kebeny, RN
    • Principal Investigator: George Otieno, MBChB, MMed
  • Nakuru, Kenya
    • Recruiting
    • Nakuru Level V Hospital
    • Contact: Wanja Kageche, RN
    • Principal Investigator: Peter Oduor, MBChB, MMed
• Malawi
  • Blantyre, Malawi
    • Recruiting
    • Queen Elizabeth Central Hospital
    • Contact: Innocent Sulani, MBBS, MSc
    • Principal Investigator: Stephen Gordon, MD
• Rwanda
  • Huye, Rwanda
    • Recruiting
    • The University Teaching Hospital of Butare (CHUB)
    • Contact: Blaise Gahungu, MMed
    • Principal Investigator: Theogene Twagirumugabe, MMed,MD,PhD
  • Kigali, Rwanda
    • Recruiting
    • The University Teaching Hospital of Kigali (CHUK)
    • Contact: Dona Fabiola, MMed
    • Principal Investigator: Doris Uwamahoro, MMed

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• age>=18 years AND
• admitted to a study site hospital within the 24 hours prior to screening AND
• SpO2<90% at time of first assessment OR
• receiving oxygen at time of first assessment

Exclusion Criteria:

• imminent death (high clinical suspicion of death within 24 hours of admission)
• patient or caregiver refusal of study participation
• history of chronic respiratory failure (SpO2<90% or oxygen dependence for at least three months)
• anatomical factors precluding the use of nasal cannula
• intubation or non-invasive ventilation by the clinical team prior to screening for the trial
• known hypoxemia at transferring facility for >48 hours
• lack of availability of either SFO or HFO devices or supplies at the time of randomization.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High flow oxygen; Heated and humidified oxygen delivered via high flow oxygen device through nasal cannula, up to 60 liters per minute of flow.	Device: High flow oxygen; humidified and heated oxygen delivered at high flow rates via nasal cannula, with protocol to target SpO2 90-94%
Active Comparator: Standard flow oxygen; Oxygen delivered via standard oxygen devices at standard flows up to 15 liters per minute: nasal cannula, face mask, or nonrebreather mask.	Other: Standard flow oxygen; oxygen delivered at standard flow rates via nasal cannula, facemask, or nonrebreather mask, with protocol to target SpO2 90-94%

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
In-hospital mortality	Death between randomization and end of hospitalization	Day 90

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
90-day mortality	Death between randomization and 90 days	Day 90
90-day functional status	Functional status 90 days after randomization, as measured by the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0)	Day 90
Need for mechanical ventilation	Met objective criteria for need to escalate respiratory therapy to NIV or invasive ventilation, or escalated to NIV or mechanical ventilation	Day 90
Days requiring oxygen	Days requiring oxygen from randomization to end of hospitalization	Day 90
Hospital length of stay	Days from randomization to hospital discharge or death	Day 90
ICU length of stay	Total days in the ICU during hospitalization	Day 90
Time to meeting criteria for need for escalation to either NIV or invasive ventilation	Time to meeting objective clinical criteria for escalation to non-invasive ventilation or invasive ventilation	Day 90
Time to escalation to either NIV or invasive ventilation	Time to escalation to non-invasive ventilation or invasive ventilation	Day 90

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Oxygen consumption	Total oxygen consumed during hospitalization	Day 90

Collaborators and Investigators

• Sponsor: Beth Israel Deaconess Medical Center
• Collaborators: Wellcome
• Investigators: Principal Investigator: Elisabeth Riviello, MD, MPH, Beth Israel Deaconess Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): October 11, 2023
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): March 31, 2025

Study Registration Dates

• First Submitted: February 7, 2023
• First Submitted That Met QC Criteria: February 21, 2023
• First Posted (Actual): March 3, 2023

Study Record Updates

• Last Update Posted (Actual): March 13, 2024
• Last Update Submitted That Met QC Criteria: March 12, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Signs and Symptoms, Respiratory; Hypoxia
• Other Study ID Numbers: 2022P001102; 222165/Z/20/Z (Other Grant/Funding Number: Wellcome Trust (WT))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: IPD will not be shared with other researchers for the trial overall. IPD is owned and managed by each of the sites for the trial, in accordance with the data protection requirements of each country where the sites are located. Individual sites may decide to share their own IPD with other researchers.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No