High flow oxygen compared to standard flow oxygen for hospitalized adults with acute hypoxemia in Africa (BREATHE): a protocol for a multinational Type 1 implementation-effectiveness randomized controlled trial

Acute hypoxemic respiratory failure is common and associated with high mortality, particularly in resource-constrained settings. High flow oxygen is a form of advanced non-invasive respiratory support that has been demonstrated to reduce the need for invasive mechanical ventilation (moderate certainty) and reduce mortality (low certainty) in adults with acute hypoxemic respiratory failure in resource-rich settings. High flow oxygen has the potential to provide even greater benefit in resource-constrained settings where safe mechanical ventilation is less available, though also has the potential for increased risk in these settings. BREATHE is a multinational Type 1 implementation-effectiveness randomized controlled trial, with a primary objective to determine whether protocolized high flow oxygen will change in-hospital mortality as compared with protocolized standard flow oxygen. We will complete a randomized controlled trial of 1600 adults with acute hypoxemia in five hospitals in Kenya, Malawi, and Rwanda with two arms: protocolized high flow oxygen and protocolized standard flow oxygen. Adults admitted to these hospitals are screened within 24 hours of admission. Patients who are eligible and consent are randomized to either high flow or standard flow oxygen throughout their hospitalizations. All participants receive protocolized oxygen therapy: monitoring with pulse oximetry at prescribed intervals, titration to peripheral oxygen saturation range of 90–94%, and liberation from oxygen therapy per a de-escalation protocol. Qualitative data from research staff, clinical staff, and patients and families is collected and analyzed, to assess contextual factors influencing implementation. The primary outcome is in-hospital mortality. Secondary outcomes include 90-day mortality; 90-day functional status; 90-day readmission; hospital care outcomes; escalation to ventilation; oxygen consumption; and implementation factors. We will also compare outcomes for trial participants with outcomes for participants in a baseline audit who received usual oxygen therapy at these hospitals prior to the trial. ,