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. 2022 Jan 10;38(3):601–621. doi: 10.1016/j.ccc.2022.01.006

Table 2.

Randomized controlled trials (recruiting or nonrecruiting) evaluating noninvasive respiratory support (high-flow nasal oxygen or noninvasive ventilation) in patients with COVID-19 and acute hypoxemic respiratory failure

Trial Identifier/Status Country Design Population Sample Size Intervention Primary Outcome
Comparison of HFNO, face-mask NIV and helmet NIV in COVID-19 ARDS patients (NIV COVID-19) ClinicalTrials.gov Identifier: NCT04715243
Recruiting
Oman Multicenter RCT Patients with confirmed COVID-19 in the emergency department, the ward, high dependency, or ICU with ARDS requiring NIV 360 Patients assigned to 1 of 3 arms: HFNO, face-mask NIV, or helmet NIV Rate of endotracheal intubation
Helmet noninvasive ventilation for COVID-19 patients (Helmet-COVID) ClinicalTrials.gov Identifier: NCT04477668
Recruiting
Saudi Arabia Multicenter RCT COVID-19 with AHRF 320 Pragmatic parallel RCT that will compare helmet NIV with standard of care to standard of care alone in 1:1 ratio. The trial will be implemented in multiple centers 28-d all-cause mortality
Early CPAP in COVID-19 patients with respiratory failure (EC-COVID-RCT) ClinicalTrials.gov Identifier: NCT04326075 Italy Single-center RCT Patients in the emergency department with confirmed or suspected COVID-19 and Spo2 < 95% with PF ratio > 200 900 Early helmet CPAP vs usual care Death or need of intubation
High-flow nasal oxygen vs CPAP helmet in COVID-19 pneumonia (COVIDNOCHE) ClinicalTrials.gov Identifier: NCT04381923
Not recruiting (by August 26, 2021)
USA Single-center RCT Patients with COVID-19 and refractory hypoxemia (Spo2 ≤ 92% on O2 ≥ 6 L/min by nasal cannula) 200 Advanced respiratory units will be assigned to use 1 of 2 default interventions (helmet CPAP vs HFNO) as the first-line treatment Ventilator-free days within 28 d
High-flow nasal therapy vs conventional oxygen therapy in COVID-19 (COVID-HIGH) ClinicalTrials.gov Identifier: NCT04655638
Recruiting
Italy Multicenter RCT (Europe) Patients with confirmed COVID-19–related AHRF in any hospital ward caring for COVID-19 patients 364 HFNO vs conventional oxygen therapy Proportion of patients needing escalation of treatment (ie, NIV, including CPAP, or intubation) by 28 d

The search was performed on August 26, 2021, in ClinicalTrials.gov, using the following terms: adults (≥18 y), COVID, interventional studies, all countries, recruiting or nonrecruiting, and each of the following: noninvasive ventilation (yielded 167 studies) OR high-flow nasal oxygen (yielded 26 studies) OR continuous positive airway pressure (yielded 15 studies). Only 5 studies were RCTs as reported. Additional search on September 15, 2021, in International Clinical Trials Registry Platform and ISRCTN registry, did not yield any additional studies.