Statistical Analysis Plan for the Helmet Non-Invasive Ventilation for COVID-19 Patients (Helmet-COVID) Randomized Controlled Trial

Background and objectiveNoninvasive respiratory support is frequently needed for patients with acute hypoxemic respiratory failure due to coronavirus disease 19 (COVID-19). Helmet noninvasive ventilation having multiple advantages over other support modalities but data about effectiveness are limited. MethodsIn this multicenter randomized trial of helmet non-invasive ventilation for COVID-19 patients (Helmet-COVID), 320 adult ICU patients with suspected or confirmed COVID-19 and acute hypoxemic respiratory failure (with a ratio of arterial oxygen partial pressure to fraction (percent) of inspired oxygen (PaO2/FiO2) 10 L/min or above) will be randomized to helmet-noninvasive ventilation with usual care or usual care alone. The primary outcome is death from any cause within 28 days after randomization. The trial has 80% power to detect a 15% absolute risk reduction from 40% to 25%. ConclusionConsistent with international guidelines, we developed a detailed plan to guide the analysis of the Helmet-COVID trial. This plan specifies the statistical methods for the evaluation of primary and secondary outcomes to facilitate unbiased analyses of clinical data. Trial registrationClinicaltrials.gov: NCT04477668 (registered on July 20, 2020)