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

Arabi, Y.; Tlayjeh, H.; Aldekhyl, S.; Al-Dorzi, H.; Abdukahil, S.; Jose, J.; Al Harbi, M. K.; Al Haji, H.; Al Mutairi, M.; Al Zumai, O.; Al Qasim, E.; Al Wehaibi, W.; Al Qahtani, S.; Alshahrani, M.; Albrahim, T.; Mady, A.; Bshabshe, A.; Al Aseri, Z.; Al Duhailib, Z.; Kharaba, A.; Alqahtani, R.; Algethamy, H.; Alfaris, O.; Alnafel, O.; Al-Fares, A.

Background and objective Noninvasive 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. Methods In 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) <200 despite supplemental oxygen with a partial/non-rebreathing mask at a flow rate >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%. Conclusion Consistent 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.