Helmet noninvasive ventilation for COVID-19 patients (Helmet-COVID): statistical analysis plan for a randomized controlled trial.

BACKGROUND: Noninvasive respiratory support is frequently needed for patients with acute hypoxemic respiratory failure due to coronavirus disease 19 (COVID-19). Helmet noninvasive ventilation has multiple advantages over other oxygen support modalities but data about effectiveness are limited. METHODS: In this multicenter randomized trial of helmet noninvasive ventilation for COVID-19 patients, 320 adult ICU patients (aged ≥14 years or as per local standards) with suspected or confirmed COVID-19 and acute hypoxemic respiratory failure (ratio of arterial oxygen partial pressure to fraction of inspired oxygen < 200 despite supplemental oxygen with a partial/non-rebreathing mask at a flow rate of 10 L/min or higher) will be randomized to helmet noninvasive ventilation with usual care or usual care alone, which may include mask noninvasive ventilation, high-flow nasal oxygen, or standard oxygen therapy. 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 in 28-day mortality from 40 to 25%. The primary outcome will be compared between the helmet and usual care group in the intention-to-treat using the chi-square test. Results will be reported as relative risk  and 95% confidence interval. The first patient was enrolled on February 8, 2021. As of August 1, 2021, 252 patients have been enrolled from 7 centers in Saudi Arabia and Kuwait. DISCUSSION: We developed a detailed statistical analysis plan to guide the analysis of the Helmet-COVID trial, which is expected to conclude enrollment in November 2021. TRIAL REGISTRATION: ClinicalTrials.gov NCT04477668 . Registered on July 20, 2020.

Helmet Non-Invasive Ventilation for COVID-19 Patients (Helmet-COVID): study protocol for a multicentre randomised controlled trial.

INTRODUCTION: Non-invasive ventilation (NIV) delivered by helmet has been used for respiratory support of patients with acute hypoxaemic respiratory failure due to COVID-19 pneumonia. The aim of this study was to compare helmet NIV with usual care versus usual care alone to reduce mortality. METHODS AND ANALYSIS: This is a multicentre, pragmatic, parallel randomised controlled trial that compares helmet NIV with usual care to usual care alone in a 1:1 ratio. A total of 320 patients will be enrolled in this study. The primary outcome is 28-day all-cause mortality. The primary outcome will be compared between the two study groups in the intention-to-treat and per-protocol cohorts. An interim analysis will be conducted for both safety and effectiveness. ETHICS AND DISSEMINATION: Approvals are obtained from the institutional review boards of each participating institution. Our findings will be published in peer-reviewed journals and presented at relevant conferences and meetings. TRIAL REGISTRATION NUMBER: NCT04477668.