Controlled evaLuation of Angiotensin Receptor Blockers for COVID-19 respIraTorY disease (CLARITY): Statistical analysis plan for a randomised controlled Bayesian adaptive sample size trial (preprint)

ABSTRACT

The CLARITY trial (Controlled evaLuation of Angiotensin Receptor Blockers for COVID-19 respIraTorY Disease) investigates the effectiveness of angiotensin receptor blockers in addition to standard care compared to placebo (in Indian sites) with standard care in reducing the duration and severity of lung failure in patients with COVID-19. The CLARITY trial is a multi-centre, randomised controlled Bayesian adaptive trial with regular planned analyses where pre-specified decision rules will be assessed to determine whether the trial should be stopped due to sufficient evidence of treatment effectiveness or futility. Here we describe the statistical analysis plan for the trial, and define the pre-specified decision rules, including those that could lead to the trial being halted. The primary outcome is clinical status on a 7-point ordinal scale adapted from the WHO Clinical Progression scale assessed at Day 14. The primary analysis will follow the intention-to-treat principle. A Bayesian adaptive trial design was selected because there is considerable uncertainty about the extent of potential benefit of this treatment. Trial registrationClinicalTrials.gov, NCT04394117. Registered on 19 May 2020. https//clinicaltrials.gov/ct2/show/NCT04394117 Clinical Trial Registry of India CTRI/2020/07/026831 Version and revisionsVersion 1.0. No revisions.