Controlled evaLuation of Angiotensin Receptor Blockers for COVID-19 respIraTorY Disease (CLARITY)
Background:
Angiotensin Receptor Blockers (ARBs) inhibit the Angiotensin II Type 1 Receptor (AT1R). In the non-COVID-19 setting, AT1R promotes vasoconstriction, inflammation and fibrosis, and facilitates endocytosis and cleavage of extracellular membrane-bound ACE2. ACE2 is used by SARS-CoV-2, the virus responsible for COVID-19, to gain entry into host cells and is expressed on type 2 alveolar lung cells, cardiomyocytes and renal tubular cells, among others, reflecting the clinical manifestations of severe COVID-19.
ARBs may ameliorate the effects of SARS-CoV-2 infection by two mechanisms:
- inhibiting AT1R-dependent internalisation of ACE2, interrupting viral cellular entry
- reducing AT1R-dependent cleavage of ACE2, thereby restoring anti-inflammatory ACE2 activity.
Aim:
CLARITY aims to establish whether ARBs can shorten the duration of severe COVID-19 disease and reduce the risk of severe disease.
Research Methodology:
The CLARITY trial is an investigator-initiated, multicentre, international, prospective, randomised controlled trial.
Participants will be randomised to either:
- Experimental intervention: Standard Care + Angiotensin Receptor Blocker
- Control: Standard Care
CLARITY has been designed to be delivered through existing health service processes with minimal additional impact on the delivery of clinical care. Recruitment of participants into CLARITY will continue until prespecified statistical rules are met. Participants will be recruited from a number of countries, not limited to, Australia and India.
CLARITY will convene and partner with a consumer and community engagement group to deliver the trial. The group will provide input into the development of the trial and all patient facing aspects of the trial, including advertising, recruitment, consent, trial delivery & results dissemination.
Current Status:
The trial is active and recruiting since Quarter 3 2020.
Australian Medical Research Future Fund (MRFF) 2020 Respiratory Medicine Clinical Trials Research on COVID-19 Grant has provided funding for the trial.
