Controlled evaLuation of Angiotensin Receptor Blockers for COVID-19 respIraTorY Disease (CLARITY)



Angiotensin Receptor Blockers (ARBs) inhibit the Angiotensin II Type 1 Receptor (AT1R). In the non-COVID-19 setting, AT1R promotes constriction of blood vessels, inflammation and tissue scaring. At a microscopic level it facilitates the entry into cells of a protein called ACE2. ACE2 is used by SARS-CoV-2, the virus responsible for COVID-19, to gain entry into host cells and is found on cells in the lung, heart and kidney, among others, reflecting the clinical manifestations of severe COVID-19.

ARBs may ameliorate the effects of SARS-CoV-2 infection by three mechanisms:

  1. inhibiting AT1R-dependent internalisation of ACE2, interrupting viral cellular entry,
  2. reducing AT1R-dependent cleavage of ACE2, thereby restoring anti-inflammatory ACE2 activity, and
  3. blocking pro-inflammatory responses of the ACE-ANG II-AT1R pathway, reducing inflammation, fibrosis & lung injury.


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 + Placebo

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 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. 



CLARITY aims to establish whether ARBs can shorten the duration of severe COVID-19 disease and reduce the risk of severe disease.

Supported By:

Australian Medical Research Future Fund (MRFF) 2020 Respiratory Medicine Clinical Trials Research on COVID-19 Grant and The University of Sydney


Potential participants must satisfy all of the following:

  1. Laboratory-confirmed diagnosis of SARS-CoV-2 infection within 10 days prior to randomisation
  2. Age ≥ 18 years
  3. a) Systolic Blood Pressure (SBP) ≥ 120 mmHg OR b) SBP ≥ 115 mmHg and currently treated with a non-RAASi Blood Pressure (BP) lowering agent that can be ceased
  4. Participant and treating clinician are willing and able to perform trial procedures.
  5. a) Intended for hospital admission for management of COVID-19, OR b) (In Australia Only) Intended for management at home with one or more of the following criteria:
    1. Age≥60 years
    2. BMI ≥30kg/m2 (derived from the patient’s self-report of their height and weight where these are not measured directly)
    3. Diagnosis of diabetes defined as HbA1c ≥7% and/or the consumption of glucose lowering medication
    4. History of cardiovascular disease
    5. History of chronic respiratory illness
    6. Currently treated with immunosuppression

Registration ID:



International (Australia & India)

Australian Lead Group:

NHMRC CTC, The University of Sydney & The George Institute for Global Health



Activation Date:



Professor Meg Jardine



Main publication

Protocol publication

Statistical Analysis Plan publication

American Society of Nephrology (ASN) 2022 Late Breaking Poster