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

The George Institute

Status and phase: Completed; Phase 4

Conditions: COVID-19; Coronavirus Disease 2019

Treatments: Other: Placebo; Drug: Angiotensin Receptor Blockers

Study type: Interventional

Funder types: Other

Identifiers

NCT04394117

11052020

Details and patient eligibility

About

The Controlled evaLuation of Angiotensin Receptor Blockers for COVID-19 respIraTorY disease (CLARITY) study is a pragmatic prospective, open-label, randomised controlled trial. CLARITY aims to examine the effectiveness of angiotensin II receptor blockers (ARBs) on improving the outcomes of people who tested positive for COVID-19 disease.

Enrollment: 787 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

Potential participants must satisfy all of the following:

1. Laboratory-confirmed* diagnosis of Severe Acute Respiratory Syndrome-Coronavirus-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-Renin Angiotensin Aldosterone System inhibitor Blood Pressure (BP) lowering agent that can be ceased

4. Participant and treating clinician are willing and able to perform trial procedures.

5. Either Intended for hospital admission for management of COVID-19, or (In Australia Only) Intended for management at home with one or more of the following criteria:

   1. Age≥60 years
   2. Body Mass Index ≥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

Exclusion criteria

1. Currently treated with an angiotensin-converting enzyme inhibitor, Angiotensin Receptor Blocker or aldosterone antagonist, aliskiren, or angiotensin receptor-neprilysin inhibitors (ARNi)

2. Serum potassium > 5.2 mmol/L or no potassium testing within the last 3 months

3. For those intended for hospital admission, an estimated Glomerular Filtration Rate (eGFR) <30ml/min/1.73m2 or no eGFR testing within the last 3 months, or For those intended for management at home (Australia only), an eGFR <45ml/min/1.73m2 or no eGFR testing within the last 3 months

4. Known symptomatic postural hypotension

5. Known biliary obstruction, known severe hepatic impairment (Child-Pugh-Turcotte score 10-15) - see Table below

6. Intolerance of ARB

7. Pregnancy or risk of pregnancy, defined as;

   1. (In Australia only) Women younger than 51 years who have not had a negative pregnancy test during the past 3 days and/or who do not agree to use adequate contraception
   2. (In India Only) Women who are pregnant

8. Women who are currently breastfeeding

9. Individuals who are not able to take medications by mouth at enrolment, or who are not expected to be able to take medications by mouth during the first 48 hours after randomisation

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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787 participants in 2 patient groups, including a placebo group

Standard Care + Angiotensin Receptor Blocker (ARB)

Active Comparator group

Description:

Participants will receive an Angiotensin Receptor Blocker on top of the standard care provided by their institution.

Treatment:

Drug: Angiotensin Receptor Blockers

Standard Care + Placebo

Placebo Comparator group

Description:

Participants will receive a placebo on top of the standard care provided by their institution.

Treatment:

Other: Placebo