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.
Drug: Angiotensin Receptor Blockers
Angiotensin Receptor Blockers (ARBs) have been in clinical use for more than 30 years for their cardiac and renal protective effects. ARBs mechanism of action is through selective inhibition of angiotensin-II (Ang-II) by competitive antagonism of the angiotensin receptor. ARBs displace ang-II from the angiotensin I receptor and produce their protective effects by reducing the downstream effects of ang-II induced vasoconstriction, aldosterone release, catecholamine release, arginine vasopressin release, water intake, and hypertrophic response The virus causing COVID-19, SARS-CoV-2, binds to the extracellular portion of Angiotensin-Converting-Enzyme-2 (ACE2) expressed on type II alveolar cells in the lungs which is followed by internalization of ACE2 before downregulating membrane ACE2 expression. Both these components appear to require angiotensin receptor Type 1 (AT1R), and ARBs, which block the actions of AT1R, would reduce the severity of COVID-19 and reduce the duration of symptoms
Other Name: Array
Other: Placebo
Placebo
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
Royal Prince Alfred Hospital
Camperdown, New South Wales, Australia
Canterbury Hospital
Campsie, New South Wales, Australia
The Sutherland Hospital
Caringbah, New South Wales, Australia
Concord Hospital
Concord, New South Wales, Australia
St George Hospital
Kogarah, New South Wales, Australia
Liverpool Hospital
Liverpool, New South Wales, Australia
John Hunter Hospital
New Lambton Heights, New South Wales, Australia
Prince of Wales Hospital
Randwick, New South Wales, Australia
Royal North Shore Hospital
St Leonards, New South Wales, Australia
Westmead Hospital
Westmead, New South Wales, Australia
Wollongong Hospital
Wollongong, New South Wales, Australia
Northern Health
Epping, Victoria, Australia
Austin Health
Heidelberg, Victoria, Australia
Alfred Health
Melbourne, Victoria, Australia
Western Health
St Albans, Victoria, Australia
Government Medical College & Hospital
Chandigarh, India
Post Graduate Institute of Medical Education & Research
Chandigarh, India
Lok Nayak Jai Prakash
Delhi, India
Kasturba Medical College
Manipal, India
Christian Hospital
Nabarangpur, India
Jivenrekha Hospital
Pune, India
All India Institute of Medical Science
Raipur, India
Meg Jardine, Study Chair
University of Sydney