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

Phase 4

Completed

• Conditions: COVID-19; Coronavirus Disease 2019
• Interventions: Drug: Angiotensin Receptor Blockers; Other: Placebo

• Registration Number: NCT04394117
• Lead Sponsor: The George Institute

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-05-18
• Study First Submitted QC: 2020-05-18
• Study First Posted: 2020-05-19
• Study Start: 2020-06-19
• Primary Completion: 2021-11-14
• Study Completion: 2022-01-17
• Status Verified: 2022-03
• Last Update Submitted: 2022-03-02
• Last Update Posted: 2022-03-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 787

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Standard Care + Angiotensin Receptor Blocker (ARB)	Angiotensin Receptor Blockers	Participants will receive an Angiotensin Receptor Blocker on top of the standard care provided by their institution.
Standard Care + Placebo	Placebo	Participants will receive a placebo on top of the standard care provided by their institution.

Primary Outcome Measures

Name	Time	Method
7-Point National Institute of Health Clinical Health Score	14 Days	To determine whether the addition of the intervention, compared to standard care, changes the clinical health score of a participant on the following scale; 1. Not hospitalized, no limitations on activities.; 2. Not hospitalized, limitation on activities; 3. Hospitalized, not requiring supplemental oxygen; 4. Hospitalized, requiring supplemental oxygen; 5. Hospitalized, on non-invasive ventilation or high flow oxygen devices; 6. Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 7. Death;

Secondary Outcome Measures

Name	Time	Method
Hospitalisation Days	90 Days	To determine whether the addition of the intervention, compared to standard care, changes the number of hospitalisation days
Dialysis Requirement	28 Days	To determine whether the addition of the intervention, compared to standard care, changes the requirements for dialysis
Ventilator-Free Days	28 Days	To determine whether the addition of the intervention, compared to standard care, changes need for ventilation
Mortality	90 Days	To determine whether the addition of the intervention, compared to standard care, changes the risk of all cause mortality
Acute Kidney Injury	28 Days	To determine whether the addition of the intervention, compared to standard care, changes risk of acute kidney injury, based on the Kidney Disease: Improving Global Outcomes definition
Dialysis Days	28 Days	To determine whether the addition of the intervention, compared to standard care, changes need for dialysis
Hypotension Requiring Vasopressors	28 Days	To determine whether the addition of the intervention, compared to standard care, changes risk of hypotension requiring vasopressors
7-Point National Institute of Health Clinical Health Score	28 Days	To determine whether the addition of the intervention, compared to standard care, changes the clinical health score of a participant on the following scale; 1. Not hospitalized, no limitations on activities.; 2. Not hospitalized, limitation on activities; 3. Hospitalized, not requiring supplemental oxygen; 4. Hospitalized, requiring supplemental oxygen; 5. Hospitalized, on non-invasive ventilation or high flow oxygen devices; 6. Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 7. Death;
Intensive Care Unit Admission	90 Days	To determine whether the addition of the intervention, compared to standard care, changes the count of all cause Intensive Care Unit admission
Respiratory Failure	28 Days	To determine whether the addition of the intervention, compared to standard care, changes the incidence of respiratory failure
Intensive Care Unit Number of Days	90 Days	To determine whether the addition of the intervention, compared to standard care, changes the number of days total, of intensive care unit admission

Trial Locations

Locations (22)

Western Health; 🇦🇺 St Albans, Victoria, Australia

Christian Hospital; 🇮🇳 Nabarangpur, India

Alfred Health; 🇦🇺 Melbourne, Victoria, Australia

All India Institute of Medical Science; 🇮🇳 Raipur, India

Post Graduate Institute of Medical Education & Research; 🇮🇳 Chandigarh, India

Lok Nayak Jai Prakash; 🇮🇳 Delhi, India

Kasturba Medical College; 🇮🇳 Manipal, India

Jivenrekha Hospital; 🇮🇳 Pune, India

Austin Health; 🇦🇺 Heidelberg, Victoria, Australia

Royal North Shore Hospital; 🇦🇺 St Leonards, New South Wales, Australia

Canterbury Hospital; 🇦🇺 Campsie, New South Wales, Australia

Royal Prince Alfred Hospital; 🇦🇺 Camperdown, 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

Westmead Hospital; 🇦🇺 Westmead, New South Wales, Australia

Wollongong Hospital; 🇦🇺 Wollongong, New South Wales, Australia

Northern Health; 🇦🇺 Epping, Victoria, Australia

Government Medical College & Hospital; 🇮🇳 Chandigarh, India