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

COVID-19 Clinical Trial

— CLARITY  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04394117
• Other study ID #: 11052020
• Status: Completed
• Phase: Phase 4
• Start date: June 19, 2020
• Est. completion date: January 17, 2022

Study information

• Verified date: March 2022
• Source: The George Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 787
• Est. completion date: January 17, 2022
• Est. primary completion date: November 14, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Coronavirus Disease 2019
• Coronavirus Infections
• COVID-19
• Respiration Disorders
• Respiratory Tract Diseases

Intervention

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:
• Placebo
Placebo

Locations

Country	Name	City	State
Australia	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	Northern Health	Epping	Victoria
Australia	Austin Health	Heidelberg	Victoria
Australia	St George Hospital	Kogarah	New South Wales
Australia	Liverpool Hospital	Liverpool	New South Wales
Australia	Alfred Health	Melbourne	Victoria
Australia	John Hunter Hospital	New Lambton Heights	New South Wales
Australia	Prince of Wales Hospital	Randwick	New South Wales
Australia	Western Health	St Albans	Victoria
Australia	Royal North Shore Hospital	St Leonards	New South Wales
Australia	Westmead Hospital	Westmead	New South Wales
Australia	Wollongong Hospital	Wollongong	New South Wales
India	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

Sponsors (1)

Lead Sponsor	Collaborator
The George Institute

Countries where clinical trial is conducted

Australia,  India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Hyperkalaemia	To determine whether the addition of the intervention, compared to standard care, changes risk of hyperkalaemia.	Day 28
Other	Oxygen Saturation	To determine whether the addition of the intervention, compared to standard care, changes risk of decreased oxygen saturation	Day 28
Other	Oxygen Saturation	To determine whether the addition of the intervention, compared to standard care, changes risk of decreased oxygen saturation	Day 14
Primary	7-Point National Institute of Health Clinical Health Score	To determine whether the addition of the intervention, compared to standard care, changes the clinical health score of a participant on the following scale; Not hospitalized, no limitations on activities.; Not hospitalized, limitation on activities; Hospitalized, not requiring supplemental oxygen; Hospitalized, requiring supplemental oxygen; Hospitalized, on non-invasive ventilation or high flow oxygen devices; Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); Death;	14 Days
Secondary	7-Point National Institute of Health Clinical Health Score	To determine whether the addition of the intervention, compared to standard care, changes the clinical health score of a participant on the following scale; Not hospitalized, no limitations on activities.; Not hospitalized, limitation on activities; Hospitalized, not requiring supplemental oxygen; Hospitalized, requiring supplemental oxygen; Hospitalized, on non-invasive ventilation or high flow oxygen devices; Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); Death;	28 Days
Secondary	Mortality	To determine whether the addition of the intervention, compared to standard care, changes the risk of all cause mortality	28 Days
Secondary	Mortality	To determine whether the addition of the intervention, compared to standard care, changes the risk of all cause mortality	90 Days
Secondary	Intensive Care Unit Admission	To determine whether the addition of the intervention, compared to standard care, changes the count of all cause Intensive Care Unit admission	28 Days
Secondary	Intensive Care Unit Admission	To determine whether the addition of the intervention, compared to standard care, changes the count of all cause Intensive Care Unit admission	90 Days
Secondary	Intensive Care Unit Number of Days	To determine whether the addition of the intervention, compared to standard care, changes the number of days total, of intensive care unit admission	90 Days
Secondary	Respiratory Failure	To determine whether the addition of the intervention, compared to standard care, changes the incidence of respiratory failure	28 Days
Secondary	Dialysis Requirement	To determine whether the addition of the intervention, compared to standard care, changes the requirements for dialysis	28 Days
Secondary	Hospitalisation Days	To determine whether the addition of the intervention, compared to standard care, changes the number of hospitalisation days	28 Days
Secondary	Hospitalisation Days	To determine whether the addition of the intervention, compared to standard care, changes the number of hospitalisation days	90 Days
Secondary	Ventilator-Free Days	To determine whether the addition of the intervention, compared to standard care, changes need for ventilation	28 Days
Secondary	Dialysis Days	To determine whether the addition of the intervention, compared to standard care, changes need for dialysis	28 Days
Secondary	Acute Kidney Injury	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	28 Days
Secondary	Hypotension Requiring Vasopressors	To determine whether the addition of the intervention, compared to standard care, changes risk of hypotension requiring vasopressors	28 Days