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Completed

NCT Number: NCT04394117

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

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.

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Key information

Conditions

Coronavirus Disease 2019 COVID-19 Coronaviridae Infections Coronavirus Infections Infections Lung Diseases Nidovirales Infections Pneumonia Pneumonia, Viral RNA Virus Infections Respiratory Tract Diseases Respiratory Tract Infections Virus Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

Potential participants must satisfy all of the following:

  • Laboratory-confirmed* diagnosis of Severe Acute Respiratory Syndrome-Coronavirus-2 infection within 10 days prior to randomisation
  • Age ≥ 18 years
  • 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
  • Participant and treating clinician are willing and able to perform trial procedures.
  • 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:
  • Age≥60 years
  • Body Mass Index ≥30kg/m2 (derived from the patient's self-report of their height and weight where these are not measured directly)
  • Diagnosis of diabetes defined as HbA1c ≥7% and/or the consumption of glucose lowering medication
  • History of cardiovascular disease
  • History of chronic respiratory illness
  • Currently treated with immunosuppression

Exclusion criteria

  • Currently treated with an angiotensin-converting enzyme inhibitor, Angiotensin Receptor Blocker or aldosterone antagonist, aliskiren, or angiotensin receptor-neprilysin inhibitors (ARNi)
  • Serum potassium > 5.2 mmol/L or no potassium testing within the last 3 months
  • 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
  • Known symptomatic postural hypotension
  • Known biliary obstruction, known severe hepatic impairment (Child-Pugh-Turcotte score 10-15) - see Table below
  • Intolerance of ARB
  • Pregnancy or risk of pregnancy, defined as;
  • (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
  • (In India Only) Women who are pregnant
  • Women who are currently breastfeeding
  • 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

Treatment and study plan

Angiotensin Receptor Blockers

Drug

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 names: Candesartan, Eprosartan, Irbesartan, Losartan, Olmesartan, Telmisartan, Valsartan

Placebo

Other

Placebo

Primary outcomes

  1. 7-Point National Institute of Health Clinical Health Score

    Time frame: 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;

    • 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;

Secondary outcomes

  1. 7-Point National Institute of Health Clinical Health Score

    Time frame: 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;

    • 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;

  2. Mortality

    Time frame: 28 Days

    To determine whether the addition of the intervention, compared to standard care, changes the risk of all cause mortality

  3. Mortality

    Time frame: 90 Days

    To determine whether the addition of the intervention, compared to standard care, changes the risk of all cause mortality

  4. Intensive Care Unit Admission

    Time frame: 28 Days

    To determine whether the addition of the intervention, compared to standard care, changes the count of all cause Intensive Care Unit admission

  5. Intensive Care Unit Admission

    Time frame: 90 Days

    To determine whether the addition of the intervention, compared to standard care, changes the count of all cause Intensive Care Unit admission

  6. Intensive Care Unit Number of Days

    Time frame: 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

  7. Respiratory Failure

    Time frame: 28 Days

    To determine whether the addition of the intervention, compared to standard care, changes the incidence of respiratory failure

  8. Dialysis Requirement

    Time frame: 28 Days

    To determine whether the addition of the intervention, compared to standard care, changes the requirements for dialysis

  9. Hospitalisation Days

    Time frame: 28 Days

    To determine whether the addition of the intervention, compared to standard care, changes the number of hospitalisation days

  10. Hospitalisation Days

    Time frame: 90 Days

    To determine whether the addition of the intervention, compared to standard care, changes the number of hospitalisation days

  11. Ventilator-Free Days

    Time frame: 28 Days

    To determine whether the addition of the intervention, compared to standard care, changes need for ventilation

  12. Dialysis Days

    Time frame: 28 Days

    To determine whether the addition of the intervention, compared to standard care, changes need for dialysis

  13. Acute Kidney Injury

    Time frame: 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

  14. Hypotension Requiring Vasopressors

    Time frame: 28 Days

    To determine whether the addition of the intervention, compared to standard care, changes risk of hypotension requiring vasopressors

Other outcomes

  1. Hyperkalaemia

    Time frame: Day 28

    To determine whether the addition of the intervention, compared to standard care, changes risk of hyperkalaemia.

  2. Oxygen Saturation

    Time frame: Day 28

    To determine whether the addition of the intervention, compared to standard care, changes risk of decreased oxygen saturation

  3. Oxygen Saturation

    Time frame: Day 14

    To determine whether the addition of the intervention, compared to standard care, changes risk of decreased oxygen saturation

Sponsors and collaborators

Lead sponsor

The George Institute

Other

Registry information

Acronym: CLARITY

Important dates

Study start
2020
Primary completion
2021
Study completion
2022
First posted
May 19, 2020
Registry last updated
Mar 17, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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