Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04394117
Recruitment Status : Recruiting
First Posted : May 19, 2020
Last Update Posted : December 24, 2020
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
SARS-Cov-2 COVID-19 Drug: Angiotensin Receptor Blockers Other: Placebo Phase 4

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1500 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

CLARITY is a randomised control trial of two parallel groups;

  1. Standard Care + Angiotensin Receptor Blocker (ARB)
  2. Standard Care

Participants will be randomised in a 1:1 ratio. Randomisation will be stratified according to country and whether the participant is planned for hospital admission or home-based care.

Masking: Single (Outcomes Assessor)
Masking Description: Trial Statistician and sponsor staff will remain blinded to treatment allocation throughout the trial.
Primary Purpose: Treatment
Official Title: Controlled evaLuation of Angiotensin Receptor Blockers for COVID-19 respIraTorY Disease
Actual Study Start Date : June 19, 2020
Estimated Primary Completion Date : June 30, 2021
Estimated Study Completion Date : August 30, 2021

Arm Intervention/treatment
Active Comparator: Standard Care + Angiotensin Receptor Blocker (ARB)
Participants will receive an Angiotensin Receptor Blocker on top of the standard care provided by their institution.
Drug: Angiotensin Receptor Blockers

Angiotensin Receptor Blockers class 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 by competitive antagonism of the angiotensin receptor. ARBs displace angiotensin II from the angiotensin I receptor and produce their protective effects by reducing the downstream effects of angiotensin II-induced vasoconstriction, aldosterone release, catecholamine release, arginine vasopressin release, water intake, and hypertrophic response.

The virus causing COVID-19, the SARS-CoV-2 virus binds to the extracellular portion of 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 Comparator: Standard Care + Placebo
Participants will receive a placebo on top of the standard care provided by their institution.
Other: Placebo
Placebo




Primary Outcome Measures :
  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;

    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 :
  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;

    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;

  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 idney 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 Outcome Measures:
  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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Potential participants must satisfy all of the following:

  1. Laboratory-confirmed* diagnosis of SARS-CoV-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-RAASi 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. BMI ≥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 ACEi, ARB 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04394117


Contacts
Layout table for location contacts
Contact: Meg Jardine +61 2 9562 5000 Meg.jardine@ctc.usyd.edu.au
Contact: Arlen Wilcox +61 2 9562 5203 Arlen.wilcox@ctc.usyd.edu.au

Locations
Show Show 19 study locations
Sponsors and Collaborators
The George Institute
Investigators
Layout table for investigator information
Study Chair: Meg Jardine National Health and Medical Research Council, Australia
Layout table for additonal information
Responsible Party: The George Institute
ClinicalTrials.gov Identifier: NCT04394117    
Other Study ID Numbers: 11052020
First Posted: May 19, 2020    Key Record Dates
Last Update Posted: December 24, 2020
Last Verified: December 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

Trial data will be disseminated in the form of a publication to a relevant clinical journal and presentation at appropriate scientific conferences.

Individual participant data that underlie the results reported, after de-identification (text, tables, figures, and appendices), may be shared with Investigators whose proposed use of the data has been approved by an independent review committee ("learned intermediary") identified for this purpose.

Supporting Materials: Study Protocol
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: To be confirmed
Access Criteria: To be determined

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by The George Institute:
Angiotensin Receptor Blocker (ARB)
Angiotensin Converting Enzyme 2 (ACE2)
COVID-19
SARS-Cov-2
Additional relevant MeSH terms:
Layout table for MeSH terms
Respiration Disorders
Respiratory Tract Diseases
Losartan
Valsartan
Telmisartan
Candesartan
Olmesartan
Irbesartan
Eprosartan
Angiotensin Receptor Antagonists
Antihypertensive Agents
Angiotensin II Type 1 Receptor Blockers
Molecular Mechanisms of Pharmacological Action
Anti-Arrhythmia Agents
Angiotensin II Type 2 Receptor Blockers