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

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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

Tracking Information
First Submitted Date  ICMJE May 18, 2020
First Posted Date  ICMJE May 19, 2020
Last Update Posted Date December 24, 2020
Actual Study Start Date  ICMJE June 19, 2020
Estimated Primary Completion Date June 30, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 22, 2020)
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;
Original Primary Outcome Measures  ICMJE
 (submitted: May 18, 2020)
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;
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 22, 2020)
  • 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;
  • Mortality [ Time Frame: 28 Days ]
    To determine whether the addition of the intervention, compared to standard care, changes the risk of all cause mortality
  • Mortality [ Time Frame: 90 Days ]
    To determine whether the addition of the intervention, compared to standard care, changes the risk of all cause mortality
  • 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
  • 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
  • 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
  • Respiratory Failure [ Time Frame: 28 Days ]
    To determine whether the addition of the intervention, compared to standard care, changes the incidence of respiratory failure
  • Dialysis Requirement [ Time Frame: 28 Days ]
    To determine whether the addition of the intervention, compared to standard care, changes the requirements for dialysis
  • Hospitalisation Days [ Time Frame: 28 Days ]
    To determine whether the addition of the intervention, compared to standard care, changes the number of hospitalisation days
  • Hospitalisation Days [ Time Frame: 90 Days ]
    To determine whether the addition of the intervention, compared to standard care, changes the number of hospitalisation days
  • Ventilator-Free Days [ Time Frame: 28 Days ]
    To determine whether the addition of the intervention, compared to standard care, changes need for ventilation
  • Dialysis Days [ Time Frame: 28 Days ]
    To determine whether the addition of the intervention, compared to standard care, changes need for dialysis
  • 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
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: May 18, 2020)
  • 7-Point National Institute of Health Clinical Health Score [ Time Frame: 15 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;
  • Mortality [ Time Frame: 28 Days ]
    To determine whether the addition of the intervention, compared to standard care, changes the risk of all cause mortality
  • Mortality [ Time Frame: 90 Days ]
    To determine whether the addition of the intervention, compared to standard care, changes the risk of all cause mortality
  • 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
  • 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
  • Intensive Care Unit Admission [ 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
  • Respiratory Failure [ Time Frame: 90 Days ]
    To determine whether the addition of the intervention, compared to standard care, changes the incidence of respiratory failure
  • Dialysis Requirement [ Time Frame: 90 Days ]
    To determine whether the addition of the intervention, compared to standard care, changes the requirements for dialysis
  • Hospitalisation Days [ Time Frame: 28 Days ]
    To determine whether the addition of the intervention, compared to standard care, changes the number of hospitalisation days
  • Hospitalisation Days [ Time Frame: 90 Days ]
    To determine whether the addition of the intervention, compared to standard care, changes the number of hospitalisation days
  • Ventilator-Free Days [ Time Frame: 28 Days ]
    To determine whether the addition of the intervention, compared to standard care, changes need for ventilation
  • Dialysis Days [ Time Frame: 28 Days ]
    To determine whether the addition of the intervention, compared to standard care, changes need for dialysis
  • 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
  • Hypotension Requiring Vasopressors [ Time Frame: 90 Days ]
    To determine whether the addition of the intervention, compared to standard care, changes risk of hypotension requiring vasopressors
Current Other Pre-specified Outcome Measures
 (submitted: December 22, 2020)
  • Hyperkalaemia [ Time Frame: Day 28 ]
    To determine whether the addition of the intervention, compared to standard care, changes risk of hyperkalaemia.
  • Oxygen Saturation [ Time Frame: Day 28 ]
    To determine whether the addition of the intervention, compared to standard care, changes risk of decreased oxygen saturation
  • Oxygen Saturation [ Time Frame: Day 14 ]
    To determine whether the addition of the intervention, compared to standard care, changes risk of decreased oxygen saturation
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Controlled evaLuation of Angiotensin Receptor Blockers for COVID-19 respIraTorY Disease
Official Title  ICMJE Controlled evaLuation of Angiotensin Receptor Blockers for COVID-19 respIraTorY Disease
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 Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE 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
Condition  ICMJE
  • SARS-Cov-2
  • COVID-19
Intervention  ICMJE
  • 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
  • Other: Placebo
    Placebo
Study Arms  ICMJE
  • 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.
    Intervention: Drug: Angiotensin Receptor Blockers
  • Placebo Comparator: Standard Care + Placebo
    Participants will receive a placebo on top of the standard care provided by their institution.
    Intervention: Other: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 22, 2020)
1500
Original Estimated Enrollment  ICMJE
 (submitted: May 18, 2020)
605
Estimated Study Completion Date  ICMJE August 30, 2021
Estimated Primary Completion Date June 30, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
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
Listed Location Countries  ICMJE Australia,   India
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04394117
Other Study ID Numbers  ICMJE 11052020
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
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
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Time Frame: To be confirmed
Access Criteria: To be determined
Responsible Party The George Institute
Study Sponsor  ICMJE The George Institute
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Meg Jardine National Health and Medical Research Council, Australia
PRS Account The George Institute
Verification Date December 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP