search
Back to results

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

Primary Purpose

Coronavirus Disease 2019, COVID-19

Status
Completed
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
Angiotensin Receptor Blockers
Placebo
Sponsored by
The George Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Coronavirus Disease 2019 focused on measuring Angiotensin Receptor Blocker (ARB), Angiotensin Converting Enzyme 2 (ACE2), Coronavirus Disease 2019 (COVID-19), Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-Cov-2)

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Royal Prince Alfred Hospital
  • Canterbury Hospital
  • The Sutherland Hospital
  • Concord Hospital
  • St George Hospital
  • Liverpool Hospital
  • John Hunter Hospital
  • Prince of Wales Hospital
  • Royal North Shore Hospital
  • Westmead Hospital
  • Wollongong Hospital
  • Northern Health
  • Austin Health
  • Alfred Health
  • Western Health
  • Government Medical College & Hospital
  • Post Graduate Institute of Medical Education & Research
  • Lok Nayak Jai Prakash
  • Kasturba Medical College
  • Christian Hospital
  • Jivenrekha Hospital
  • All India Institute of Medical Science

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Standard Care + Angiotensin Receptor Blocker (ARB)

Standard Care + Placebo

Arm Description

Participants will receive an Angiotensin Receptor Blocker on top of the standard care provided by their institution.

Participants will receive a placebo on top of the standard care provided by their institution.

Outcomes

Primary Outcome Measures

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;

Secondary Outcome Measures

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;
Mortality
To determine whether the addition of the intervention, compared to standard care, changes the risk of all cause mortality
Mortality
To determine whether the addition of the intervention, compared to standard care, changes the risk of all cause mortality
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
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
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
Respiratory Failure
To determine whether the addition of the intervention, compared to standard care, changes the incidence of respiratory failure
Dialysis Requirement
To determine whether the addition of the intervention, compared to standard care, changes the requirements for dialysis
Hospitalisation Days
To determine whether the addition of the intervention, compared to standard care, changes the number of hospitalisation days
Hospitalisation Days
To determine whether the addition of the intervention, compared to standard care, changes the number of hospitalisation days
Ventilator-Free Days
To determine whether the addition of the intervention, compared to standard care, changes need for ventilation
Dialysis Days
To determine whether the addition of the intervention, compared to standard care, changes need for dialysis
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
Hypotension Requiring Vasopressors
To determine whether the addition of the intervention, compared to standard care, changes risk of hypotension requiring vasopressors

Full Information

First Posted
May 18, 2020
Last Updated
March 2, 2022
Sponsor
The George Institute
search

1. Study Identification

Unique Protocol Identification Number
NCT04394117
Brief Title
Controlled evaLuation of Angiotensin Receptor Blockers for COVID-19 respIraTorY Disease
Acronym
CLARITY
Official Title
Controlled evaLuation of Angiotensin Receptor Blockers for COVID-19 respIraTorY Disease
Study Type
Interventional

2. Study Status

Record Verification Date
March 2022
Overall Recruitment Status
Completed
Study Start Date
June 19, 2020 (Actual)
Primary Completion Date
November 14, 2021 (Actual)
Study Completion Date
January 17, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
The George Institute

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Coronavirus Disease 2019, COVID-19
Keywords
Angiotensin Receptor Blocker (ARB), Angiotensin Converting Enzyme 2 (ACE2), Coronavirus Disease 2019 (COVID-19), Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-Cov-2)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
CLARITY is a randomised control trial of two parallel groups; Standard Care + Angiotensin Receptor Blocker (ARB) 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
Outcomes Assessor
Masking Description
Trial Statistician and sponsor staff will remain blinded to treatment allocation throughout the trial.
Allocation
Randomized
Enrollment
787 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Standard Care + Angiotensin Receptor Blocker (ARB)
Arm Type
Active Comparator
Arm Description
Participants will receive an Angiotensin Receptor Blocker on top of the standard care provided by their institution.
Arm Title
Standard Care + Placebo
Arm Type
Placebo Comparator
Arm Description
Participants will receive a placebo on top of the standard care provided by their institution.
Intervention Type
Drug
Intervention Name(s)
Angiotensin Receptor Blockers
Other Intervention Name(s)
Candesartan, Eprosartan, Irbesartan, Losartan, Olmesartan, Telmisartan, Valsartan
Intervention Description
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
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Placebo
Primary Outcome Measure Information:
Title
7-Point National Institute of Health Clinical Health Score
Description
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;
Time Frame
14 Days
Secondary Outcome Measure Information:
Title
7-Point National Institute of Health Clinical Health Score
Description
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;
Time Frame
28 Days
Title
Mortality
Description
To determine whether the addition of the intervention, compared to standard care, changes the risk of all cause mortality
Time Frame
28 Days
Title
Mortality
Description
To determine whether the addition of the intervention, compared to standard care, changes the risk of all cause mortality
Time Frame
90 Days
Title
Intensive Care Unit Admission
Description
To determine whether the addition of the intervention, compared to standard care, changes the count of all cause Intensive Care Unit admission
Time Frame
28 Days
Title
Intensive Care Unit Admission
Description
To determine whether the addition of the intervention, compared to standard care, changes the count of all cause Intensive Care Unit admission
Time Frame
90 Days
Title
Intensive Care Unit Number of Days
Description
To determine whether the addition of the intervention, compared to standard care, changes the number of days total, of intensive care unit admission
Time Frame
90 Days
Title
Respiratory Failure
Description
To determine whether the addition of the intervention, compared to standard care, changes the incidence of respiratory failure
Time Frame
28 Days
Title
Dialysis Requirement
Description
To determine whether the addition of the intervention, compared to standard care, changes the requirements for dialysis
Time Frame
28 Days
Title
Hospitalisation Days
Description
To determine whether the addition of the intervention, compared to standard care, changes the number of hospitalisation days
Time Frame
28 Days
Title
Hospitalisation Days
Description
To determine whether the addition of the intervention, compared to standard care, changes the number of hospitalisation days
Time Frame
90 Days
Title
Ventilator-Free Days
Description
To determine whether the addition of the intervention, compared to standard care, changes need for ventilation
Time Frame
28 Days
Title
Dialysis Days
Description
To determine whether the addition of the intervention, compared to standard care, changes need for dialysis
Time Frame
28 Days
Title
Acute Kidney Injury
Description
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
Time Frame
28 Days
Title
Hypotension Requiring Vasopressors
Description
To determine whether the addition of the intervention, compared to standard care, changes risk of hypotension requiring vasopressors
Time Frame
28 Days
Other Pre-specified Outcome Measures:
Title
Hyperkalaemia
Description
To determine whether the addition of the intervention, compared to standard care, changes risk of hyperkalaemia.
Time Frame
Day 28
Title
Oxygen Saturation
Description
To determine whether the addition of the intervention, compared to standard care, changes risk of decreased oxygen saturation
Time Frame
Day 28
Title
Oxygen Saturation
Description
To determine whether the addition of the intervention, compared to standard care, changes risk of decreased oxygen saturation
Time Frame
Day 14

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Meg Jardine
Organizational Affiliation
University of Sydney
Official's Role
Study Chair
Facility Information:
Facility Name
Royal Prince Alfred Hospital
City
Camperdown
State/Province
New South Wales
ZIP/Postal Code
2050
Country
Australia
Facility Name
Canterbury Hospital
City
Campsie
State/Province
New South Wales
ZIP/Postal Code
2194
Country
Australia
Facility Name
The Sutherland Hospital
City
Caringbah
State/Province
New South Wales
ZIP/Postal Code
2229
Country
Australia
Facility Name
Concord Hospital
City
Concord
State/Province
New South Wales
ZIP/Postal Code
2139
Country
Australia
Facility Name
St George Hospital
City
Kogarah
State/Province
New South Wales
ZIP/Postal Code
2217
Country
Australia
Facility Name
Liverpool Hospital
City
Liverpool
State/Province
New South Wales
ZIP/Postal Code
2170
Country
Australia
Facility Name
John Hunter Hospital
City
New Lambton Heights
State/Province
New South Wales
ZIP/Postal Code
2305
Country
Australia
Facility Name
Prince of Wales Hospital
City
Randwick
State/Province
New South Wales
ZIP/Postal Code
2031
Country
Australia
Facility Name
Royal North Shore Hospital
City
St Leonards
State/Province
New South Wales
ZIP/Postal Code
2065
Country
Australia
Facility Name
Westmead Hospital
City
Westmead
State/Province
New South Wales
ZIP/Postal Code
2145
Country
Australia
Facility Name
Wollongong Hospital
City
Wollongong
State/Province
New South Wales
ZIP/Postal Code
2500
Country
Australia
Facility Name
Northern Health
City
Epping
State/Province
Victoria
ZIP/Postal Code
3076
Country
Australia
Facility Name
Austin Health
City
Heidelberg
State/Province
Victoria
ZIP/Postal Code
3084
Country
Australia
Facility Name
Alfred Health
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3004
Country
Australia
Facility Name
Western Health
City
St Albans
State/Province
Victoria
ZIP/Postal Code
3021
Country
Australia
Facility Name
Government Medical College & Hospital
City
Chandigarh
Country
India
Facility Name
Post Graduate Institute of Medical Education & Research
City
Chandigarh
Country
India
Facility Name
Lok Nayak Jai Prakash
City
Delhi
Country
India
Facility Name
Kasturba Medical College
City
Manipal
Country
India
Facility Name
Christian Hospital
City
Nabarangpur
Country
India
Facility Name
Jivenrekha Hospital
City
Pune
Country
India
Facility Name
All India Institute of Medical Science
City
Raipur
Country
India

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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.
IPD Sharing Time Frame
To be confirmed
IPD Sharing Access Criteria
To be determined
Citations:
PubMed Identifier
36384746
Citation
Jardine MJ, Kotwal SS, Bassi A, Hockham C, Jones M, Wilcox A, Pollock C, Burrell LM, McGree J, Rathore V, Jenkins CR, Gupta L, Ritchie A, Bangi A, D'Cruz S, McLachlan AJ, Finfer S, Cummins MM, Snelling T, Jha V; CLARITY trial investigators. Angiotensin receptor blockers for the treatment of covid-19: pragmatic, adaptive, multicentre, phase 3, randomised controlled trial. BMJ. 2022 Nov 16;379:e072175. doi: 10.1136/bmj-2022-072175.
Results Reference
derived
PubMed Identifier
35477480
Citation
McGree JM, Hockham C, Kotwal S, Wilcox A, Bassi A, Pollock C, Burrell LM, Snelling T, Jha V, Jardine M, Jones M; CLARITY Trial Steering Committee. Controlled evaLuation of Angiotensin Receptor Blockers for COVID-19 respIraTorY disease (CLARITY): statistical analysis plan for a randomised controlled Bayesian adaptive sample size trial. Trials. 2022 Apr 27;23(1):361. doi: 10.1186/s13063-022-06167-2.
Results Reference
derived
PubMed Identifier
34454580
Citation
Hockham C, Kotwal S, Wilcox A, Bassi A, McGree J, Pollock C, Burrell LM, Bathla N, Kunigari M, Rathore V, John M, Lin E, Jenkins C, Ritchie A, McLachlan A, Snelling T, Jones M, Jha V, Jardine M; CLARITY Investigators. Protocol for the Controlled evaLuation of Angiotensin Receptor blockers for COVID-19 respIraTorY disease (CLARITY): a randomised controlled trial. Trials. 2021 Aug 28;22(1):573. doi: 10.1186/s13063-021-05521-0.
Results Reference
derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs