Controlled evaLuation of Angiotensin Receptor Blockers for COVID-19 respIraTorY Disease
CLARITY
1 other identifier
interventional
787
2 countries
22
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_4
Started Jun 2020
22 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 18, 2020
CompletedFirst Posted
Study publicly available on registry
May 19, 2020
CompletedStudy Start
First participant enrolled
June 19, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 14, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
January 17, 2022
CompletedMarch 17, 2022
March 1, 2022
1.4 years
May 18, 2020
March 2, 2022
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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; 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;
14 Days
Secondary Outcomes (14)
7-Point National Institute of Health Clinical Health Score
28 Days
Mortality
28 Days
Mortality
90 Days
Intensive Care Unit Admission
28 Days
Intensive Care Unit Admission
90 Days
- +9 more secondary outcomes
Other Outcomes (3)
Hyperkalaemia
Day 28
Oxygen Saturation
Day 28
Oxygen Saturation
Day 14
Study Arms (2)
Standard Care + Angiotensin Receptor Blocker (ARB)
ACTIVE COMPARATORParticipants will receive an Angiotensin Receptor Blocker on top of the standard care provided by their institution.
Standard Care + Placebo
PLACEBO COMPARATORParticipants will receive a placebo on top of the standard care provided by their institution.
Interventions
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
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (22)
Royal Prince Alfred Hospital
Camperdown, New South Wales, 2050, Australia
Canterbury Hospital
Campsie, New South Wales, 2194, Australia
The Sutherland Hospital
Caringbah, New South Wales, 2229, Australia
Concord Hospital
Concord, New South Wales, 2139, Australia
St George Hospital
Kogarah, New South Wales, 2217, Australia
Liverpool Hospital
Liverpool, New South Wales, 2170, Australia
John Hunter Hospital
New Lambton Heights, New South Wales, 2305, Australia
Prince of Wales Hospital
Randwick, New South Wales, 2031, Australia
Royal North Shore Hospital
St Leonards, New South Wales, 2065, Australia
Westmead Hospital
Westmead, New South Wales, 2145, Australia
Wollongong Hospital
Wollongong, New South Wales, 2500, Australia
Northern Health
Epping, Victoria, 3076, Australia
Austin Health
Heidelberg, Victoria, 3084, Australia
Alfred Health
Melbourne, Victoria, 3004, Australia
Western Health
St Albans, Victoria, 3021, Australia
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
Nowrangapur, India
Jivenrekha Hospital
Pune, India
All India Institute of Medical Science
Raipur, India
Related Publications (3)
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.
PMID: 36384746DERIVEDMcGree 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.
PMID: 35477480DERIVEDHockham 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.
PMID: 34454580DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
Meg Jardine
University of Sydney
Study Design
- Study Type
- interventional
- Phase
- phase 4
- Allocation
- RANDOMIZED
- Masking
- SINGLE
- Who Masked
- OUTCOMES ASSESSOR
- Masking Details
- Trial Statistician and sponsor staff will remain blinded to treatment allocation throughout the trial.
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 18, 2020
First Posted
May 19, 2020
Study Start
June 19, 2020
Primary Completion
November 14, 2021
Study Completion
January 17, 2022
Last Updated
March 17, 2022
Record last verified: 2022-03
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, ICF, CSR
- Time Frame
- To be confirmed
- Access Criteria
- To be determined
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.