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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04394117




Registration number
NCT04394117
Ethics application status
Date submitted
18/05/2020
Date registered
19/05/2020

Titles & IDs
Public title
Controlled evaLuation of Angiotensin Receptor Blockers for COVID-19 respIraTorY Disease
Scientific title
Controlled evaLuation of Angiotensin Receptor Blockers for COVID-19 respIraTorY Disease
Secondary ID [1] 0 0
11052020
Universal Trial Number (UTN)
Trial acronym
CLARITY
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Coronavirus Disease 2019 0 0
COVID-19 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases
Respiratory 0 0 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Angiotensin Receptor Blockers
Other interventions - Placebo

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.

Placebo comparator: Standard Care + Placebo - Participants will receive a placebo on top of the standard care provided by their institution.


Treatment: Drugs: Angiotensin Receptor Blockers
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 interventions: Placebo
Placebo

Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
7-Point National Institute of Health Clinical Health Score
Timepoint [1] 0 0
14 Days
Secondary outcome [1] 0 0
7-Point National Institute of Health Clinical Health Score
Timepoint [1] 0 0
28 Days
Secondary outcome [2] 0 0
Mortality
Timepoint [2] 0 0
28 Days
Secondary outcome [3] 0 0
Mortality
Timepoint [3] 0 0
90 Days
Secondary outcome [4] 0 0
Intensive Care Unit Admission
Timepoint [4] 0 0
28 Days
Secondary outcome [5] 0 0
Intensive Care Unit Admission
Timepoint [5] 0 0
90 Days
Secondary outcome [6] 0 0
Intensive Care Unit Number of Days
Timepoint [6] 0 0
90 Days
Secondary outcome [7] 0 0
Respiratory Failure
Timepoint [7] 0 0
28 Days
Secondary outcome [8] 0 0
Dialysis Requirement
Timepoint [8] 0 0
28 Days
Secondary outcome [9] 0 0
Hospitalisation Days
Timepoint [9] 0 0
28 Days
Secondary outcome [10] 0 0
Hospitalisation Days
Timepoint [10] 0 0
90 Days
Secondary outcome [11] 0 0
Ventilator-Free Days
Timepoint [11] 0 0
28 Days
Secondary outcome [12] 0 0
Dialysis Days
Timepoint [12] 0 0
28 Days
Secondary outcome [13] 0 0
Acute Kidney Injury
Timepoint [13] 0 0
28 Days
Secondary outcome [14] 0 0
Hypotension Requiring Vasopressors
Timepoint [14] 0 0
28 Days

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 0 0
Canterbury Hospital - Campsie
Recruitment hospital [3] 0 0
The Sutherland Hospital - Caringbah
Recruitment hospital [4] 0 0
Concord Hospital - Concord
Recruitment hospital [5] 0 0
St George Hospital - Kogarah
Recruitment hospital [6] 0 0
Liverpool Hospital - Liverpool
Recruitment hospital [7] 0 0
John Hunter Hospital - New Lambton Heights
Recruitment hospital [8] 0 0
Prince of Wales Hospital - Randwick
Recruitment hospital [9] 0 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [10] 0 0
Westmead Hospital - Westmead
Recruitment hospital [11] 0 0
Wollongong Hospital - Wollongong
Recruitment hospital [12] 0 0
Northern Health - Epping
Recruitment hospital [13] 0 0
Austin Health - Heidelberg
Recruitment hospital [14] 0 0
Alfred Health - Melbourne
Recruitment hospital [15] 0 0
Western Health - St Albans
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2194 - Campsie
Recruitment postcode(s) [3] 0 0
2229 - Caringbah
Recruitment postcode(s) [4] 0 0
2139 - Concord
Recruitment postcode(s) [5] 0 0
2217 - Kogarah
Recruitment postcode(s) [6] 0 0
2170 - Liverpool
Recruitment postcode(s) [7] 0 0
2305 - New Lambton Heights
Recruitment postcode(s) [8] 0 0
2031 - Randwick
Recruitment postcode(s) [9] 0 0
2065 - St Leonards
Recruitment postcode(s) [10] 0 0
2145 - Westmead
Recruitment postcode(s) [11] 0 0
2500 - Wollongong
Recruitment postcode(s) [12] 0 0
3076 - Epping
Recruitment postcode(s) [13] 0 0
3084 - Heidelberg
Recruitment postcode(s) [14] 0 0
3004 - Melbourne
Recruitment postcode(s) [15] 0 0
3021 - St Albans
Recruitment outside Australia
Country [1] 0 0
India
State/province [1] 0 0
Chandigarh
Country [2] 0 0
India
State/province [2] 0 0
Delhi
Country [3] 0 0
India
State/province [3] 0 0
Manipal
Country [4] 0 0
India
State/province [4] 0 0
Nabarangpur
Country [5] 0 0
India
State/province [5] 0 0
Pune
Country [6] 0 0
India
State/province [6] 0 0
Raipur

Funding & Sponsors
Primary sponsor type
Other
Name
The George Institute
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Meg Jardine
Address 0 0
University of Sydney
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
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 document/s available: Study protocol, Informed consent form (ICF), Clinical study report (CSR)
When will data be available (start and end dates)?
To be confirmed
Available to whom?
To be determined
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.