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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT04394117
Ethics application status
Date submitted
18/05/2020
Date registered
19/05/2020
Date last updated
16/07/2020

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:
SARS-Cov-2 0 0
COVID-19 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Other respiratory disorders / diseases

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

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.

No Intervention: Standard Care - Participants will receive on the standard care provided by their institution.


Treatment: Drugs: 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.

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

Outcomes
Primary outcome [1] 0 0
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;
Timepoint [1] 0 0
28 Days
Secondary outcome [1] 0 0
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;
Timepoint [1] 0 0
15 Days
Secondary outcome [2] 0 0
Mortality - To determine whether the addition of the intervention, compared to standard care, changes the risk of all cause mortality
Timepoint [2] 0 0
28 Days
Secondary outcome [3] 0 0
Mortality - To determine whether the addition of the intervention, compared to standard care, changes the risk of all cause mortality
Timepoint [3] 0 0
90 Days
Secondary outcome [4] 0 0
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
Timepoint [4] 0 0
28 Days
Secondary outcome [5] 0 0
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
Timepoint [5] 0 0
90 Days
Secondary outcome [6] 0 0
Intensive Care Unit Admission - To determine whether the addition of the intervention, compared to standard care, changes the number of days total, of intensive care unit admission
Timepoint [6] 0 0
90 Days
Secondary outcome [7] 0 0
Respiratory Failure - To determine whether the addition of the intervention, compared to standard care, changes the incidence of respiratory failure
Timepoint [7] 0 0
90 Days
Secondary outcome [8] 0 0
Dialysis Requirement - To determine whether the addition of the intervention, compared to standard care, changes the requirements for dialysis
Timepoint [8] 0 0
90 Days
Secondary outcome [9] 0 0
Hospitalisation Days - To determine whether the addition of the intervention, compared to standard care, changes the number of hospitalisation days
Timepoint [9] 0 0
28 Days
Secondary outcome [10] 0 0
Hospitalisation Days - To determine whether the addition of the intervention, compared to standard care, changes the number of hospitalisation days
Timepoint [10] 0 0
90 Days
Secondary outcome [11] 0 0
Ventilator-Free Days - To determine whether the addition of the intervention, compared to standard care, changes need for ventilation
Timepoint [11] 0 0
28 Days
Secondary outcome [12] 0 0
Dialysis Days - To determine whether the addition of the intervention, compared to standard care, changes need for dialysis
Timepoint [12] 0 0
28 Days
Secondary outcome [13] 0 0
Acute Kidney Injury - 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
Timepoint [13] 0 0
28 Days
Secondary outcome [14] 0 0
Hypotension Requiring Vasopressors - To determine whether the addition of the intervention, compared to standard care, changes risk of hypotension requiring vasopressors
Timepoint [14] 0 0
90 Days

Eligibility
Key inclusion criteria
Potential participants must satisfy all of the following:

1. Laboratory-confirmed diagnosis of SARS-CoV-2 infection

2. Age = 18 years

3. a) Systolic Blood Pressure (SBP) = 125 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 staff are willing and able to perform trial procedures.

5. Either Intended for hospital admission for management of COVID-19, or

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 with HbA1c =7% or on glucose lowering medication

4. History of cardiovascular disease

5. History of chronic respiratory illness

6. Currently treated with immunosuppression

6. a) For those intended for hospital admission, the diagnosis (i.e. date of test result)
for SARS-CoV-2 infection must be within 3 days prior to randomisation, OR b) For those
intended for management at home, the diagnosis (i.e. date of test result) for
SARS-CoV-2 infection must be within 7 days prior to randomisation
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Currently treated with an ACEi, ARB or aldosterone antagonist, aliskeren, or
angiotensin receptor-neprilysin inhibitors (ARNi)

2. Serum potassium > 5.2 mmol/L or no potassium testing within the last 3 months

3. a) For those intended for hospital admission, an estimated Glomerular Filtration Rate
(eGFR) <30ml/min/1.732 or no eGFR testing within the last 3 months, OR b) For those
intended for management at home, an eGFR <45ml/min/1.732 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. Women younger than 51 years who have not had a negative pregnancy test during the past
3 days

8. Women younger than 51 years who do not agree to use adequate contraception

9. Women who are currently breastfeeding

10. 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
Recruiting
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
Royal prince Alfred Virtual Hospital - Camperdown
Recruitment hospital [3] 0 0
Canterbury Hospital - Campsie
Recruitment hospital [4] 0 0
Concord Hospital - Concord
Recruitment hospital [5] 0 0
St George Hospital - Kogarah
Recruitment hospital [6] 0 0
John Hunter Hospital - New Lambton Heights
Recruitment hospital [7] 0 0
Prince of Wales Hospital - Randwick
Recruitment hospital [8] 0 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [9] 0 0
Westmead Hospital - Westmead
Recruitment hospital [10] 0 0
Wollongong Hospital - Wollongong
Recruitment hospital [11] 0 0
Austin Health - Heidelberg
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2194 - Campsie
Recruitment postcode(s) [3] 0 0
2139 - Concord
Recruitment postcode(s) [4] 0 0
2217 - Kogarah
Recruitment postcode(s) [5] 0 0
2305 - New Lambton Heights
Recruitment postcode(s) [6] 0 0
2031 - Randwick
Recruitment postcode(s) [7] 0 0
2065 - St Leonards
Recruitment postcode(s) [8] 0 0
2145 - Westmead
Recruitment postcode(s) [9] 0 0
2500 - Wollongong
Recruitment postcode(s) [10] 0 0
3084 - Heidelberg

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

Ethics approval
Ethics application status

Summary
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 website
https://clinicaltrials.gov/show/NCT04394117
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Meg Jardine
Address 0 0
The George Institute
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Meg Jardine
Address 0 0
Country 0 0
Phone 0 0
+61 2 8052 4530
Fax 0 0
Email 0 0
mjardine@georgeinstitute.org.au
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04394117