Clinical trial NCT04394117: Controlled evaLuation of Angiotensin Receptor Blockers for COVID-19 respIraTorY Disease
Official title: Controlled evaLuation of Angiotensin Receptor Blockers for COVID-19 respIraTorY Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: 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)
Lead sponsor: The George Institute
Sponsor class: OTHER
First posted: 2020-05-19
Enrollment: 787
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: 7-Point National Institute of Health Clinical Health Score
timeFrame: 14 Days
Secondary outcomes:
measure: 7-Point National Institute of Health Clinical Health Score
timeFrame: 28 Days
measure: Mortality
timeFrame: 28 Days
measure: Mortality
timeFrame: 90 Days
measure: Intensive Care Unit Admission
timeFrame: 28 Days
measure: Intensive Care Unit Admission
timeFrame: 90 Days
measure: Intensive Care Unit Number of Days
timeFrame: 90 Days
measure: Respiratory Failure
timeFrame: 28 Days
measure: Dialysis Requirement
timeFrame: 28 Days
measure: Hospitalisation Days
timeFrame: 28 Days
measure: Hospitalisation Days
timeFrame: 90 Days
measure: Ventilator-Free Days
timeFrame: 28 Days
measure: Dialysis Days
timeFrame: 28 Days
measure: Acute Kidney Injury
timeFrame: 28 Days
measure: Hypotension Requiring Vasopressors
timeFrame: 28 Days
Other outcomes:
measure: Hyperkalaemia
timeFrame: Day 28
measure: Oxygen Saturation
timeFrame: Day 28
measure: Oxygen Saturation
timeFrame: Day 14
Locations:
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: Campsie
country: Australia
facility: Canterbury Hospital
state: New South Wales
city: Caringbah
country: Australia
facility: The Sutherland Hospital
state: New South Wales
city: Concord
country: Australia
facility: Concord Hospital
state: New South Wales
city: Kogarah
country: Australia
facility: St George Hospital
state: New South Wales
city: Liverpool
country: Australia
facility: Liverpool Hospital
state: New South Wales
city: New Lambton Heights
country: Australia
facility: John Hunter Hospital
state: New South Wales
city: Randwick
country: Australia
facility: Prince of Wales Hospital
state: New South Wales
city: St Leonards
country: Australia
facility: Royal North Shore Hospital
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Wollongong
country: Australia
facility: Wollongong Hospital
state: New South Wales
city: Epping
country: Australia
facility: Northern Health
state: Victoria
city: Heidelberg
country: Australia
facility: Austin Health
state: Victoria
city: Melbourne
country: Australia
facility: Alfred Health
state: Victoria
city: St Albans
country: Australia
facility: Western Health
state: Victoria
city: Chandigarh
country: India
facility: Government Medical College & Hospital
city: Chandigarh
country: India
facility: Post Graduate Institute of Medical Education & Research
city: Delhi
country: India
facility: Lok Nayak Jai Prakash
city: Manipal
country: India
facility: Kasturba Medical College
city: Nabarangpur
country: India
facility: Christian Hospital
city: Pune
country: India
facility: Jivenrekha Hospital
city: Raipur
country: India
facility: All India Institute of Medical Science
Study officials:
affiliation: University of Sydney
name: Meg Jardine
role: STUDY_CHAIR
References:
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.
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.
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.