CTRI Number	CTRI/2020/07/026831 [Registered on: 27/07/2020] Trial Registered Prospectively
Last Modified On:	01/12/2022
Post Graduate Thesis	No
Type of Trial	Interventional
Type of Study	Drug
Study Design	Randomized, Parallel Group, Active Controlled Trial
Public Title of Study	Controlled evaluation of Angiotensin Receptor Blockers for COVID-19 Respiratory Disease
Scientific Title of Study	Controlled evaLuation of Angiotensin Receptor Blockers for COVID-19 Respiratory Disease
Secondary IDs if Any	Secondary ID  Registry  NIL  NIL
Details of Principal Investigator or overall Trial Coordinator (multi-center study) Modification(s)	Name  Professor Vivekanand Jha  Address  311-312, Third Floor, Elegance Tower Plot No. 8, Jasola District Centre New Delhi, India New Delhi DELHI 110025 India  Phone  911141588091   Fax  911141588090   Email  vjha@georgeinstitute.org.in
Details Contact Person Scientific Query Modification(s)	Name  Professor Vivekanand Jha  Address  311-312, Third Floor, Elegance Tower Plot No. 8, Jasola District Centre New Delhi, India New Delhi DELHI 110025 India  Phone  911141588091   Fax  911141588090   Email  vjha@georgeinstitute.org.in
Details Contact Person Public Query Modification(s)	Name  Professor Vivekanand Jha  Address  311-312, Third Floor, Elegance Tower Plot No. 8, Jasola District Centre New Delhi, India New Delhi DELHI 110025 India  Phone  911141588091   Fax  911141588090   Email  vjha@georgeinstitute.org.in
Source of Monetary or Material Support Modification(s)	George Institute for Global Health India, 311-312, Third Floor, Elegance Tower Plot No. 8, Jasola District Centre New Delhi, India
Primary Sponsor	Name  George Institute for Global Health India  Address  311-312, Third Floor, Elegance Tower Plot No. 8, Jasola District Centre New Delhi 110025  Type of Sponsor  Research institution
Details of Secondary Sponsor	Name  Address  NIL  NIL
Countries of Recruitment	India
Sites of Study Modification(s)	No of Sites = 7   Contact Person  Name of Site  Site Address  Phone/Fax/Email  Vinay Rathore  All India Institute of Medical Sciences  Gate No, 1, Great Eastern Rd, opposite Gurudwara, AIIMS Campus, Tatibandh, Raipur, Chhattisgarh 492099 Raipur   9914699651 vinayrathoredm@aiimsraipur.edu.in  Michael John  Christian Hospital  NH 201, Nowrangpur, Odisha 764059 Nabarangapur   8763394532 mjjohn6854@gmail.com  Sanjay Dcruz  Government Medical College & Hospital,  Chandi Path, Sector 32B, 32B, Sector 32, Chandigarh, 160047 Chandigarh   9646121556 sanjaydcruz@gmch.gov.in  Ashpak Bangi  Jivanrekha Hospital  Sr.28, Prabhu Complex, Old Mumbai - Pune Hwy, opposite to Republic School, Pune, Maharashtra 412101 Pune   7972700600 ashfak0077@yahoo.co.in  Indu Rao  Kasturba Medical College  Tiger Circle Road, Madhav Nagar, Manipal, Karnataka 576104 Udupi   9592896393 indu.rao@manipal.edu  Lalit Gupta   Lok Nayak Jai Prakash Hospital  Metro Station Central, Jawaharlal Nehru Marg, near Delhi Gate, New Delhi, Delhi 110002 East   9868092739 lalit.doc@gmail.com  Ashish Bhalla  Post Graduate Institute of Medical Education & Research  Madhya Marg, Sector 12, Chandigarh, 160012 Chandigarh   9501767504 bhalla.chd@gmail.com
Details of Ethics Committee Modification(s)	No of Ethics Committees= 7   Name of Committee  Approval Status  All India Institute of Medical Sciences, Raipur, Chhattisgarh  Approved  Christian Hospital, Nabarangpur Odisha  Approved  George Institute for Global Health  Approved  Government Medical College and Hospital, Chandigarh  Approved  Kasturba Medical College and Kasturba Hospital Institutional Ethics Committee  Approved  Lok Nayak Jai Prakash Hospital  Approved  Post Graduate Institute of Medical Education and Research, Chandigarh  Approved
Regulatory Clearance Status from DCGI	Status  Not Applicable
Health Condition / Problems Studied	Health Type  Condition  Patients  Coronavirus as the cause of diseases classified elsewhere
Intervention / Comparator Agent Modification(s)	Type  Name  Details  Comparator Agent  Standard Care   Standard Care   Intervention  Standard Care plus Angiotensin Receptor Blockers (ARB)   Dose: 20 mg to 80 mg. Frequency : Once daily Route of administration: Oral
Inclusion Criteria Modification(s)	Age From  18.00 Year(s) Age To  99.00 Year(s) Gender  Both  Details  Potential participants must meet all of the following: 1. Laboratory-confirmed diagnosis of SARS-CoV-2 infection a. Confirmation through appropriate approved laboratory or Point of Care testing method, including Polymerase Chain Reaction or other public health assay. 2. Age greater than or equal to 18 years 3. Either a. Systolic BP (SBP) greater than or equal to 125mmHg OR b. SBP greater than or equal to 115mmHg and currently treated with a non-RAS inhibitor (RASi) BP-lowering agent that can be ceased 4. Participant and treating staff are willing and able to perform trial procedures. 5. Intended for admission to a participating hospital for management of COVID-19 6. Diagnosis (i.e. date of test result) for SARS-CoV-2 infection must be within 3 days prior to randomisation
ExclusionCriteria	Details  Potential participants must not meet any of the following: 1. Currently treated with an ACEI, ARB 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. Estimated Glomerular Filtration Rate (eGFR) less than 30ml/min/1.73m2 or no eGFR testing within the last 3 months, or 4. Known symptomatic postural hypotension 5. Known biliary obstruction, known severe hepatic impairment (Child-Pugh-Turcotte score 10-15) 6. Intolerance of ARB 7. Women <51 years who are pregnant, have a positive bHCG or are currently breastfeeding 8. 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
Method of Generating Random Sequence	Computer generated randomization
Method of Concealment	Centralized
Blinding/Masking	Open Label
Primary Outcome	Outcome  TimePoints  The primary endpoint is a 7-point NIH Coronavirus Disease 2019 (COVID-19) score, a modified version of the 9-point score developed by the WHO for COVID-19 trials.   The ordinal scale is an assessment of the clinical status of the participant at the first assessment for the day, measured at Day 28.
Secondary Outcome	Outcome  TimePoints  7-point ordinal scale score  At Day 15  Admission to ICU   Between baseline and Day 28 Between baseline and Day 90   AKI, based on Kidney Disease Improving Global Outcomes definition  At Day 28  Dialysis requirement  At Day 28  Hyperkalaemia, defined as more than 6.0mmoL/L   At Day 28  Hypotension requiring vasopressors  Between baseline and Day 28  Length of stay in ICU  To Day 90  Mortality   At Day 28  Number of dialysis days  Between baseline and Day 28  Number of hospitalisation days  Between baseline and Day 28 Between baseline and Day 90  Number of ventilator-free days   Between baseline and Day 28  Oxygen (O2) saturation/Fractional inh-O2   At Day 8 and Day 15  Respiratory failure   At Day 28
Target Sample Size	Total Sample Size="605" Sample Size from India="605"
Phase of Trial	Phase 3
Date of First Enrollment (India) Modification(s)	01/08/2020
Date of First Enrollment (Global)	No Date Specified
Estimated Duration of Trial	Years="0" Months="9" Days="0"
Recruitment Status of Trial (Global) Modification(s)	Completed
Recruitment Status of Trial (India)	Completed
Publication Details Modification(s)	Jardine MJ, Kotwal SS, Bassi A, Hockham C, Jones M, Wilcox A, Pollock C, Burrell LM, McGree J, Rathore V, Jenkins CR. Angiotensin receptor blockers for the treatment of covid-19: pragmatic, adaptive, multicentre, phase 3, randomised controlled trial. bmj. 2022 Nov 16;379. Hockham, C., Kotwal, S., Wilcox, A. et al. Protocol for the Controlled evaLuation of Angiotensin Receptor blockers for COVID-19 respIraTorY disease (CLARITY): a randomised controlled trial. Trials 22, 573 (2021). Controlled evaLuation of Angiotensin Receptor Blockers for COVID-19 respIraTorY disease (CLARITY): Statistical analysis plan for a randomised controlled Bayesian adaptive sample size trial.
Brief Summary	Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel virus that can cause severe infection in the airways (COVID-19). COVID-19 was first described in China in December 2019. With almost 5 million cases globally till date, modeling has predicted up to 3 million cases in India with peaks between July, August and September. The COVID-19 virus can cause a respiratory infection. Its symptoms include fever, coughing, and sore throat. Most people with COVID-19 only have a mild illness, however, in some cases, the illness can be more severe and include symptoms like difficulty breathing. There is no proven treatment for COVID-19 but medical care can manage most of the symptoms while your body fights the infection. Angiotensin Receptor Blockers (ARBs) are a group of medications that have been widely used for over 20 years in India. They are an existing medication used to treat conditions including high blood pressure, kidney disease and heart disease. ARBs may be able to limit the effect of the COVID-19 virus on the body. This is because the COVID19 virus changes normal body processes to infect lung cells and then promotes inflammation in the lung tissue. Both of these negative effects may be partially blocked by ARBs. We hypothesize that treatment with ARBs will be beneficial in attenuating the effect of COVID-19. Many people are already taking ARBs for other reasons when they get COVID-19. These people appear to do at least as well as people who are not on ARBs. However, it is not known if the ARB directly improves their recovery from COVID-19. This study aims to assess whether ARBs will reduce the severity of infection, in people diagnosed with COVID-19.