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CTRI Number  CTRI/2021/10/037468 [Registered on: 22/10/2021] Trial Registered Prospectively
Last Modified On: 05/03/2024
Post Graduate Thesis  No 
Type of Trial  Interventional 
Type of Study   Drug 
Study Design  Randomized, Parallel Group, Placebo Controlled Trial 
Public Title of Study   Role of commonly used blood pressure medications in treatment of COVID-19 (CLARITY 2.0) 
Scientific Title of Study   An Investigator Initiated, International Multi-Centre, Multi-Arm, Multi-Stage Randomised Double Blind Placebo Controlled Trial of Angiotensin Receptor Blocker (ARB) and Chemokine Receptor Type 2 (CCR2) Antagonist for the treatment of COVID-19 
Trial Acronym  CLARITY 2.0 
Secondary IDs if Any  
Secondary ID  Identifier 
NIL  NIL 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Dr Vivekanand Jha 
Designation  Executive Director  
Affiliation  George Institute for Global Health 
Address  308-309 (Room Number), Office of the Executive Director (Department & Division), Third Floor, Elegance Tower, Plot No. 8, Jasola District Centre
308-309 (Room Number), Office of the Executive Director (Department & Division), Third Floor, Elegance Tower, Plot No. 8, Jasola District Centre
South
DELHI
110025
India 
Phone  911141588091  
Fax  911141588090  
Email  vjha@georgeinstitute.org.in  
 
Details of Contact Person
Scientific Query  
Name  Dr Vivekanand Jha 
Designation  Executive Director  
Affiliation  George Institute for Global Health 
Address  308-309 (Room Number), Office of the Executive Director (Department & Division), Third Floor, Elegance Tower, Plot No. 8, Jasola District Centre
308-309 (Room Number), Office of the Executive Director (Department & Division), Third Floor, Elegance Tower, Plot No. 8, Jasola District Centre
South
DELHI
110025
India 
Phone  911141588091  
Fax  911141588090  
Email  vjha@georgeinstitute.org.in  
 
Details of Contact Person
Public Query  
Name  Dr Vivekanand Jha 
Designation  Executive Director  
Affiliation  George Institute for Global Health 
Address  308-309 (Room Number), Office of the Executive Director (Department & Division), Third Floor, Elegance Tower, Plot No. 8, Jasola District Centre
308-309 (Room Number), Office of the Executive Director (Department & Division), Third Floor, Elegance Tower, Plot No. 8, Jasola District Centre
South
DELHI
110025
India 
Phone  911141588091  
Fax  911141588090  
Email  vjha@georgeinstitute.org.in  
 
Source of Monetary or Material Support  
The University of Sydney 
 
Primary Sponsor  
Name  The University of Sydney 
Address  NHMRC Clinical Trials Centre 
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 = 10  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr Vinay Rathore  All India Institute of Medical Sciences  All India institute of medical sciences, Raipur, Gate No 4, D block , Ground floor G.E Road, Tatibandh, 492099 chhattisgarh
Raipur
CHHATTISGARH 		 9914699651

vinayrathoremd@gmail.com 
Merlin Moni  Amrita Institute of Medical Sciences  AIMS Ponekkara PO Kochi 682041
Kozhikode
KERALA 		 9567925019

drmerlin.blessan@gmail.com 
Aneesh Basheer  DM Wayanad Institute of Medical Sciences  Wayanad
Wayanad
KERALA 		 9677154338

basheeraneesh@gmail.com 
Sanjay Dcruz  Government Medical College and Hospital  Sector 32-B, Chandigarh
Chandigarh
CHANDIGARH 		 9646121556

sanjaydcruz@gmch.gov.in 
Syed Haider Mehdi Husaini  Jawaharlal Nehru Medical College and Hospital  Faculty of Medicine, Aligarh Muslim University
Aligarh
UTTAR PRADESH 		 8958786889

dr.haiderhusaini2k@gmail.com 
Dr Ashpak Bangi  Jivanrekha Multispecialty Hospital  Sr No 28, Prabhu Complex,Dehuroad, Pune Sr No 28,Opp. Republic School, Dehuroad, Pune Maharashtra 412101
Pune
MAHARASHTRA 		 7972700600

ashfak0077@yahoo.co.in 
Cynthia Amrutha  Kasturba Medical College  Faculty of Medicine, KMC Manipal, Manipal 576104
Udupi
KARNATAKA 		 7259415415

cynthia.amrutha@manipal.edu 
Dr Manish Kumar Jain  Maharaja Agrasen Multispeciality Hospital  Central Spine, Agrasen Aspatal Marg, Sector 7, Vidyadhar Nagar, Jaipur, Rajasthan 302039
Jaipur
RAJASTHAN 		 7737258659

doctormanishjain2@gmail.com 
Dr Koganti Kalyan Chakravarthy  Samishta Hospital and Research Institute  Donka Road, Opposite 4th Line Arundelpet, Guntur, Andhra Pradesh 522002 India
Guntur
ANDHRA PRADESH 		 9110672821

drkalyanhelp@gmail.com 
Abhishek Karmalkar  Sterling Multispecialty Hospital   Sector No 27, Near Bhel Chowk, Nigdi Pradhikaran, Pune
Pune
MAHARASHTRA 		 9850337271

dr.karmalkar@gmail.com 
 
Details of Ethics Committee
Modification(s)  
No of Ethics Committees= 10  
Name of Committee  Approval Status 
Amrita Institute of Medical Sciences Institutional Ethics Committee  Approved 
Ethical Committee DM WIMS Medical College  Approved 
Instituional Ethics Committee Jawaharlal Nehru Medical College & Hospital Faculty of Medicine  Approved 
Institute Ethics Committee All India Institute of Medical Sciences Raipur Chhattisgarh  Approved 
Institutional Ethics Committee GMCH Chandigarh  Approved 
Institutional Ethics Committee Sterling Multi Specialty Hospital   Approved 
Jivanrekha Hospital Institutional Ethics Committee  Approved 
Kasturba Medical College and Kasturba Hospital Institutional Ethics Committee  Approved 
Maharaja Agrasen Superspeciality Hospital  Approved 
Samishta Hospital and Research Institute  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Approved/Obtained 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  (1) ICD-10 Condition: B972||Coronavirus as the cause of diseases classified elsewhere,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Comparator Agent  Candesartan ARB and placebo repagermanium  Oral candesartan 4mg twice daily for 28 days plus placebo twice daily for 28 days 
Intervention  Dual therapy of candesartan and Repagermanium.  Oral candesartan 4mg twice daily for 28 days + Repagermanium 120mg immediate release capsule twice daily for 28 days 
Comparator Agent  Placebo candesartan ARB plus placebo repagermanium  placebo twice daily for 28 days 
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  99.00 Year(s)
Gender  Both 
Details  1.Adults aged ≥ 18 years
2.Laboratory-confirmed diagnosis of SARS-CoV-2 infection within 10 days prior to randomisation (Confirmation through appropriate approved laboratory or Point of Care testing method, including Polymerase Chain Reaction (PCR) or other public health assay.)
3.Systolic Blood Pressure (SBP) ≥ 120 mmHg OR SBP ≥ 115 mmHg and currently treated with a non-RAASi BP lowering agent that can be ceased.
4.Willing and able to comply with all study requirements, including treatment, timing and/or nature of required assessments.
5.Documented informed consent
 
 
ExclusionCriteria 
Details  1.Currently treated with an ACEi, ARB or aldosterone antagonist, aliskiren, or ARNi
2.Intolerance of ARBs
3.Serum potassium >5.5 mmol/L
4.An estimated Glomerular Filtration Rate (eGFR) <30ml/min/1.732m
5.Known biliary obstruction, known severe hepatic impairment (Child-Pugh-Turcotte score 10-15)
6.Pregnancy, lactation, or inadequate contraception.
o Female participants must be either post-menopausal, infertile or use a reliable means of contraception for at least 60 days after the last dose of investigational product or refrain. Where they are of childbearing potential, female participants must also have a negative pregnancy test result within 7 days prior to registration.
o Male participants must have been surgically sterilised or use a (double if required) barrier method of contraception during the treatment period and for at least 60 days after the last dose of investigational product or refrain from donating sperm during this period.
7.Participation in a study of a novel investigational product within 28 days prior to randomisation.
8.Plans to participate in another study of a novel investigational product during this study.
 
 
Method of Generating Random Sequence   Adaptive randomization, such as minimization 
Method of Concealment   On-site computer system 
Blinding/Masking   Participant and Investigator Blinded 
Primary Outcome  
Outcome  TimePoints 
The primary endpoint is a Clinical Health Score, determined within a 7-point ordinal scale of clinical health status which is a modified version of the 9-point score developed by the WHO for Coronavirus Disease 2019 (COVID-19) trials.  Day 1-14
 
 
Secondary Outcome  
Outcome  TimePoints 
Clinical Health Score  Day 28
Day 60
Day 90
Day 180
 
ICU admission  Day 0-28 
Death  Day 0-28 
Time to death  Between hospital admission and death 
Incidence of Acute Kidney Injury  Day 0-28 
Incidence of Respiratory Failure  Day 0-28 
Length of hospitalisation  From admission to discharge/death 
Length of ICU admission  From ICU admission to discharge to ward/death 
Requirement of ventilatory support  Days 0-28 
Requirement of dialysis  Days 0-28 
 
Target Sample Size
Modification(s)  		 Total Sample Size="80"
Sample Size from India="80" 
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" 
Phase of Trial
Modification(s)  		 Phase 2 
Date of First Enrollment (India)   01/11/2021 
Date of Study Completion (India) Applicable only for Completed/Terminated trials 
Date of First Enrollment (Global)  Date Missing 
Date of Study Completion (Global) Applicable only for Completed/Terminated trials 
Estimated Duration of Trial   Years="1"
Months="6"
Days="0" 
Recruitment Status of Trial (Global)
Modification(s)  		 Not Applicable 
Recruitment Status of Trial (India)  Other (Terminated) 
Publication Details   Not yet 
Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?  

Response - NO
Brief Summary  

The major cause of mortality from COVID-19 has been life-threatening pneumonia and acute respiratory distress syndrome (ARDS). Elevated levels of a number of pro-inflammatory cytokines, including interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1, also known as C-C Motif Chemokine Ligand 2 [CCL2]) have been reported in patients with severe COVID-19, suggesting involvement of a hyper-inflammatory immune response. MCP-1 is a chemokine with a key role in macrophage recruitment and activation and is the natural ligand for Chemokine Receptor Type 2 (CCR2).  The capacity of CCR2 in the setting of COVID-19 has not been tested with most programs testing CCR2 in the setting of chronic disease such as renal disease.

 

Alongside the role of chemokines in inducing the hyperinflammatory response, there is good evidence that the renin-angiotensin system (RAS) may also play a role in the pathophysiology of COVID-19. The RAS is responsible for regulating haemodynamic, inflammatory, and fibrotic processes, and includes two main cross-regulating axes: the vasoconstrictive, pro-inflammatory, pro-fibrotic ACE-Ang II-AT1R axis, and the vasodilatory, anti-inflammatory, anti-fibrotic ACE2-Ang1-7-MasR and ACE2-Ang1-9-AT2R axis. SARS-CoV-2 responsible for COVID-19 appears to bind and downregulate angiotensin converting enzyme type 2 (ACE2).  Animal studies of the related SARS-CoV-1 suggest that this downregulation of ACE2 is sufficient for causing lung pathology and is reversed by treatment with an Angiotensin Receptor Blocker (ARB).  Several randomised controlled trials are underway to assess the effectiveness of ARBs in limiting the severity of COVID-19.

 

CLARITY 2.0 is an investigator-initiated trial that will evaluate the safety and efficacy of dual treatment with repagermanium, a CCR2 antagonist and candesartan, an ARB, in patients hospitalised with COVID-19 disease.


 
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