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Controlled Trial of Angiotensin Receptor Blocker (ARB) & Chemokine Receptor Type 2 (CCR2) Antagonist for the Treatment of COVID-19 (CLARITY 2)

Primary Purpose

COVID-19, SARS-CoV2 Infection

Status
Terminated
Phase
Phase 2
Locations
India
Study Type
Interventional
Intervention
Candesartan Cilexetil
Repagermanium
Candesartan Placebo
Repagermanium Placebo
Sponsored by
University of Sydney
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for COVID-19 focused on measuring COVID-19, SARS-CoV2, Angiotensin Receptor Blocker (ARB), C-C chemokine receptor type 2 (CCR2) antagonist

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Adults aged ≥ 18 years (maximum 65 years old in India).
  2. Laboratory-confirmed diagnosis of SARS-CoV-2 infection within 10 days prior to randomisation. (Confirmation must be through Reverse Transcription Polymerase Chain Reaction [RT-PCR] method)
  3. Intended for hospital admission for management of COVID-19.
  4. Patients with moderate (respiratory rate of ≥ 24/minute or SPO2: 90% to ≤ 93% on room air) or severe (respiratory rate of ≥ 30/minute or SPO2: <90% on room air) COVID-19.
  5. Systolic Blood Pressure (SBP) ≥ 120 mmHg OR SBP ≥ 115 mmHg and currently treated with a non-RAASi BP lowering agent that can be ceased.
  6. Willing and able to comply with all study requirements, including treatment, timing and/or nature of required assessments.
  7. Documented informed consent.

Exclusion Criteria:

  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.
  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.

Sites / Locations

  • Jawaharlal Nehru Medical College and Hospital
  • Government Medical College and Hospital
  • Samishta Hospital and Research Institute
  • Maharaja Agrasen Hospital
  • Amrita Institute of Medical Science
  • Kasturba Medical College
  • DM Wayanad Institute of Medical Sciences
  • Sterling Hospital
  • Jivanrekha Multi-Speciality Hospital
  • All India Institute of Medical Sciences, Raipur

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

Placebo Comparator

Arm Label

Interventional Arm

Control Arm #1

Control Arm #2

Arm Description

Titratable candesartan with commencing dose 4mg tablets twice daily (daily dose 8 mg) + fixed dose repagermanium one x 120mg immediate release capsule twice daily (total daily dose 240mg). Treatment will continue for 28 days.

Titratable candesartan with commencing dose 4mg tablets twice daily (daily dose 8 mg) + matched placebo repagermanium one capsule twice daily. Treatment will continue for 28 days.

Titratable matched placebo candesartan one tablet twice daily + matched placebo repagermanium one capsule twice daily. Treatment will continue for 28 days.

Outcomes

Primary Outcome Measures

Clinical Health Score at day 14
The primary objective is to evaluate the safety and efficacy of dual treatment with repagermanium and candesartan in patients hospitalised with COVID-19 disease, assessed by the Clinical Health Score at day 14, which is determined within an 8-point ordinal scale of health status: Not hospitalised, no limitations on activities. Not hospitalised, limitation on activities. Hospitalised, not requiring supplemental oxygen. Hospitalised, requiring supplemental oxygen by mask or nasal prongs. Hospitalised, on non-invasive ventilation or high-flow oxygen devices. Hospitalised, requiring intubation and mechanical ventilation. Hospitalised, on invasive mechanical ventilation and additional organ support (ECMO). Death.

Secondary Outcome Measures

Clinical Health Score at day 28
The primary objective is to evaluate the safety and efficacy of dual treatment with repagermanium and candesartan in patients hospitalised with COVID-19 disease, assessed by the Clinical Health Score at day 28, which is determined within an 8-point ordinal scale of health status: Not hospitalised, no limitations on activities. Not hospitalised, limitation on activities. Hospitalised, not requiring supplemental oxygen. Hospitalised, requiring supplemental oxygen by mask or nasal prongs. Hospitalised, on non-invasive ventilation or high-flow oxygen devices. Hospitalised, requiring intubation and mechanical ventilation. Hospitalised, on invasive mechanical ventilation and additional organ support (ECMO). Death.
ICU admission
The secondary objectives are to evaluate the safety and efficacy of dual treatment with repagermanium and candesartan in patients hospitalised with COVID-19 disease, assessed by incidence of ICU admission in days 0-28.
Death
The secondary objectives are to evaluate the safety and efficacy of dual treatment with repagermanium and candesartan in patients hospitalised with COVID-19 disease, assessed by incidence of deaths in days 0-28.
Time to death
The secondary objectives are to evaluate the safety and efficacy of dual treatment with repagermanium and candesartan in patients hospitalised with COVID-19 disease, assessed from hospital admission to death.
Acute Kidney Injury
The secondary objectives are to evaluate the safety and efficacy of dual treatment with repagermanium and candesartan in patients hospitalised with COVID-19 disease, assessed by incidence of acute kidney injury in days 0-28.
Respiratory Failure
The secondary objectives are to evaluate the safety and efficacy of dual treatment with repagermanium and candesartan in patients hospitalised with COVID-19 disease, assessed by incidence of respiratory failure in days 0-28.
Length of hospital admission
The secondary objectives are to evaluate the safety and efficacy of dual treatment with repagermanium and candesartan in patients hospitalised with COVID-19 disease, assessed by days of inpatient stay from admission to discharge or death.
Length of ICU Admission
The secondary objectives are to evaluate the safety and efficacy of dual treatment with repagermanium and candesartan in patients hospitalised with COVID-19 disease, assessed by days in ICU from admission to transfer to ward or death.
Requirement of ventilatory support
The secondary objectives are to evaluate the safety and efficacy of dual treatment with repagermanium and candesartan in patients hospitalised with COVID-19 disease, assessed by count of days with ventilation in days 0-28.
Requirement of dialysis
The secondary objectives are to evaluate the safety and efficacy of dual treatment with repagermanium and candesartan in patients hospitalised with COVID-19 disease, assessed by count of days with dialysis in days 0-28.
Clinical Health Score at day 60
The primary objective is to evaluate the safety and efficacy of dual treatment with repagermanium and candesartan in patients hospitalised with COVID-19 disease, assessed by the Clinical Health Score at day 60, which is determined within an 8-point ordinal scale of health status: Not hospitalised, no limitations on activities. Not hospitalised, limitation on activities. Hospitalised, not requiring supplemental oxygen. Hospitalised, requiring supplemental oxygen by mask or nasal prongs. Hospitalised, on non-invasive ventilation or high-flow oxygen devices. Hospitalised, requiring intubation and mechanical ventilation. Hospitalised, on invasive mechanical ventilation and additional organ support (ECMO). Death.
Clinical Health Score at day 90
The primary objective is to evaluate the safety and efficacy of dual treatment with repagermanium and candesartan in patients hospitalised with COVID-19 disease, assessed by the Clinical Health Score at day 90, which is determined within an 8-point ordinal scale of health status: Not hospitalised, no limitations on activities. Not hospitalised, limitation on activities. Hospitalised, not requiring supplemental oxygen. Hospitalised, requiring supplemental oxygen by mask or nasal prongs. Hospitalised, on non-invasive ventilation or high-flow oxygen devices. Hospitalised, requiring intubation and mechanical ventilation. Hospitalised, on invasive mechanical ventilation and additional organ support (ECMO). Death.
Clinical Health Score at day 180
The primary objective is to evaluate the safety and efficacy of dual treatment with repagermanium and candesartan in patients hospitalised with COVID-19 disease, assessed by the Clinical Health Score at day 180, which is determined within an 8-point ordinal scale of health status: Not hospitalised, no limitations on activities. Not hospitalised, limitation on activities. Hospitalised, not requiring supplemental oxygen. Hospitalised, requiring supplemental oxygen by mask or nasal prongs. Hospitalised, on non-invasive ventilation or high-flow oxygen devices. Hospitalised, requiring intubation and mechanical ventilation. Hospitalised, on invasive mechanical ventilation and additional organ support (ECMO). Death.

Full Information

First Posted
November 14, 2021
Last Updated
September 13, 2023
Sponsor
University of Sydney
Collaborators
The George Institute for Global Health, India
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1. Study Identification

Unique Protocol Identification Number
NCT05122182
Brief Title
Controlled Trial of Angiotensin Receptor Blocker (ARB) & Chemokine Receptor Type 2 (CCR2) Antagonist for the Treatment of COVID-19
Acronym
CLARITY 2
Official Title
An Investigator Initiated, International Multi-Centre, Multi-Arm, Multi-Stage Randomised Double Blind Placebo Controlled Trial of Angiotensin Receptor Blocker (ARB) & Chemokine Receptor Type 2 (CCR2) Antagonist for the Treatment of COVID-19
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Terminated
Why Stopped
Withdrawal of funding support from the trial funder.
Study Start Date
January 7, 2022 (Actual)
Primary Completion Date
August 15, 2022 (Actual)
Study Completion Date
January 28, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Sydney
Collaborators
The George Institute for Global Health, India

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID-19, SARS-CoV2 Infection
Keywords
COVID-19, SARS-CoV2, Angiotensin Receptor Blocker (ARB), C-C chemokine receptor type 2 (CCR2) antagonist

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
49 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Interventional Arm
Arm Type
Experimental
Arm Description
Titratable candesartan with commencing dose 4mg tablets twice daily (daily dose 8 mg) + fixed dose repagermanium one x 120mg immediate release capsule twice daily (total daily dose 240mg). Treatment will continue for 28 days.
Arm Title
Control Arm #1
Arm Type
Placebo Comparator
Arm Description
Titratable candesartan with commencing dose 4mg tablets twice daily (daily dose 8 mg) + matched placebo repagermanium one capsule twice daily. Treatment will continue for 28 days.
Arm Title
Control Arm #2
Arm Type
Placebo Comparator
Arm Description
Titratable matched placebo candesartan one tablet twice daily + matched placebo repagermanium one capsule twice daily. Treatment will continue for 28 days.
Intervention Type
Drug
Intervention Name(s)
Candesartan Cilexetil
Intervention Description
Angiotensin Receptor Blocker (ARB)
Intervention Type
Drug
Intervention Name(s)
Repagermanium
Other Intervention Name(s)
DMX-200
Intervention Description
C-C chemokine receptor type 2 (CCR2) antagonist
Intervention Type
Drug
Intervention Name(s)
Candesartan Placebo
Intervention Description
Angiotensin Receptor Blocker (ARB) placebo
Intervention Type
Drug
Intervention Name(s)
Repagermanium Placebo
Intervention Description
C-C chemokine receptor type 2 (CCR2) antagonist placebo
Primary Outcome Measure Information:
Title
Clinical Health Score at day 14
Description
The primary objective is to evaluate the safety and efficacy of dual treatment with repagermanium and candesartan in patients hospitalised with COVID-19 disease, assessed by the Clinical Health Score at day 14, which is determined within an 8-point ordinal scale of health status: Not hospitalised, no limitations on activities. Not hospitalised, limitation on activities. Hospitalised, not requiring supplemental oxygen. Hospitalised, requiring supplemental oxygen by mask or nasal prongs. Hospitalised, on non-invasive ventilation or high-flow oxygen devices. Hospitalised, requiring intubation and mechanical ventilation. Hospitalised, on invasive mechanical ventilation and additional organ support (ECMO). Death.
Time Frame
14 days
Secondary Outcome Measure Information:
Title
Clinical Health Score at day 28
Description
The primary objective is to evaluate the safety and efficacy of dual treatment with repagermanium and candesartan in patients hospitalised with COVID-19 disease, assessed by the Clinical Health Score at day 28, which is determined within an 8-point ordinal scale of health status: Not hospitalised, no limitations on activities. Not hospitalised, limitation on activities. Hospitalised, not requiring supplemental oxygen. Hospitalised, requiring supplemental oxygen by mask or nasal prongs. Hospitalised, on non-invasive ventilation or high-flow oxygen devices. Hospitalised, requiring intubation and mechanical ventilation. Hospitalised, on invasive mechanical ventilation and additional organ support (ECMO). Death.
Time Frame
28 days
Title
ICU admission
Description
The secondary objectives are to evaluate the safety and efficacy of dual treatment with repagermanium and candesartan in patients hospitalised with COVID-19 disease, assessed by incidence of ICU admission in days 0-28.
Time Frame
28 days
Title
Death
Description
The secondary objectives are to evaluate the safety and efficacy of dual treatment with repagermanium and candesartan in patients hospitalised with COVID-19 disease, assessed by incidence of deaths in days 0-28.
Time Frame
28 days
Title
Time to death
Description
The secondary objectives are to evaluate the safety and efficacy of dual treatment with repagermanium and candesartan in patients hospitalised with COVID-19 disease, assessed from hospital admission to death.
Time Frame
28 days
Title
Acute Kidney Injury
Description
The secondary objectives are to evaluate the safety and efficacy of dual treatment with repagermanium and candesartan in patients hospitalised with COVID-19 disease, assessed by incidence of acute kidney injury in days 0-28.
Time Frame
28 days
Title
Respiratory Failure
Description
The secondary objectives are to evaluate the safety and efficacy of dual treatment with repagermanium and candesartan in patients hospitalised with COVID-19 disease, assessed by incidence of respiratory failure in days 0-28.
Time Frame
28 days
Title
Length of hospital admission
Description
The secondary objectives are to evaluate the safety and efficacy of dual treatment with repagermanium and candesartan in patients hospitalised with COVID-19 disease, assessed by days of inpatient stay from admission to discharge or death.
Time Frame
28 days
Title
Length of ICU Admission
Description
The secondary objectives are to evaluate the safety and efficacy of dual treatment with repagermanium and candesartan in patients hospitalised with COVID-19 disease, assessed by days in ICU from admission to transfer to ward or death.
Time Frame
28 days
Title
Requirement of ventilatory support
Description
The secondary objectives are to evaluate the safety and efficacy of dual treatment with repagermanium and candesartan in patients hospitalised with COVID-19 disease, assessed by count of days with ventilation in days 0-28.
Time Frame
28 days
Title
Requirement of dialysis
Description
The secondary objectives are to evaluate the safety and efficacy of dual treatment with repagermanium and candesartan in patients hospitalised with COVID-19 disease, assessed by count of days with dialysis in days 0-28.
Time Frame
28 days
Title
Clinical Health Score at day 60
Description
The primary objective is to evaluate the safety and efficacy of dual treatment with repagermanium and candesartan in patients hospitalised with COVID-19 disease, assessed by the Clinical Health Score at day 60, which is determined within an 8-point ordinal scale of health status: Not hospitalised, no limitations on activities. Not hospitalised, limitation on activities. Hospitalised, not requiring supplemental oxygen. Hospitalised, requiring supplemental oxygen by mask or nasal prongs. Hospitalised, on non-invasive ventilation or high-flow oxygen devices. Hospitalised, requiring intubation and mechanical ventilation. Hospitalised, on invasive mechanical ventilation and additional organ support (ECMO). Death.
Time Frame
60 days
Title
Clinical Health Score at day 90
Description
The primary objective is to evaluate the safety and efficacy of dual treatment with repagermanium and candesartan in patients hospitalised with COVID-19 disease, assessed by the Clinical Health Score at day 90, which is determined within an 8-point ordinal scale of health status: Not hospitalised, no limitations on activities. Not hospitalised, limitation on activities. Hospitalised, not requiring supplemental oxygen. Hospitalised, requiring supplemental oxygen by mask or nasal prongs. Hospitalised, on non-invasive ventilation or high-flow oxygen devices. Hospitalised, requiring intubation and mechanical ventilation. Hospitalised, on invasive mechanical ventilation and additional organ support (ECMO). Death.
Time Frame
90 days
Title
Clinical Health Score at day 180
Description
The primary objective is to evaluate the safety and efficacy of dual treatment with repagermanium and candesartan in patients hospitalised with COVID-19 disease, assessed by the Clinical Health Score at day 180, which is determined within an 8-point ordinal scale of health status: Not hospitalised, no limitations on activities. Not hospitalised, limitation on activities. Hospitalised, not requiring supplemental oxygen. Hospitalised, requiring supplemental oxygen by mask or nasal prongs. Hospitalised, on non-invasive ventilation or high-flow oxygen devices. Hospitalised, requiring intubation and mechanical ventilation. Hospitalised, on invasive mechanical ventilation and additional organ support (ECMO). Death.
Time Frame
180 days
Other Pre-specified Outcome Measures:
Title
Incidence of Hypotension
Description
The specific safety objectives are to evaluate the safety of dual treatment with repagermanium and candesartan in patients hospitalised with COVID-19 disease, assessed by incidence of hypotension in days 0-28.
Time Frame
28 days
Title
Incidence of Hyperkalemia
Description
The specific safety objectives are to evaluate the safety of dual treatment with repagermanium and candesartan in patients hospitalised with COVID-19 disease, assessed by incidence of hyperkalemia in days 0-28.
Time Frame
28 days
Title
Incidence of Deranged Liver Function Tests
Description
The specific safety objectives are to evaluate the safety of dual treatment with repagermanium and candesartan in patients hospitalised with COVID-19 disease, assessed by incidence of deranged liver function tests in days 0-28.
Time Frame
28 days
Title
Total Serious Adverse Events (SAEs)
Description
The specific safety objectives are to evaluate the safety of dual treatment with repagermanium and candesartan in patients hospitalised with COVID-19 disease, assessed by total number of SAEs in days 0-28.
Time Frame
28 days
Title
Incidence of hospital readmission
Description
Admission for overnight stay up to day 90 following initial hospital discharge.
Time Frame
90 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Adults aged ≥ 18 years (maximum 65 years old in India). Laboratory-confirmed diagnosis of SARS-CoV-2 infection within 10 days prior to randomisation. (Confirmation must be through Reverse Transcription Polymerase Chain Reaction [RT-PCR] method) Intended for hospital admission for management of COVID-19. Patients with moderate (respiratory rate of ≥ 24/minute or SPO2: 90% to ≤ 93% on room air) or severe (respiratory rate of ≥ 30/minute or SPO2: <90% on room air) COVID-19. Systolic Blood Pressure (SBP) ≥ 120 mmHg OR SBP ≥ 115 mmHg and currently treated with a non-RAASi BP lowering agent that can be ceased. Willing and able to comply with all study requirements, including treatment, timing and/or nature of required assessments. Documented informed consent. Exclusion Criteria: Currently treated with an ACEi, ARB or aldosterone antagonist, aliskiren, or ARNi Intolerance of ARBs Serum potassium >5.5 mmol/L An estimated Glomerular Filtration Rate (eGFR) <30ml/min/1.732m Known biliary obstruction, known severe hepatic impairment (Child-Pugh-Turcotte score 10-15) Pregnancy, lactation, or inadequate contraception. Participation in a study of a novel investigational product within 28 days prior to randomisation. Plans to participate in another study of a novel investigational product during this study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Meg Jardine
Organizational Affiliation
NHMRC Clinical Trials Centre, The University of Sydney
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Vivekanand Jha
Organizational Affiliation
The George Institute for Global Health, India
Official's Role
Study Chair
Facility Information:
Facility Name
Jawaharlal Nehru Medical College and Hospital
City
Aligarh
Country
India
Facility Name
Government Medical College and Hospital
City
Chandigarh
Country
India
Facility Name
Samishta Hospital and Research Institute
City
Guntur
Country
India
Facility Name
Maharaja Agrasen Hospital
City
Jaipur
Country
India
Facility Name
Amrita Institute of Medical Science
City
Kochi
Country
India
Facility Name
Kasturba Medical College
City
Mangaluru
Country
India
Facility Name
DM Wayanad Institute of Medical Sciences
City
Meppadi
Country
India
Facility Name
Sterling Hospital
City
Nigdi
Country
India
Facility Name
Jivanrekha Multi-Speciality Hospital
City
Pune
Country
India
Facility Name
All India Institute of Medical Sciences, Raipur
City
Raipur
Country
India

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
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.
IPD Sharing Access Criteria
Data will be available after publication for an indefinite time / for a finite time (specify dates) All data requests will be considered by the primary sponsor on a case-by-case basis. Requests must include a methodologically sound proposal. Specific conditions of use may apply and will be specified in a data sharing agreement that the requester must agree to before access is granted. Access can be requested via the Health Data Australia catalogue
IPD Sharing URL
https://researchdata.edu.au/health/

Learn more about this trial

Controlled Trial of Angiotensin Receptor Blocker (ARB) & Chemokine Receptor Type 2 (CCR2) Antagonist for the Treatment of COVID-19

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