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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)

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ClinicalTrials.gov Identifier: NCT05122182
Recruitment Status : Recruiting
First Posted : November 16, 2021
Last Update Posted : March 29, 2022
Sponsor:
Collaborator:
The George Institute for Global Health, India
Information provided by (Responsible Party):
University of Sydney

Study Description
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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.

Condition or disease Intervention/treatment Phase
COVID-19 SARS-CoV2 Infection Drug: Candesartan Cilexetil Drug: Repagermanium Drug: Candesartan Placebo Drug: Repagermanium Placebo Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 600 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : January 7, 2022
Estimated Primary Completion Date : July 14, 2022
Estimated Study Completion Date : December 29, 2022

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Interventional Arm
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.
 Drug: Candesartan Cilexetil
Angiotensin Receptor Blocker (ARB)

Drug: Repagermanium
C-C chemokine receptor type 2 (CCR2) antagonist
Other Name: DMX-200
Placebo Comparator: Control Arm #1
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.
 Drug: Candesartan Cilexetil
Angiotensin Receptor Blocker (ARB)

Drug: Repagermanium Placebo
C-C chemokine receptor type 2 (CCR2) antagonist placebo
Placebo Comparator: Control Arm #2
Titratable matched placebo candesartan one tablet twice daily + matched placebo repagermanium one capsule twice daily. Treatment will continue for 28 days.
 Drug: Candesartan Placebo
Angiotensin Receptor Blocker (ARB) placebo

Drug: Repagermanium Placebo
C-C chemokine receptor type 2 (CCR2) antagonist placebo


Outcome Measures
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Primary Outcome Measures :
  1. Clinical Health Score at day 14 [ Time Frame: 14 days ]

    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:

    1. Not hospitalised, no limitations on activities.
    2. Not hospitalised, limitation on activities.
    3. Hospitalised, not requiring supplemental oxygen.
    4. Hospitalised, requiring supplemental oxygen by mask or nasal prongs.
    5. Hospitalised, on non-invasive ventilation or high-flow oxygen devices.
    6. Hospitalised, requiring intubation and mechanical ventilation.
    7. Hospitalised, on invasive mechanical ventilation and additional organ support (ECMO).
    8. Death.


Secondary Outcome Measures :
  1. Clinical Health Score at day 28 [ Time Frame: 28 days ]

    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:

    1. Not hospitalised, no limitations on activities.
    2. Not hospitalised, limitation on activities.
    3. Hospitalised, not requiring supplemental oxygen.
    4. Hospitalised, requiring supplemental oxygen by mask or nasal prongs.
    5. Hospitalised, on non-invasive ventilation or high-flow oxygen devices.
    6. Hospitalised, requiring intubation and mechanical ventilation.
    7. Hospitalised, on invasive mechanical ventilation and additional organ support (ECMO).
    8. Death.

  2. ICU admission [ Time Frame: 28 days ]
    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.

  3. Death [ Time Frame: 28 days ]
    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.

  4. Time to death [ Time Frame: 28 days ]
    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.

  5. Acute Kidney Injury [ Time Frame: 28 days ]
    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.

  6. Respiratory Failure [ Time Frame: 28 days ]
    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.

  7. Length of hospital admission [ Time Frame: 28 days ]
    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.

  8. Length of ICU Admission [ Time Frame: 28 days ]
    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.

  9. Requirement of ventilatory support [ Time Frame: 28 days ]
    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.

  10. Requirement of dialysis [ Time Frame: 28 days ]
    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.

  11. Clinical Health Score at day 60 [ Time Frame: 60 days ]

    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:

    1. Not hospitalised, no limitations on activities.
    2. Not hospitalised, limitation on activities.
    3. Hospitalised, not requiring supplemental oxygen.
    4. Hospitalised, requiring supplemental oxygen by mask or nasal prongs.
    5. Hospitalised, on non-invasive ventilation or high-flow oxygen devices.
    6. Hospitalised, requiring intubation and mechanical ventilation.
    7. Hospitalised, on invasive mechanical ventilation and additional organ support (ECMO).
    8. Death.

  12. Clinical Health Score at day 90 [ Time Frame: 90 days ]

    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:

    1. Not hospitalised, no limitations on activities.
    2. Not hospitalised, limitation on activities.
    3. Hospitalised, not requiring supplemental oxygen.
    4. Hospitalised, requiring supplemental oxygen by mask or nasal prongs.
    5. Hospitalised, on non-invasive ventilation or high-flow oxygen devices.
    6. Hospitalised, requiring intubation and mechanical ventilation.
    7. Hospitalised, on invasive mechanical ventilation and additional organ support (ECMO).
    8. Death.

  13. Clinical Health Score at day 180 [ Time Frame: 180 days ]

    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:

    1. Not hospitalised, no limitations on activities.
    2. Not hospitalised, limitation on activities.
    3. Hospitalised, not requiring supplemental oxygen.
    4. Hospitalised, requiring supplemental oxygen by mask or nasal prongs.
    5. Hospitalised, on non-invasive ventilation or high-flow oxygen devices.
    6. Hospitalised, requiring intubation and mechanical ventilation.
    7. Hospitalised, on invasive mechanical ventilation and additional organ support (ECMO).
    8. Death.


Other Outcome Measures:
  1. Incidence of Hypotension [ Time Frame: 28 days ]
    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.

  2. Incidence of Hyperkalemia [ Time Frame: 28 days ]
    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.

  3. Incidence of Deranged Liver Function Tests [ Time Frame: 28 days ]
    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.

  4. Total Serious Adverse Events (SAEs) [ Time Frame: 28 days ]
    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.

  5. Incidence of hospital readmission [ Time Frame: 90 days ]
    Admission for overnight stay up to day 90 following initial hospital discharge.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05122182


Contacts
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Contact: Katrina Diamante +612 9562 5000 Clarity2.study@sydney.edu.au

Locations
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India
Samishta Hospital and Research Institute Recruiting
Guntur, India
Contact: Satish Babu Podili         
Maharaja Agrasen Hospital Recruiting
Jaipur, India
Contact: Manish Kumar Jain         
Kasturba Medical College Recruiting
Mangaluru, India
Contact: Cynthia Amrutha         
Jivanrekha Multi-Speciality Hospital Recruiting
Pune, India
Contact: Yasmeen Shaikh         
All India Institute of Medical Sciences, Raipur Recruiting
Raipur, India
Contact: Vinay Rathore         
Sponsors and Collaborators
University of Sydney
The George Institute for Global Health, India
Investigators
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Study Chair: Meg Jardine NHMRC Clinical Trials Centre, The University of Sydney
Study Chair: Vivekanand Jha The George Institute for Global Health, India
More Information
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Responsible Party: University of Sydney
ClinicalTrials.gov Identifier: NCT05122182    
Other Study ID Numbers: CTC0312
First Posted: November 16, 2021    Key Record Dates
Last Update Posted: March 29, 2022
Last Verified: March 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University of Sydney:
COVID-19
SARS-CoV2
Angiotensin Receptor Blocker (ARB)
C-C chemokine receptor type 2 (CCR2) antagonist
Additional relevant MeSH terms:
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COVID-19
Respiratory Tract Infections
Infections
Pneumonia, Viral
Pneumonia
Virus Diseases
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases
 Proxigermanium
Candesartan
Candesartan cilexetil
Antihypertensive Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Interferon Inducers
Immunologic Factors
Physiological Effects of Drugs