Controlled Trial of Angiotensin Receptor Blocker (ARB) & Chemokine Receptor Type 2 (CCR2) Antagonist for the Treatment of COVID-19
- Conditions
- COVID-19SARS-CoV2 Infection
- Interventions
- Registration Number
- NCT05122182
- Lead Sponsor
- University of Sydney
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 49
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Control Arm #1 Repagermanium Placebo 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. Control Arm #2 Repagermanium Placebo Titratable matched placebo candesartan one tablet twice daily + matched placebo repagermanium one capsule twice daily. Treatment will continue for 28 days. Control Arm #2 Candesartan Placebo Titratable matched placebo candesartan one tablet twice daily + matched placebo repagermanium one capsule twice daily. Treatment will continue for 28 days. Interventional Arm Candesartan Cilexetil 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. Control Arm #1 Candesartan Cilexetil 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. Interventional Arm Repagermanium 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.
- Primary Outcome Measures
Name Time Method Clinical Health Score at day 14 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
Name Time Method ICU admission 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.
Requirement of dialysis 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.
Respiratory Failure 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.
Clinical Health Score at day 90 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.Death 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.
Clinical Health Score at day 28 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.Time to death 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.
Acute Kidney Injury 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.
Length of hospital admission 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.
Length of ICU Admission 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.
Requirement of ventilatory support 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.
Clinical Health Score at day 180 180 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.Clinical Health Score at day 60 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.
Trial Locations
- Locations (10)
DM Wayanad Institute of Medical Sciences
🇮🇳Meppadi, India
Sterling Hospital
🇮🇳Nigdi, India
Jivanrekha Multi-Speciality Hospital
🇮🇳Pune, India
Samishta Hospital and Research Institute
🇮🇳Guntur, India
Amrita Institute of Medical Science
🇮🇳Kochi, India
All India Institute of Medical Sciences, Raipur
🇮🇳Raipur, India
Government Medical College and Hospital
🇮🇳Chandigarh, India
Maharaja Agrasen Hospital
🇮🇳Jaipur, India
Jawaharlal Nehru Medical College and Hospital
🇮🇳Aligarh, India
Kasturba Medical College
🇮🇳Mangaluru, India