COVID-19, SARS-CoV2 Infection
Conditions
Keywords
COVID-19, SARS-CoV2, Angiotensin Receptor Blocker (ARB), C-C chemokine receptor type 2 (CCR2) antagonist
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.
Interventions
DRUGCandesartan Cilexetil
Angiotensin Receptor Blocker (ARB)
DRUGRepagermanium
C-C chemokine receptor type 2 (CCR2) antagonist
DRUGCandesartan Placebo
Angiotensin Receptor Blocker (ARB) placebo
DRUGRepagermanium Placebo
C-C chemokine receptor type 2 (CCR2) antagonist placebo
Sponsors
The George Institute
University of Sydney
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Deranged Liver Function Tests | 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. |
| Total Serious Adverse Events (SAEs) | 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. |
| Incidence of hospital readmission | 90 days | Admission for overnight stay up to day 90 following initial hospital discharge. |
| Incidence of Hypotension | 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. |
| Incidence of Hyperkalemia | 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. |
Countries
India
Outcome results
None listed