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

COVID-19 Clinical Trial

— 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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05122182
• Other study ID #: CTC0312
• Status: Terminated
• Phase: Phase 2
• Start date: January 7, 2022
• Est. completion date: January 28, 2023

Study information

• Verified date: September 2023
• Source: University of Sydney
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 49
• Est. completion date: January 28, 2023
• Est. primary completion date: August 15, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• COVID-19
• SARS-CoV2 Infection

Intervention

Drug:
• Candesartan Cilexetil
Angiotensin Receptor Blocker (ARB)
• Repagermanium
C-C chemokine receptor type 2 (CCR2) antagonist
• Candesartan Placebo
Angiotensin Receptor Blocker (ARB) placebo
• Repagermanium Placebo
C-C chemokine receptor type 2 (CCR2) antagonist placebo

Locations

Country	Name	City	State
India	Jawaharlal Nehru Medical College and Hospital	Aligarh
India	Government Medical College and Hospital	Chandigarh
India	Samishta Hospital and Research Institute	Guntur
India	Maharaja Agrasen Hospital	Jaipur
India	Amrita Institute of Medical Science	Kochi
India	Kasturba Medical College	Mangaluru
India	DM Wayanad Institute of Medical Sciences	Meppadi
India	Sterling Hospital	Nigdi
India	Jivanrekha Multi-Speciality Hospital	Pune
India	All India Institute of Medical Sciences, Raipur	Raipur

Sponsors (2)

Lead Sponsor	Collaborator
University of Sydney	The George Institute for Global Health, India

Country where clinical trial is conducted

India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Incidence of Hypotension	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.	28 days
Other	Incidence of Hyperkalemia	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.	28 days
Other	Incidence of Deranged Liver Function Tests	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.	28 days
Other	Total Serious Adverse Events (SAEs)	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.	28 days
Other	Incidence of hospital readmission	Admission for overnight stay up to day 90 following initial hospital discharge.	90 days
Primary	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.	14 days
Secondary	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.	28 days
Secondary	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.	28 days
Secondary	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.	28 days
Secondary	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.	28 days
Secondary	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.	28 days
Secondary	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.	28 days
Secondary	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.	28 days
Secondary	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.	28 days
Secondary	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.	28 days
Secondary	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.	28 days
Secondary	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.	60 days
Secondary	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.	90 days
Secondary	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.	180 days