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BMJ Open
. 2024 Oct 22;14(10):e081790.
doi: 10.1136/bmjopen-2023-081790. Combination of the chemokine receptor type 2 (CCR2) antagonist DMX-200 and candesartan for COVID-19: a randomised controlled trial
Daniel Vincent O'Hara 1 2 , Abhinav Bassi 3 , Arlen Wilcox 4 , Vivekanand Jha 3 5 6 , Vinay Rathore 7 , Sanjay D'Cruz 8 , Thomas L Snelling 4 , Mark Jones 4 , James Totterdell 9 , Ashpak Bangi 10 , Manish Kumar Jain 11 , Carol Pollock 2 12 13 , Louise Burrell 14 15 , Gregory Fox 16 17 , Cheryl Jones 13 , Sradha Kotwal 18 19 , Sharifah Faridah Syed Omar 20 , Meg Jardine 4 21 ; CLARITY 2.0 trial investigators
Collaborators, Affiliations
Objective: To determine whether a chemokine receptor type 2 antagonist, DMX-200 (repagermanium), in combination with an angiotensin receptor blocker, candesartan, improves clinical outcomes in people with COVID-19.
Design: Prospective, multicentre, double-blind, placebo-controlled trial.
Setting: Ten acute care hospitals in India.
Participants: Adults <65 years old intended for hospital admission with moderate/severe COVID-19 disease (respiratory rate ≥24 breaths per minute or oxygen saturation ≤93% on room air).
Intervention: DMX-200 120 mg two times per day, or placebo, on background of titratable candesartan commencing at 4 mg two times per day, for 28 days.
Main outcome measures: The primary endpoint was COVID-19 disease severity on a modified WHO Clinical Progression Scale (WHO scale) on day 14. Secondary outcomes included the WHO scale at days 28, 60, 90 and 180; intensive care unit (ICU) admission, respiratory failure or death within 28 days; length of hospitalisation; and requirement for ventilatory support or dialysis.
Results: Between December 2021 and August 2022, 518 people were screened, with 49 randomised to DMX-200 or placebo on a background of candesartan. The study was terminated early due to recruitment barriers, including an external requirement to restrict enrolment to adults <65 years old, contributing to a 91% screen failure rate. The median WHO Clinical Progression Scale (WHO scale) score at day 14 for both groups was 1 (IQR 1-1), indicating most participants were discharged with no limitations on activities by this time. Formal comparison was not performed due to the small sample size. One participant receiving DMX-200 died of COVID-19 disease progression. No participants required ICU admission, ventilation or dialysis. Median length of hospitalisation in both groups was 6 days (IQR 6-7 days). WHO scale scores were similar at 28, 60, 90 and 180 days.
Conclusion: Due to recruitment barriers, the study was unable to determine whether DMX-200 improves clinical outcomes in people with COVID-19.
Trial registration number: ClinicalTrials.gov NCT05122182.
Keywords: COVID-19; SARS-CoV-2 infection; randomized controlled trial.
. 2024 Oct 22;14(10):e081790.
doi: 10.1136/bmjopen-2023-081790. Combination of the chemokine receptor type 2 (CCR2) antagonist DMX-200 and candesartan for COVID-19: a randomised controlled trial
Daniel Vincent O'Hara 1 2 , Abhinav Bassi 3 , Arlen Wilcox 4 , Vivekanand Jha 3 5 6 , Vinay Rathore 7 , Sanjay D'Cruz 8 , Thomas L Snelling 4 , Mark Jones 4 , James Totterdell 9 , Ashpak Bangi 10 , Manish Kumar Jain 11 , Carol Pollock 2 12 13 , Louise Burrell 14 15 , Gregory Fox 16 17 , Cheryl Jones 13 , Sradha Kotwal 18 19 , Sharifah Faridah Syed Omar 20 , Meg Jardine 4 21 ; CLARITY 2.0 trial investigators
Collaborators, Affiliations
- PMID: 39438096
- DOI: 10.1136/bmjopen-2023-081790
Objective: To determine whether a chemokine receptor type 2 antagonist, DMX-200 (repagermanium), in combination with an angiotensin receptor blocker, candesartan, improves clinical outcomes in people with COVID-19.
Design: Prospective, multicentre, double-blind, placebo-controlled trial.
Setting: Ten acute care hospitals in India.
Participants: Adults <65 years old intended for hospital admission with moderate/severe COVID-19 disease (respiratory rate ≥24 breaths per minute or oxygen saturation ≤93% on room air).
Intervention: DMX-200 120 mg two times per day, or placebo, on background of titratable candesartan commencing at 4 mg two times per day, for 28 days.
Main outcome measures: The primary endpoint was COVID-19 disease severity on a modified WHO Clinical Progression Scale (WHO scale) on day 14. Secondary outcomes included the WHO scale at days 28, 60, 90 and 180; intensive care unit (ICU) admission, respiratory failure or death within 28 days; length of hospitalisation; and requirement for ventilatory support or dialysis.
Results: Between December 2021 and August 2022, 518 people were screened, with 49 randomised to DMX-200 or placebo on a background of candesartan. The study was terminated early due to recruitment barriers, including an external requirement to restrict enrolment to adults <65 years old, contributing to a 91% screen failure rate. The median WHO Clinical Progression Scale (WHO scale) score at day 14 for both groups was 1 (IQR 1-1), indicating most participants were discharged with no limitations on activities by this time. Formal comparison was not performed due to the small sample size. One participant receiving DMX-200 died of COVID-19 disease progression. No participants required ICU admission, ventilation or dialysis. Median length of hospitalisation in both groups was 6 days (IQR 6-7 days). WHO scale scores were similar at 28, 60, 90 and 180 days.
Conclusion: Due to recruitment barriers, the study was unable to determine whether DMX-200 improves clinical outcomes in people with COVID-19.
Trial registration number: ClinicalTrials.gov NCT05122182.
Keywords: COVID-19; SARS-CoV-2 infection; randomized controlled trial.