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Combination of the chemokine receptor type 2 (CCR2) antagonist DMX-200 and candesartan for COVID-19: a randomised controlled trial

O'Hara DV 1 , Bassi A 2 , Wilcox A 3 , Jha V 2 , Rathore V 4 , D'Cruz S 5 Show all authors , Snelling TL 3 , Jones M 3 , Totterdell J 6 , Bangi A 7 , Jain MK 8 , Pollock C 9 , Burrell L 10 , Fox G 11 , Jones C 12 , Kotwal S 13 , Faridah Syed Omar S 14 , Jardine M 3 , CLARITY 2.0 trial investigators

Affiliations 

  • 1 NHMRC Clinical Trials Centre, Camperdown, New South Wales, Australia daniel.ohara@sydney.edu.au
  • 2 The George Institute for Global Health India, New Delhi, Delhi, India
  • 3 NHMRC Clinical Trials Centre, Camperdown, New South Wales, Australia
  • 4 All India Institute of Medical Sciences, Raipur, India
  • 5 Government Medical College and Hospital, Chandigarh, India
  • 6 School of Public Health, The University of Sydney, Camperdown, New South Wales, Australia
  • 7 Jivanrekha Multispecialty Hospital, Pune, India
  • 8 Maharaja Agrasen Superspecialty Hospital, Jaipur, India
  • 9 Department of Renal Medicine, Royal North Shore Hospital, St Leonards, New South Wales, Australia
  • 10 Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia
  • 11 Central Clinical School, The University of Sydney, Camperdown, New South Wales, Australia
  • 12 Sydney Medical School, The University of Sydney, Camperdown, New South Wales, Australia
  • 13 Renal and Metabolic Division, George Institute for Global Health, Sydney, New South Wales, Australia
  • 14 Department of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia
BMJ Open, 2024 Oct 22;14(10):e081790.
PMID: 39438096 DOI: 10.1136/bmjopen-2023-081790

Abstract

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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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