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

BMJ Open. 2024 Oct 22;14(10):e081790. 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.

Keywords: COVID-19; SARS-CoV-2 infection; randomized controlled trial.

Publication types

  • Randomized Controlled Trial
  • Multicenter Study

MeSH terms

  • Adult
  • Angiotensin II Type 1 Receptor Blockers / therapeutic use
  • Benzimidazoles* / therapeutic use
  • Biphenyl Compounds* / therapeutic use
  • COVID-19 Drug Treatment*
  • COVID-19* / mortality
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Humans
  • India
  • Male
  • Middle Aged
  • Prospective Studies
  • SARS-CoV-2*
  • Severity of Illness Index
  • Tetrazoles* / therapeutic use
  • Treatment Outcome

Substances

  • Benzimidazoles
  • Biphenyl Compounds
  • Tetrazoles
  • candesartan
  • Angiotensin II Type 1 Receptor Blockers

Associated data

  • ClinicalTrials.gov/NCT05122182