Journal Article

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

Siddiqui, Sabah, Nair, Sivapriya G, Cheema, Yuvraj Singh, Jindal, Atul, Kang, Gagandeep, Pollock, Carol, Totterdell, James, Faridah Syed Omar, Sharifah, Jones, Cheryl, Kanje, Shivam R, Bathla, Nikita, Fox, Gregory, Jain, Manish Kumar, Patel, Suprava, Thwaites, Guy, Xie, Rui, Moni, Merlin, Staplin, Natalie, Nair, Aishwarya, Decaria, Annelise, Jain, Madhavender, Kotwal, Sradha, O'Hara, Daniel Vincent, Snelling, Thomas L, Bassi, Abhinav, Jones, Mark, Sahu, Anjulata, Heritier, Stephane, D'Cruz, Sanjay, Sathish Babu, P., Wilcox, Arlen, Kalyan Chakravarthy, K., Jardine, Meg, Mercade, Gerard Estivill, Bangi, Ashpak, Soni, Kapil, Jha, Vivekanand, Diamante, Katrina, Shaikh, Yasmeen, Vimal, Sanjeev Kumar, Haynes, Richard, Burrell, Louise, Abignano, Nicola, Rathore, Vinay

2024

Overview

ObjectiveTo 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.DesignProspective, multicentre, double-blind, placebo-controlled trial.SettingTen acute care hospitals in India.ParticipantsAdults <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).InterventionDMX-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 measuresThe 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.ResultsBetween 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.ConclusionDue to recruitment barriers, the study was unable to determine whether DMX-200 improves clinical outcomes in people with COVID-19.Trial registration numberClinicalTrials.gov NCT05122182.

• Publisher: British Medical Journal Publishing Group,BMJ Publishing Group LTD,BMJ Publishing Group
• Subject: Adult / Angiotensin II Type 1 Receptor Blockers - therapeutic use / Benzimidazoles - therapeutic use / Biphenyl Compounds - therapeutic use / Blood pressure / Chemokines / COVID-19 / COVID-19 - mortality / COVID-19 Drug Treatment / Double-Blind Method / Drug Therapy, Combination / Female / Humans / India / Infections / Inflammation / Male / Middle Aged / Organometallic Compounds - therapeutic use / Original Research / Oxygen saturation / Pandemics / Pneumonia / Potassium / Prospective Studies / randomized controlled trial / Receptors, CCR2 - antagonists & inhibitors / Respiratory Medicine / SARS-CoV-2 / SARS-CoV-2 infection / Severe acute respiratory syndrome coronavirus 2 / Severity of Illness Index / Statistical analysis / Tetrazoles - therapeutic use / Treatment Outcome