Abstract
Background: At present, no single efficacious therapeutic exists for acute COVID-19 management and a multimodal approach may be necessary. 2-deoxy-D-glucose (2-DG) is a metabolic inhibitor that has been shown to limit multiplication of SARS-CoV-2 in-vitro. We evaluated the efficacy and safety of 2-DG as adjunct to standard care in the treatment of moderate to severe COVID-19 patients.
Methods: We conducted a randomized, open-label, phase II, clinical study to evaluate the efficacy, safety, and tolerability of 2-DG administered as adjunct to standard of care (SOC). A total of 110 patients between the ages of 18 and 65 years with moderate to severe COVID-19 were included. Patients were randomized to receive 63, 90, or 126 mg/kg/day 2-DG in addition to SOC or SOC only. Times to maintaining SpO 2 ≥ 94% on room air, discharge, clinical recovery, vital signs normalisation, improvement by 1 and 2 points on WHO clinical progression scale, negative conversion on RT-PCR, requirement for intensive care, and mortality were analyzed to assess the efficacy.
Results: Patients treated with 90 mg/kg/day 2-DG plus SOC showed better outcomes. Time to maintaining SpO 2 ≥ 94% was significantly shorter in the 2-DG 90 mg compared to SOC (median 2.5 days vs. 5 days, Hazard ratio [95% confidence interval] = 2.3 [1.14, 4.64], p = 0.0201). Times to discharge from isolation ward, to clinical recovery, and to vital signs normalization were significantly shorter for the 2-DG 90 mg group. All three doses of 2-DG were well tolerated. Thirty-three (30.3%) patients reported 65 adverse events and were mostly (86%) mild.
Conclusions: 2-DG 90 mg/kg/day as adjunct to SOC showed clinical benefit over SOC alone in the treatment of moderate to severe COVID-19. The promising trends observed in current phase II study is encouraging for confirmatory evaluation of the efficacy and safety of 2-DG in a larger phase III trial.
Trial registration: CTRI, CTRI/2020/06/025664. Registered 5th June 2020, http://ctri.nic.in/Clinicaltrials/pdf_generate.php?trialid=44369&EncHid=&modid=&compid=%27,%2744369det%27 .
Keywords: 2-deoxy-D-glucose; COVID-19; Randomised clinical trial; SARS-CoV-2.
【저자키워드】 COVID-19, SARS-CoV-2, randomised clinical trial, 2-deoxy-D-glucose, 【초록키워드】 Treatment, SARS-CoV-2, Efficacy, Mortality, Trial, Open-label, intensive care, severe COVID-19, progression, RT-PCR, discharge, clinical recovery, outcomes, Randomized, management, adverse event, Patient, Isolation, Mild, age, Efficacy and safety, WHO, vital sign, moderate, clinical study, Normalisation, 2-DG, dose, In-vitro, Standard of care, Tolerability, standard care, Negative conversion, hazard, clinical benefit, severe COVID-19 patients, acute COVID-19, CTRI, Administered, approach, time, limit, shown, analyzed, evaluate, reported, addition, evaluated, conducted, median, treated, receive, efficacious therapeutic, metabolic inhibitor, significantly shorter, 【제목키워드】 clinical trial, randomised, management, Standard of care,