Patients hospitalized with COVID-19 at 130 sites on 4 continents received little benefit from intravenous vitamin C, researchers report. The authors concluded that the intervention had a “low probability” of improving a primary composite outcome of organ support–free days and hospital survival.
Two prospectively harmonized randomized clinical trials enrolled critically ill patients receiving organ support in intensive care units at 90 sites and patients who were not critically ill at 40 sites from July 2020 to July 2022. Participants were randomized to receive intravenous vitamin C or control (placebo or no vitamin C) every 6 hours for 96 hours (maximum of 16 doses).
“Enrollment was terminated after statistical triggers for harm and futility were met,” the authors write. “The trials had primary outcome data for 1,568 critically ill patients (1,037 in the vitamin C group and 531 in the control group; median age, 60 years [IQR, 50-70 years]; 35.9% were female) and 1,022 patients who were not critically ill (456 in the vitamin C group and 566 in the control group; median age, 62 years [IQR, 51-72 years]; 39.6% were female). Among critically ill patients, the median number of organ support–free days was 7 (IQR, −1 to 17 days) for the vitamin C group vs 10 (IQR, −1 to 17 days) for the control group (adjusted proportional OR, 0.88 [95% credible interval {CrI}, 0.73 to 1.06]) and the posterior probabilities were 8.6% (efficacy), 91.4% (harm), and 99.9% (futility). Among patients who were not critically ill, the median number of organ support–free days was 22 (IQR, 18 to 22 days) for the vitamin C group vs 22 (IQR, 21 to 22 days) for the control group (adjusted proportional OR, 0.80 [95% CrI, 0.60 to 1.01]) and the posterior probabilities were 2.9% (efficacy), 97.1% (harm), and greater than 99.9% (futility). Among critically ill patients, survival to hospital discharge was 61.9% (642/1,037) for the vitamin C group vs 64.6% (343/531) for the control group (adjusted OR, 0.92 [95% CrI, 0.73 to 1.17]) and the posterior probability was 24.0% for efficacy. Among patients who were not critically ill, survival to hospital discharge was 85.1% (388/456) for the vitamin C group vs 86.6% (490/566) for the control group (adjusted OR, 0.86 [95% CrI, 0.61 to 1.17]) and the posterior probability was 17.8% for efficacy.”
Editorial: “Treatment options for bacterial sepsis differ greatly from those for viral sepsis caused by COVID-19,” editorialists write. “Clinicians have minimal therapeutic options beyond antimicrobial therapy and supportive care in patients with bacterial sepsis. However, in patients hospitalized with COVID-19, there are numerous effective therapeutics that, depending on the stage of the disease, can target either the host response (eg, corticosteroids, baricitinib, tocilizumab, infliximab, abatacept) or the virus (eg, remdesivir). Although the allure of vitamin C may continue to tempt clinicians, the results from the harmonized LOVIT-COVID and REMAP-CAP trials should lead clinicians to use therapies that have been demonstrated to be beneficial in patients with COVID-19 as opposed to one that is almost certainly ineffective and potentially harmful.”