As the COVID-19 pandemic continues to challenge healthcare systems worldwide, researchers have been exploring various treatment options to improve patient outcomes. One such potential treatment that garnered interest was intravenous vitamin C. However, two harmonized clinical trials, LOVIT-COVID and REMAP-CAP, revealed that intravenous vitamin C did not significantly increase the number of days patients were free from organ support. These findings highlight the need for clinicians to prioritize evidence-based treatments for COVID-19 patients rather than relying on interventions that may be ineffective or even harmful.
The LOVIT-COVID and REMAP-CAP trials evaluated the effect of intravenous vitamin C on adult patients hospitalized with COVID-19. The trials enrolled a total of 1,568 critically ill patients and 1,022 non-critically ill patients from 90 ICUs and 40 non-ICU hospital sites across four continents. Patients were randomized into vitamin C and control groups.
Among critically ill patients who received vitamin C, the median number of organ-support free days was 7, compared to 10 in the control group. The adjusted odds ratio (OR) was 0.88, indicating minimal difference between the two groups. Similarly, for non-critically ill patients, the median number of organ-support free days was 22 in both the vitamin C and control arms, with an adjusted OR of 0.80.
Survival to hospital discharge rates also showed no significant improvement with vitamin C. In critically ill patients, the survival rate was 61.9% in the vitamin C group compared to 64.6% in the control group. Among non-critically ill patients, survival rates were 85.1% and 86.6%, respectively.
The results of these trials challenge the notion that intravenous vitamin C is an effective treatment for COVID-19. While the possibility of some benefit cannot be entirely ruled out, the findings consistently point towards the ineffectiveness of vitamin C in improving patient outcomes. The posterior probabilities for efficacy of vitamin C therapy were low, ranging from 8.6% to 17.8%, while the probabilities for harm and futility were high, ranging from 82.2% to 99.9%.
Lessons from Previous Studies
Before the COVID-19 pandemic, vitamin C gained attention as a potential treatment for sepsis based on a single-center study in 2017. However, subsequent larger clinical trials did not show any benefits with vitamin C in patients with sepsis. These findings echo the current results from the LOVIT-COVID and REMAP-CAP trials, reinforcing the importance of rigorous research before embracing new treatments.
Clinicians should approach the use of intravenous vitamin C with caution based on the evidence from these trials. The authors of an accompanying editorial emphasized that clinicians should prioritize therapies that have been proven to be beneficial for COVID-19 patients, rather than resorting to interventions that are likely ineffective and potentially harmful.
It is essential to acknowledge the limitations of the LOVIT-COVID and REMAP-CAP trials. The trials combined data from two differently designed studies, potentially introducing heterogeneity. The placebo-controlled LOVIT-COVID trial had fewer patients, and the open-label REMAP-CAP trial posed the risk of differential care. Additionally, certain data were unavailable, such as individual vaccination status, specific vitamin C product received, and baseline vitamin C levels.
The LOVIT-COVID and REMAP-CAP trials provide valuable insights into the effectiveness of intravenous vitamin C for COVID-19 patients. The results demonstrate that, overall, intravenous vitamin C did not significantly increase the number of days free from organ support or improve survival rates. These findings underscore the importance of relying on evidence-based treatments and exercising caution when considering interventions that lack robust clinical support. Future research should continue to explore alternative treatments that have demonstrated efficacy in improving outcomes for COVID-19 patients.
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