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All Studies   Meta Analysis    Recent:   
0 0.5 1 1.5 2+ Mortality, combined 28% Improvement Relative Risk Mortality, LOVIT-COVID cri.. 28% Mortality, LOVIT-COVID.. 28% Mortality, REMAP-CAP crit.. -16% Mortality, REMAP-CAP n.. -27% Mortality, combined trials.. -6% Mortality, combined tria.. (b) -8% Mortality, combined tria.. (c) -6% Mortality, combined tria.. (d) -6% Ventilation, combined trials.. -35% Ventilation, combined tr.. (b) -69% Vitamin C  LOVIT-COVID  LATE TREATMENT  DB RCT Is late treatment with vitamin C beneficial for COVID-19? Double-blind RCT 1,560 patients in multiple countries Higher ventilation with vitamin C (p=0.038) c19early.org Adhikari et al., JAMA, October 2023 Favors vitamin C Favors control

Intravenous Vitamin C for Patients Hospitalized With COVID-19 Two Harmonized Randomized Clinical Trials

Adhikari et al., JAMA, doi:10.1001/jama.2023.21407, LOVIT-COVID, NCT04401150
Oct 2023  
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Vitamin C for COVID-19
6th treatment shown to reduce risk in September 2020
 
*, now known with p = 0.000000087 from 70 studies, recognized in 11 countries.
No treatment is 100% effective. Protocols combine complementary and synergistic treatments. * >10% efficacy in meta analysis with ≥3 clinical studies.
4,000+ studies for 60+ treatments. c19early.org
Very late stage (APACHE II 8 and 12 for non-critical and critical) RCT with publication delayed over a year showing higher ventilation and no significant difference in mortality with vitamin C.
Authors have combined what was to be two separate trials into one trial, however there are very large differences between the trials. The results for each source trial are shown separately here Adhikari, Adhikari (B).
eTable 15 shows that results in LOVIT-COVID were substantially better than those in REMAP-CAP. eTable 13 shows improved survival for LOVIT-COVID and worse survival for REMAP-CAP (authors provide mortality breakdown only for hospital survival):
LOVIT-COVID shows 85% and 82% probability of superiority of vitamin C (critical and non-critical).
REMAP-CAP shows 12% and 7% probability of superiority of vitamin C.
Notably, LOVIT-COVID patients were blinded, while REMAP-CAP was open-label, introducing additional opportunity for bias on this highly politicized treatment. REMAP-CAP had more patients and dominates the combined results.
eFigure 8b also shows that the REMAP-CAP results were initially positive, switching to negative around September 2021. Authors note that they were unable to explain this reversal. The overall negative result is only due to the larger number of patients in the REMAP-CAP later time period.
Results for intubation are much worse than mortality, with statistically significant higher intubation for the treatment group. Hypothetically, if the actual risk matched other trials (~20% lower risk in meta analysis of 18 RCTs at the time), and there was something causing biased intubation of treatment patients in this mostly open-label trial, we may get the observed results whereby intubation is significantly worse due to the bias, but this has a muted effect on mortality which may reflect the change in risk due to intubation combined with that due to treatment.
Results varied dramatically over time. For example, during 22 Jan ‐ 21 Apr 2021, the probability of superiority for vitamin C was 1.0 for critical and 0.97 for non-critical (eTable 17).
There were dramatic changes in randomization proportions and in overall clinical outcomes over time, leading to potential issues and inaccuracies in the attempted adjustment for confounding by time.
The very long delay between the end of the trial and publication also raises questions.
NCT04401150 (history) (LOVIT-COVID) and NCT02735707 (history) (REMAP-CAP). 50mg/kg vitamin C administered intravenously over 30-60 minutes every 6 hours for 4 days.
Although the 28% lower mortality is not statistically significant, it is consistent with the significant 19% lower mortality [9‑27%] from meta analysis of the 42 mortality results to date.
This is the 20th of 21 COVID-19 RCTs for vitamin C, which collectively show efficacy with p=0.0012.
This is the 67th of 70 COVID-19 controlled studies for vitamin C, which collectively show efficacy with p=0.000000087 (1 in 11 million).
risk of death, 27.8% lower, HR 0.72, p = 0.19, treatment 190, control 194, combined.
risk of death, 27.5% lower, HR 0.72, p = 0.34, treatment 84, control 97, inverted to make HR<1 favor treatment, LOVIT-COVID critical.
risk of death, 28.1% lower, HR 0.72, p = 0.37, treatment 106, control 97, inverted to make HR<1 favor treatment, LOVIT-COVID non-critical.
risk of death, 16.3% higher, HR 1.16, p = 0.22, inverted to make HR<1 favor treatment, REMAP-CAP critical.
risk of death, 26.6% higher, HR 1.27, p = 0.19, inverted to make HR<1 favor treatment, REMAP-CAP non-critical.
risk of death, 6.4% higher, HR 1.06, p = 0.47, treatment 1,032, control 528, inverted to make HR<1 favor treatment, combined trials, critical, day 90.
risk of death, 7.5% higher, HR 1.08, p = 0.56, treatment 454, control 563, inverted to make HR<1 favor treatment, combined trials, non-critical, day 90.
risk of death, 6.4% higher, HR 1.06, p = 0.61, treatment 1,032, control 528, inverted to make HR<1 favor treatment, combined trials, critical, day 28.
risk of death, 6.4% higher, HR 1.06, p = 0.71, treatment 454, control 563, inverted to make HR<1 favor treatment, non-critical, day 28.
risk of mechanical ventilation, 35.1% higher, HR 1.35, p = 0.04, treatment 1,032, control 528, inverted to make HR<1 favor treatment, combined trials, critical.
risk of mechanical ventilation, 69.5% higher, HR 1.69, p = 0.008, treatment 454, control 563, inverted to make HR<1 favor treatment, combined trials, non-critical.
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Adhikari et al., 25 Oct 2023, Double Blind Randomized Controlled Trial, multiple countries, peer-reviewed, 82 authors, trial NCT04401150 (history) (LOVIT-COVID).
This PaperVitamin CAll
Late treatment
is less effective
Please send us corrections, updates, or comments. c19early involves the extraction of 100,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. FLCCC and WCH provide treatment protocols.
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