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Research
Pilot Trial of High-dose vitamin C in critically ill COVID-19 patients
Zhi-Yong Peng
Wuhan University Zhongnan Hospital
Corresponding Author
ORCiD: https://orcid.org/0000-0002-3873-9607
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: No specific medication has been proven effective for the treatment of patients with severe coronavirus disease 2019 (COVID-19). Here, we tested whether high-dose vitamin C infusion was effective for severe COVID-19.
Methods: This randomized, controlled, clinical trial was performed at 3 hospitals in Hubei, China. Patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the ICU were randomly assigned in as 1:1 ratio to either the high-dose intravenous vitamin C (HDIVC) or the placebo. HDIVC group received 12 g of vitamin C/50 ml every 12 hours for 7 days at a rate of 12 ml/hour, and the placebo group received bacteriostatic water for injection in the same way. The primary outcome was invasive mechanical ventilation-free days in 28 days(IMVFD28). Secondary outcomes were 28-day mortality, organ failure, and inflammation progression.
Results: Only fifty-six critical COVID-19 patients were ultimately recruited due to the early control of the outbreak. There was no difference in IMVFD28 between two groups. During the 7-day treatment period, patients in the HDIVC group had a steady rise in the PaO2/FiO2 (day 7: 229 vs. 151 mmHg, 95% CI 33 to 122, P=0.01). Patients with SOFA scores ≥3 in the HDIVC group exhibited a trend of reduction in 28-day mortality (P=0.06) in univariate survival analysis. IL-6 in the HDIVC) group was lower than that in the placebo group (19.42 vs. 158.00; 95% CI -301.72 to -29.79; P=0.04) on day 7.
Conclusion: This pilot trial showed that HDIVC might show a potential signal of benefit for critically ill patients with COVID-19, improving oxygenation even though it failed to improve IMVFD28.
Clinicaltrial.gov identifer and date: NCT04264533. Registered February 14 2020.
Keywords
High dose intravenous vitamin C, Coronavirus disease 2019, Severe Acute Respiratory Syndrome Coronavirus 2
Figure 1
Figure 2
Figure 3
Figure 4
Darshan
commented on 12 October, 2020
Saving life is much more meaningful and critical than quality assessment of a clinical trial.
david austin
commented on 14 October, 2020
Mortality is a "categorical variable", in fact it is the worst case categorical variable because it is boolean (patient is either dead or alive) so requires extremely high sample size to be statistically significant. STOP USING IT. Stop even discussing it with such small populations! (dumb tweets). It's shouldn't even be a secondary measure if the population is too small, which these are. However, continuous variables on the other hand do NOT require large sample sizes, so they are ideal, additionally if they are absolutely predictive of patient recovery in the pathology of the disease then they should be the primary outcome measures. Thankfully low SOFA scores and low inflammatory markers like IL-6 are both continuous AND essential to the pathology of a recovering covid19 patient, and in this study they are both profoundly improved for Vit C group and profoundly significant from a statistical standpoint. More so than ANY OTHER TREATMENT TO DATE. The improvements are better than HCQ by far, better than Remdesivir by far, better than dexamethasone by far, and better than observed in antibody treatments. By far. And no, you don't need multiple RCT's because these findings (SOFA and IL-6) are so significant, and validations of these findings have been repeated again and again in similar RCT's also with statistical significance. Every study so far (and there are at least 3) has confirmed this. 3 independently run statistically significant RCTs (regardless how small the sample size is - remember it's all about statistical significance) ... THAT'S ENOUGH. Policy must follow. These numbers (vastly improved SOFA and IL-6) first appeared 9 months ago when Wuhan did the first tests. The fact it isn't the #1 headlines in NYT, WAPO, and every medical journal, is a damning indictment of our medical leadership since we've been CONSISTENTLY seeing these numbers profoundly improved SOFA and IL-6 for IV Vit C (esp with steroid and heparin). Under their leadership all you hear about it is that vitamin C is some sort of scam. Lastly, let talk money: If every COVID19 ARDS patient (only 10% of COVID19 patients) was treated with 12g/daily for 10 days it would have negligible effect on the vitamin C supply, and the vitamin manufacturers wouldn't see much additional profit from this. 12g is a tiny amount.
View 1 reply
Steve Fowkes
commented on 14 October, 2020
To the authors: please redo your two figures regarding mortality. First, the Y-axis lists percent mortality when the numbers are non-percent mortality. Second, you have one death graphed on day 5 for the control group, but the data below the graph shows two deaths. On day 10, they match at four deaths, and on day 15 they match with six deaths. But on day 20, they again disagree, with 10 deaths illustrated and nine deaths listed. The error continues for day 25 with 11 deaths shown and ten deaths listed. The graph itself has a further error in that day 16, 17 and 18 show half a death on the Y-axis. For the HDIVC group, there are additional discrepancies on day 15 (four deaths versus three), and day 20 (four deaths instead of three). I have yet to look so closely at the higher-risk patient data, but please review that for your own satisfaction. I also see that the Y axis seems to be mis-calibrated, showing > 40% mortality in the placebo group when 11 of 29 is only 38% mortality. -- I'd also like to ask if the vitamin C infusions were universally given on days 1-7. Your methods section implies this when you wrote that "treatment was begun" on day one. Yet multiple treatments were listed as part of your hospital protocols, with no specific mention of whether IV vitamin C was included in the "initial" treatment.
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Research
Pilot Trial of High-dose vitamin C in critically ill COVID-19 patients
Zhi-Yong Peng
Wuhan University Zhongnan Hospital
Corresponding Author
ORCiD: https://orcid.org/0000-0002-3873-9607
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 2
Posted 23 Sep, 2020
Community comments: 5
No comments provided
Metrics
Comments: 5
PDF Downloads: ...
HTML Views: ...
Subject Areas
Pulmonology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: No specific medication has been proven effective for the treatment of patients with severe coronavirus disease 2019 (COVID-19). Here, we tested whether high-dose vitamin C infusion was effective for severe COVID-19.
Methods: This randomized, controlled, clinical trial was performed at 3 hospitals in Hubei, China. Patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the ICU were randomly assigned in as 1:1 ratio to either the high-dose intravenous vitamin C (HDIVC) or the placebo. HDIVC group received 12 g of vitamin C/50 ml every 12 hours for 7 days at a rate of 12 ml/hour, and the placebo group received bacteriostatic water for injection in the same way. The primary outcome was invasive mechanical ventilation-free days in 28 days(IMVFD28). Secondary outcomes were 28-day mortality, organ failure, and inflammation progression.
Results: Only fifty-six critical COVID-19 patients were ultimately recruited due to the early control of the outbreak. There was no difference in IMVFD28 between two groups. During the 7-day treatment period, patients in the HDIVC group had a steady rise in the PaO2/FiO2 (day 7: 229 vs. 151 mmHg, 95% CI 33 to 122, P=0.01). Patients with SOFA scores ≥3 in the HDIVC group exhibited a trend of reduction in 28-day mortality (P=0.06) in univariate survival analysis. IL-6 in the HDIVC) group was lower than that in the placebo group (19.42 vs. 158.00; 95% CI -301.72 to -29.79; P=0.04) on day 7.
Conclusion: This pilot trial showed that HDIVC might show a potential signal of benefit for critically ill patients with COVID-19, improving oxygenation even though it failed to improve IMVFD28.
Clinicaltrial.gov identifer and date: NCT04264533. Registered February 14 2020.
Figure 1
Figure 2
Figure 3
Figure 4
Darshan
commented on 12 October, 2020
Saving life is much more meaningful and critical than quality assessment of a clinical trial.
david austin
commented on 14 October, 2020
Mortality is a "categorical variable", in fact it is the worst case categorical variable because it is boolean (patient is either dead or alive) so requires extremely high sample size to be statistically significant. STOP USING IT. Stop even discussing it with such small populations! (dumb tweets). It's shouldn't even be a secondary measure if the population is too small, which these are. However, continuous variables on the other hand do NOT require large sample sizes, so they are ideal, additionally if they are absolutely predictive of patient recovery in the pathology of the disease then they should be the primary outcome measures. Thankfully low SOFA scores and low inflammatory markers like IL-6 are both continuous AND essential to the pathology of a recovering covid19 patient, and in this study they are both profoundly improved for Vit C group and profoundly significant from a statistical standpoint. More so than ANY OTHER TREATMENT TO DATE. The improvements are better than HCQ by far, better than Remdesivir by far, better than dexamethasone by far, and better than observed in antibody treatments. By far. And no, you don't need multiple RCT's because these findings (SOFA and IL-6) are so significant, and validations of these findings have been repeated again and again in similar RCT's also with statistical significance. Every study so far (and there are at least 3) has confirmed this. 3 independently run statistically significant RCTs (regardless how small the sample size is - remember it's all about statistical significance) ... THAT'S ENOUGH. Policy must follow. These numbers (vastly improved SOFA and IL-6) first appeared 9 months ago when Wuhan did the first tests. The fact it isn't the #1 headlines in NYT, WAPO, and every medical journal, is a damning indictment of our medical leadership since we've been CONSISTENTLY seeing these numbers profoundly improved SOFA and IL-6 for IV Vit C (esp with steroid and heparin). Under their leadership all you hear about it is that vitamin C is some sort of scam. Lastly, let talk money: If every COVID19 ARDS patient (only 10% of COVID19 patients) was treated with 12g/daily for 10 days it would have negligible effect on the vitamin C supply, and the vitamin manufacturers wouldn't see much additional profit from this. 12g is a tiny amount.
View 1 reply
Myrtle Miller
replied on 04 January, 2021
If you have a scientific background and are able to see the benefits of intravenous vitamin C at the very least you should be explaining the why to politicians. The vaccine industry is dirty though so would be knowing you could be targeted. Maybe if enough people with scientific backgrounds start commenting on the facebook pages of politicians they might set up clinics.
View 1 reply
david austin
replied on 05 January, 2021
It's useless. Highly respected doctors have testified before the CDC, NIH and FDA, even Congress, for 10 months now ... most recently since August regarding Ivermectin, which has even greater effect than the MATH+ protocol (combined will likely prevent 90% of deaths). All this has had no effect. Congressmen are powerless to do anything about it because so many are owned by the pharma companies who expect to make buku $ on the vaccines, but the larger issue at hand is the complicity of everyone in the gov't, from politicians to CDC employees, and the media, and especially social media administrators to engage in whatever it takes to get people to get the vaccine, and they see this as competition that will hurt those odds. In fact, the doctors doing this research also want 100% vaccination, but they do not see the two (treatment vs. preventive vaccines) as being competition, it isn't a either or, but all the leaders, administrators, and governing bodies of our society do. So it's a media blackout. Post to your congressmen's page, it will be deprioritized by facebook to appear at the bottom, nobody will see it. Post something on twitter, facebook, medium, etc ... it will not appear in results even when you search for it. Twitter just censored a respected peer reviewed medical journal for publishing the results of the latest Ivermectin test. Peer reviewed! Censored!
Steve Fowkes
commented on 14 October, 2020
To the authors: please redo your two figures regarding mortality. First, the Y-axis lists percent mortality when the numbers are non-percent mortality. Second, you have one death graphed on day 5 for the control group, but the data below the graph shows two deaths. On day 10, they match at four deaths, and on day 15 they match with six deaths. But on day 20, they again disagree, with 10 deaths illustrated and nine deaths listed. The error continues for day 25 with 11 deaths shown and ten deaths listed. The graph itself has a further error in that day 16, 17 and 18 show half a death on the Y-axis. For the HDIVC group, there are additional discrepancies on day 15 (four deaths versus three), and day 20 (four deaths instead of three). I have yet to look so closely at the higher-risk patient data, but please review that for your own satisfaction. I also see that the Y axis seems to be mis-calibrated, showing > 40% mortality in the placebo group when 11 of 29 is only 38% mortality. -- I'd also like to ask if the vitamin C infusions were universally given on days 1-7. Your methods section implies this when you wrote that "treatment was begun" on day one. Yet multiple treatments were listed as part of your hospital protocols, with no specific mention of whether IV vitamin C was included in the "initial" treatment.
Myrtle Miller
replied on 04 January, 2021
If you have a scientific background and are able to see the benefits of intravenous vitamin C at the very least you should be explaining the why to politicians. The vaccine industry is dirty though so would be knowing you could be targeted. Maybe if enough people with scientific backgrounds start commenting on the facebook pages of politicians they might set up clinics.
View 1 reply
david austin
replied on 05 January, 2021
It's useless. Highly respected doctors have testified before the CDC, NIH and FDA, even Congress, for 10 months now ... most recently since August regarding Ivermectin, which has even greater effect than the MATH+ protocol (combined will likely prevent 90% of deaths). All this has had no effect. Congressmen are powerless to do anything about it because so many are owned by the pharma companies who expect to make buku $ on the vaccines, but the larger issue at hand is the complicity of everyone in the gov't, from politicians to CDC employees, and the media, and especially social media administrators to engage in whatever it takes to get people to get the vaccine, and they see this as competition that will hurt those odds. In fact, the doctors doing this research also want 100% vaccination, but they do not see the two (treatment vs. preventive vaccines) as being competition, it isn't a either or, but all the leaders, administrators, and governing bodies of our society do. So it's a media blackout. Post to your congressmen's page, it will be deprioritized by facebook to appear at the bottom, nobody will see it. Post something on twitter, facebook, medium, etc ... it will not appear in results even when you search for it. Twitter just censored a respected peer reviewed medical journal for publishing the results of the latest Ivermectin test. Peer reviewed! Censored!