Kumar Vijay, Bhushan Divendu, Supriya Sushmita, Ganapule Avinash Aravind, Lohani Pallavi, Pandey Sanjay, Majhi Pramod Kumar, Anand Utpal, Kumar Ramesh, Bhadani Umesh Kumar
Department of General Medicine, All India Institute of Medical Sciences (AIIMS), Patna, Bihar, India.
Department of CFM, All India Institute of Medical Sciences (AIIMS), Patna, Bihar, India.
J Family Med Prim Care. 2022 Aug;11(8):4758-4765. doi: 10.4103/jfmpc.jfmpc_2437_21. Epub 2022 Aug 30.
To study the efficacy of intravenous vitamin C in management of moderate and severe COVID-19.
To determine the efficacy of intravenous vitamin C in reducing in-hospital mortality in moderate and severe cases of COVID-19.
Parallel, double-blinded randomized controlled trial with placebo. Ethical clearance was obtained from the institutional ethics committee, AIIMS Patna. The trial was registered with the Clinical Trials Registry - India (registration number- CTRI/2020/11/029230.).
A tertiary care centre in Bihar, India.
All patients above the age of 18 years both males and females, admitted in ICU with a diagnosis of moderate and severe COVID-19 (on the basis of a positive reverse transcriptase polymerase chain reaction (RT-PCR) report) at our facility during the study period (01/10/2020-31/12/2020) not having any of the exclusion criteria.
The patients in the intervention arm were given 1 gram (2 ampoules of 2 ml each containing 500 mg of vitamin C mixed in 100 ml normal saline) intravenous vitamin C 8 hourly for four days. The patients in the placebo arm received similar looking ampoules (2 ampoules of 2 ml sterile water for injection mixed in 100 ml normal saline) intravenously 8 hourly for four days. The rest of the treatment was given as per the standard operating procedure (SOP) of the institute with adjustments as per treating team's judgement.
Primary outcome was reduction in in-hospital mortality. Secondary outcomes were improvement in qSOFA score, pO2/fiO2 ratio, fall in inflammatory markers, need for mechanical ventilation and vasopressors.
Regarding primary outcome, 10 (33.3%) patients died in intervention group compared to 13 (43.3%) in placebo. Worth noting from baseline characteristics is that 86.7% in intervention arm were of severe category compared to 66.7% severe category patients in placebo group. Though number of severe cases were more in intervention arm there has been comparatively less mortality in this group. Regarding secondary outcomes, amongst 30 patients in vitamin C group, 11 (36.7%) required invasive mechanical ventilation compared to 14 (46.7%) out of 30 in placebo group but the difference was not statistically significant. Although there were a greater number of moderate cases in placebo group, invasive ventilation requirement (and NIV requirement) was more in this group, thus it could be considered that vitamin C might have a role in reducing the severity of disease. The need for vasopressor therapy was higher in intervention arm 33.3% compared to 26.7% in placebo but not significant statistically. The secondary outcomes of the study such as improvement in organ failure score (qSOFA Score), fall in level of inflammatory markers, improvement in respiratory index (pO2/fiO2 ratio), need for mechanical ventilation and need for vasopressors also shown encouraging results but not up to the statistically significant level due to moderate dosage of the drug and small sample size.
In the current study, by the observations and results of the double-blind placebo controlled randomised trial, we concluded that as the primary outcome of the study, there was reduction in In-hospital mortality and need for mechanical ventilation in the vitamin C intervention group compared to placebo, although these results did not reach statistical significance due to small sample size and use of moderate dose of IV vitamin C. The secondary outcomes of the study such as improvement in organ failure score (qSOFA Score), fall in level of inflammatory markers, improvement in respiratory index (pO2/fiO2 ratio), need for mechanical ventilation and need for vasopressors also shown encouraging results but not up to the statistically significant level due to moderate dosage of the drug and small sample size. In summary, high dose of intravenous vitamin C may reduce inflammatory reaction, improve oxygen support status, and reduce mortality in COVID-19 patients, without adverse events. High dose intravenous vitamin C may be a promising therapy for patients of moderate to severe COVID-19.
研究静脉注射维生素C治疗中度和重度新型冠状病毒肺炎（COVID-19）的疗效。
确定静脉注射维生素C对降低中度和重度COVID-19患者院内死亡率的疗效。
平行、双盲、随机对照安慰剂试验。获得了印度巴特那全印医学科学研究所机构伦理委员会的伦理批准。该试验已在印度临床试验注册中心注册（注册号-CTRI/2020/11/029230）。
印度比哈尔邦的一家三级医疗中心。
在研究期间（2020年10月1日至2020年12月31日），所有18岁以上的男性和女性患者，因中度和重度COVID-19诊断（基于逆转录酶聚合酶链反应（RT-PCR）报告阳性）入住我院重症监护病房，且无任何排除标准。
干预组患者每8小时静脉注射1克维生素C（2支2毫升的安瓿，每支含维生素C 500毫克，溶于100毫升生理盐水中），共4天。安慰剂组患者每8小时静脉注射外观相似的安瓿（2支2毫升注射用水，溶于100毫升生理盐水中），共4天。其余治疗按照该机构的标准操作程序（SOP）进行，并根据治疗团队的判断进行调整。
主要结局是降低院内死亡率。次要结局包括快速序贯器官衰竭评分（qSOFA）改善、动脉血氧分压/吸入氧浓度（pO2/fiO2）比值改善、炎症标志物下降、机械通气需求和血管活性药物需求。
关于主要结局，干预组有10例（33.3%）患者死亡，而安慰剂组有13例（43.3%）。从基线特征值得注意的是，干预组86.7%为重症患者，而安慰剂组为66.7%。尽管干预组重症病例数更多，但该组死亡率相对较低。关于次要结局，维生素C组中的30例患者中有11例（36.7%）需要有创机械通气，而安慰剂组中的30例患者中有14例（46.7%）需要，但差异无统计学意义。尽管安慰剂组中度病例数更多，但该组有创通气需求（和无创通气需求）更高，因此可以认为维生素C可能在降低疾病严重程度方面发挥作用。干预组血管活性药物治疗需求为33.3%，高于安慰剂组的26.7%，但差异无统计学意义。该研究的次要结局，如器官衰竭评分（qSOFA评分）改善、炎症标志物水平下降、呼吸指数（pO2/fiO2比值）改善、机械通气需求和血管活性药物需求也显示出令人鼓舞的结果，但由于药物剂量适中且样本量小，未达到统计学显著水平。
在本研究中，通过双盲安慰剂对照随机试验的观察和结果，我们得出结论，作为研究的主要结局，与安慰剂相比，维生素C干预组的院内死亡率和机械通气需求有所降低，尽管由于样本量小和静脉注射维生素C剂量适中，这些结果未达到统计学显著水平。该研究的次要结局，如器官衰竭评分（qSOFA评分）改善、炎症标志物水平下降、呼吸指数（pO2/fiO2比值）改善、机械通气需求和血管活性药物需求也显示出令人鼓舞的结果，但由于药物剂量适中且样本量小，未达到统计学显著水平。总之，高剂量静脉注射维生素C可减轻炎症反应，改善氧供状态，降低COVID-19患者死亡率，且无不良事件。高剂量静脉注射维生素C可能是治疗中度至重度COVID-19患者的一种有前景的疗法。
