CEMVIS: Clinical Efficacy of Megadose Vitamin C in Sepsis
Study Details
Study Description
Brief Summary
In this multicenter, randomized, single-blind, placebo-controlled clinical trial. Patients will be randomly assigned to receive Vitamin C or placebo for 4 days or until ICU discharge (whatever come first). The primary outcome is 28-day all-cause mortality.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
Investigational drug: Vitamin C for injection
Study title: Clinical efficacy of megadose vitamin C in sepsis (CEMVIS): A Multicenter, Randomized, Single-blind, Placebo-controlled Clinical Trial
Principal Investigator: Zhanguo Liu, professor, Department of Critical Care Medicine, Zhujiang Hospital, Southern Medical University
Study subjects: Adult septic/septic shock patients with procalcitonin(PCT)≥2ng/ml at recruitment.
Study phase: Investigator Initiated Trial(IIT)
Study objectives: The objective of the study is to determine whether megadose vitamin c, compared to placebo, improve the prognosis of sepsis, including the reduction in mortality, the protection of organ function and reduction of inflammatory response, and to determine the safety of megadose vitamin c in patients with sepsis.
Study design: A Multicenter, Randomized, Single-blind, Placebo-controlled Clinical Trial
Method： Megadose vitamin C group: routine treatment follow the recommendation of the guidelines for sepsis in 2021+ 12 g vitamin C (48 ml) injection every 12 h for 4 days or until ICU discharge (death or transfer from ICU to general ward or discharge), whatever come first. Placebo control group: routine treatment follow the recommendation of the guidelines for sepsis in 2021 + 48ml 5% glucose injection every 12 h for 4 days or until ICU discharge (death or transfer from ICU to general ward or discharge), whatever come first.
Course: 4 days
Sample size: 152
The number of study center: 5
Study center:
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Department of Critical Care Medicine of Zhujiang Hospital,Guangzhou, Guangdong, China
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Department of Critical Care Medicine of The First People's Hospital of Foshan, Foshan, Guangdong, China
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Department of Critical Care Medicine of Dongguan People's Hospital, Dongguan, Guangdong,China
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Department of Critical Care Medicine of Yunfu People' s Hospital, Yunfu, Guangdong, China
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Department of Critical Care Medicine of Zhongshan People's Hospital, Zhongshan, Guangdong, China
Primary endpoint: 28-day all-cause mortality.
Secondary endpoints:
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The state of liver function: the serum level of transaminase(AST、ALT)、total bilirubin at 96 h after randomization
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The state of lung function: oxygenation index(PaO2/FiO2) at 96h after randomization
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The state of kidney function: serum level of Creatinine (Cr)、blood urea nitrogen(BUN)、Cystatin(Cys) at 96 h after randomization
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The state of inflammatory response: the serum level of interleukin-6(IL-6) and C-reactive protein(CRP) at 96 h after randomization.
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The state of infection: the serum level of procalcitonin(PCT) and white blood cell （WBC） at 96 h after randomization.
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The state of circulation system: the serum level of lactate at 96 h after randomization
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Organ dysfunction assessed by Sequential Organ Failure Assessment (SOFA) score at 96 h after randomization
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The duration of successful cessation of supportive therapies for organ dysfunction including vasoactive agents, mechanical ventilation.
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The duration of continuous renal replacement therapy(CRRT)
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The length of stay in ICU
Safety endpoints：
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adverse events
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Serious adverse events
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Megadose vitamin C group 12 g vitamin C (48 ml) will intravenously injected by a infusion pump every 12 h for 4 days or until ICU discharge |
Drug: Vitamin C
12 g vitamin C (48 ml) will be intravenously injected by a infusion pump every 12 h for 4 days or at ICU discharge
|
| Placebo Comparator: Placebo group 5% glucose solution 48 ml every 12 h for 4 days or until ICU discharge. |
Drug: 5% glucose injection
5% glucose solution 48 ml every 12 h for 4 days or at ICU discharge.
|
Outcome Measures
Primary Outcome Measures
- 28-day all-cause mortality [The outcome will be assessed at the 28 day after enrollment]
All-cause mortality from the enrollment to the 28th days
Secondary Outcome Measures
- liver function(1) [The outcome will be assessed at the 0, 1 ,2 ,4 day after enrollment]
the serum level of Alanine transaminase(ALT)
- liver function(2) [The outcome will be assessed at the 0, 1 ,2 ,4 day after enrollment]
the serum level of Aspartate transaminase (AST)
- liver function(3) [The outcome will be assessed at the 0, 1 ,2 ,4 day after enrollment]
the serum level of total bilirubin
- lung function [The outcome will be assessed at the 0, 1 ,2 ,4 day after enrollment]
oxygenation index(PaO2/FiO2),the patients treated with extracorporeal membrane oxygenation will not collect this indicator.
- kidney function(1) [The outcome will be assessed at the 0, 1 ,2 ,4 day after enrollment]
serum level of Creatinine (Cr)
- kidney function(2) [The outcome will be assessed at the 0, 1 ,2 ,4 day after enrollment]
serum level of blood urea nitrogen(BUN)
- kidney function(3) [The outcome will be assessed at the 0, 1 ,2 ,4 day after enrollment]
serum level of Cystatin(Cys)
- inflammatory response(1) [The outcome will be assessed at the 0, 1 ,2 ,4 day after enrollment]
the serum level of interleukin-6(IL-6)
- inflammatory response(2) [The outcome will be assessed at the 0, 1 ,2 ,4 day after enrollment]
the serum level of C-reactive protein(CRP)
- Indicators of infection(1) [The outcome will be assessed at the 0, 1 ,2 ,4 day after enrollment]
the serum level of procalcitonin(PCT)
- Indicators of infection(2) [The outcome will be assessed at the 0, 1 ,2 ,4 day after enrollment]
the level of white blood cell count(WBC)
- The level of lactate [The outcome will be assessed at the 0, 1 ,2 ,4 day after enrollment]
the serum level of lactic acid
- Sequential Organ Failure Assessment (SOFA) score [The outcome will be assessed at the 0, 1 ,2 ,4 day after enrollment]
Organ dysfunction assessed by Sequential Organ Failure Assessment (SOFA) score. SOFA score is based on six different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems. The highest score for each of the six items is 4 points, and the lowest score is 0 points. Finally, the scores of the six items are summed to get the value of the sofa score. The range of the sofa score is 0-24.Higher values represent a worse outcome.
- The cessation of mechanical ventilation(MV) administration [The outcome will be assessed at the 28 day after enrollment]
The duration from the MV administration to the successful cessation in hours( The successful cessation is defined as the termination of MV for more than 48-hours. This outcome measure is intended only for patients receiving MV)
- The cessation of vasoactive drugs administration [The outcome will be assessed at the 28 day after enrollment]
The duration from the vasoactive drugs administration to the successful cessation in hours( The successful cessation is defined as the attainment of a clinician-prescribed mean arterial pressure target for more than 24-hours without the use of vasoactive drugs.This outcome measure is intended only for patients receiving vasoactive drugs)
- The duration of CRRT [The outcome will be assessed at the 28 day after enrollment]
The duration of CRRT therapy in hours( This outcome measure is intended only for patients receiving CRRT)
- ICU length of stay [The outcome will be assessed at the 28 day after enrollment]
ICU length of stay
Other Outcome Measures
- Incidence of adverse events [The outcome will be assessed at the 28 day after enrollment]
A adverse event refers to any adverse medical event that occur after the intervention of trial. The adverse events are not necessarily causally related to the trial treatment.
- Incidence of serious adverse events [The outcome will be assessed at the 28 day after enrollment]
Any adverse medical event occurs at any dose that meets one or more of the following criteria: 1. causes death 2.life-threatening 3. requires hospitalization or hospitalization for an extended period of time 4. causes permanent or significant disability and functional defects 5. causes deformity.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Meets the diagnostic criteria for sepsis-3 developed by the American Society of Critical Care Medicine (SCCM)/European Critical Care Medicine Association (ESICM)
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Age ≥18 years old and age ≤80 years old.
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Procalcitonin ≥2 ng/ml
Exclusion Criteria:
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Age<18 years, or age>80 years.
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Pregnancy or lactating
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A solid-organ or bone marrow transplant patients.
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Patients with myocardial infarction within the past 3 months.
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Advanced pulmonary fibrosis .
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Patients with cardiopulmonary resuscitation before enrollment.
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HIV-positive patients.
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granulocyte-deficient patients.
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blood/lymphatic system tumors are not remission.
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patients with limited care (lack of commitment to full aggressive life support).
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patients with long-term use of immunosuppressive drugs or with immunodeficiency.
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patients with advanced tumors.
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patients combined with non-infectious factors leading to the death(uncontrollable major bleeding, brain hernia, etc.).
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surgically unresolved infection sources(such as some intraperitoneal infection etc.)
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patients allergic to vitamin c.
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patients with G6PD deficiency.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Department of Critical Care Medicine of Dongguan People's Hospital | Dongguan | Guangdong | China | 523059 |
| 2 | Department of Critical Care Medicine of the First People's Hospital of Foshan | Foshan | Guangdong | China | 528000 |
| 3 | Department of Critical Care Medicine of Zhujiang Hospital,Southern Medical University | Guanzhou | Guangdong | China | |
| 4 | Department of Critical Care Medicine of Yunfu People's Hospital | Yunfu | Guangdong | China | 527300 |
| 5 | Department of Critical Care Medicine of Zhongshan People's Hospital | Zhongshan | Guangzhou | China | 528403 |
Sponsors and Collaborators
- Zhujiang Hospital
Investigators
- Principal Investigator: Zhanguo Liu, M.D.PhD, Department of Critical Care Medicine of Zhujiang Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
- Chang P, Liao Y, Guan J, Guo Y, Zhao M, Hu J, Zhou J, Wang H, Cen Z, Tang Y, Liu Z. Combined Treatment With Hydrocortisone, Vitamin C, and Thiamine for Sepsis and Septic Shock: A Randomized Controlled Trial. Chest. 2020 Jul;158(1):174-182. doi: 10.1016/j.chest.2020.02.065. Epub 2020 Mar 31.
- Liu F, Zhu Y, Zhang J, Li Y, Peng Z. Intravenous high-dose vitamin C for the treatment of severe COVID-19: study protocol for a multicentre randomised controlled trial. BMJ Open. 2020 Jul 8;10(7):e039519. doi: 10.1136/bmjopen-2020-039519.
- 2020-KY-069-05