Clinical Efficacy of Megadose Vitamin C in Sepsis

Study Overview
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Brief Summary
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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.

Detailed Description
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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: Department of Critical Care Medicine of Zhujiang Hospital,Guangzhou, Guangdong, China Department of Critical Care Medicine of The First People's Hospital of Foshan, Foshan, Guangdong, China Department of Critical Care Medicine of Dongguan People's Hospital, Dongguan, Guangdong,China Department of Critical Care Medicine of Yunfu People' s Hospital, Yunfu, Guangdong, China Department of Critical Care Medicine of Zhongshan People's Hospital, Zhongshan, Guangdong, China Primary endpoint: 28-day all-cause mortality. Secondary endpoints: The state of liver function: the serum level of transaminase(AST、ALT)、total bilirubin at 96 h after randomization The state of lung function: oxygenation index(PaO2/FiO2) at 96h after randomization The state of kidney function: serum level of Creatinine (Cr)、blood urea nitrogen(BUN)、Cystatin(Cys) at 96 h after randomization The state of inflammatory response: the serum level of interleukin-6(IL-6) and C-reactive protein(CRP) at 96 h after randomization. The state of infection: the serum level of procalcitonin(PCT) and white blood cell （WBC） at 96 h after randomization. The state of circulation system: the serum level of lactate at 96 h after randomization Organ dysfunction assessed by Sequential Organ Failure Assessment (SOFA) score at 96 h after randomization The duration of successful cessation of supportive therapies for organ dysfunction including vasoactive agents, mechanical ventilation. The duration of continuous renal replacement therapy(CRRT) The length of stay in ICU Safety endpoints： adverse events Serious adverse events

Official Title
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Clinical Efficacy of Megadose Vitamin C in Sepsis (CEMVIS): A Multicenter, Randomized, Single-blind, Placebo-controlled Clinical Trial

Conditions
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Sepsis, Septic Shock

Intervention / Treatment
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* Drug: Vitamin C
* Drug: 5% glucose injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Meets the diagnostic criteria for sepsis-3 developed by the American Society of Critical Care Medicine (SCCM)/European Critical Care Medicine Association (ESICM) Age ≥18 years old and age ≤80 years old. Procalcitonin ≥2 ng/ml Exclusion Criteria: Age<18 years, or age>80 years. Pregnancy or lactating A solid-organ or bone marrow transplant patients. Patients with myocardial infarction within the past 3 months. Advanced pulmonary fibrosis . Patients with cardiopulmonary resuscitation before enrollment. HIV-positive patients. granulocyte-deficient patients. blood/lymphatic system tumors are not remission. patients with limited care (lack of commitment to full aggressive life support). patients with long-term use of immunosuppressive drugs or with immunodeficiency. patients with advanced tumors. patients combined with non-infectious factors leading to the death(uncontrollable major bleeding, brain hernia, etc.). surgically unresolved infection sources(such as some intraperitoneal infection etc.) patients allergic to vitamin c. patients with G6PD deficiency.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The participants in treatment group receive intravenous megadose vitamin C. The participants in control group receive 5% glucose injection with same volume.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Megadose vitamin C group<br>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<br>* 12 g vitamin C (48 ml) will be intravenously injected by a infusion pump every 12 h for 4 days or at ICU discharge<br>|
| Placebo Comparator: Placebo group<br>5% glucose solution 48 ml every 12 h for 4 days or until ICU discharge. | Drug: 5% glucose injection<br>* 5% glucose solution 48 ml every 12 h for 4 days or at ICU discharge.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 28-day all-cause mortality | All-cause mortality from the enrollment to the 28th days | The outcome will be assessed at the 28 day after enrollment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| liver function(1) | the serum level of Alanine transaminase(ALT) | The outcome will be assessed at the 0, 1 ,2 ,4 day after enrollment | 
| liver function(2) | the serum level of Aspartate transaminase (AST) | The outcome will be assessed at the 0, 1 ,2 ,4 day after enrollment | 
| liver function(3) | the serum level of total bilirubin | The outcome will be assessed at the 0, 1 ,2 ,4 day after enrollment | 
| lung function | oxygenation index(PaO2/FiO2),the patients treated with extracorporeal membrane oxygenation will not collect this indicator. | The outcome will be assessed at the 0, 1 ,2 ,4 day after enrollment | 
| kidney function(1) | serum level of Creatinine (Cr) | The outcome will be assessed at the 0, 1 ,2 ,4 day after enrollment | 
| kidney function(2) | serum level of blood urea nitrogen(BUN) | The outcome will be assessed at the 0, 1 ,2 ,4 day after enrollment | 
| kidney function(3) | serum level of Cystatin(Cys) | The outcome will be assessed at the 0, 1 ,2 ,4 day after enrollment | 
| inflammatory response(1) | the serum level of interleukin-6(IL-6) | The outcome will be assessed at the 0, 1 ,2 ,4 day after enrollment | 
| inflammatory response(2) | the serum level of C-reactive protein(CRP) | The outcome will be assessed at the 0, 1 ,2 ,4 day after enrollment | 
| Indicators of infection(1) | the serum level of procalcitonin(PCT) | The outcome will be assessed at the 0, 1 ,2 ,4 day after enrollment | 
| Indicators of infection(2) | the level of white blood cell count(WBC) | The outcome will be assessed at the 0, 1 ,2 ,4 day after enrollment | 
| The level of lactate | the serum level of lactic acid | The outcome will be assessed at the 0, 1 ,2 ,4 day after enrollment | 
| Sequential Organ Failure Assessment (SOFA) score | 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 outcome will be assessed at the 0, 1 ,2 ,4 day after enrollment | 
| The cessation of mechanical ventilation(MV) administration | 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 outcome will be assessed at the 28 day after enrollment | 
| The cessation of vasoactive drugs administration | 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 outcome will be assessed at the 28 day after enrollment | 
| The duration of CRRT | The duration of CRRT therapy in hours( This outcome measure is intended only for patients receiving CRRT) | The outcome will be assessed at the 28 day after enrollment | 
| ICU length of stay | ICU length of stay | The outcome will be assessed at the 28 day after enrollment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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megadose vitamin C