Clinical Efficacy of Megadose Vitamin C in Sepsis
- Registration Number
- NCT05194189
- Lead Sponsor
- Zhujiang Hospital
- 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.
- 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: 234
The number of study center: 4
Study center:
1. Department of Critical Care Medicine of Zhujiang Hospital,Guangzhou, Guangdong, China
2. Department of Critical Care Medicine of The First People's Hospital of Foshan, Foshan, Guangdong, China
3. Department of Critical Care Medicine of Dongguan People's Hospital, Dongguan, Guangdong,China
4. Department of Critical Care Medicine of Yunfu People' s Hospital, Yunfu, Guangdong, China
5. Department of Critical Care Medicine of Zhongshan People's Hospital, Zhongshan, Guangdong, China
Primary endpoint: 28-day all-cause mortality.
Secondary endpoints:
1. The state of liver function: the serum level of transaminase(AST、ALT)、total bilirubin at 96 h after randomization
2. The state of lung function: oxygenation index(PaO2/FiO2) at 96h after randomization
3. The state of kidney function: serum level of Creatinine (Cr)、blood urea nitrogen(BUN)、Cystatin(Cys) at 96 h after randomization
4. The state of inflammatory response: the serum level of interleukin-6(IL-6) and C-reactive protein(CRP) at 96 h after randomization.
5. The state of infection: the serum level of procalcitonin(PCT) and white blood cell （WBC） at 96 h after randomization.
6. The state of circulation system: the serum level of lactate at 96 h after randomization
7. Organ dysfunction assessed by Sequential Organ Failure Assessment (SOFA) score at 96 h after randomization
8. The duration of successful cessation of supportive therapies for organ dysfunction including vasoactive agents, mechanical ventilation.
9. The duration of continuous renal replacement therapy(CRRT)
10. The length of stay in ICU
Safety endpoints：
1. adverse events
2. Serious adverse events
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 234
- 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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo group 5% glucose injection 5% glucose solution 48 ml every 12 h for 4 days or until ICU discharge. Megadose vitamin C group Vitamin C 12 g vitamin C (48 ml) will intravenously injected by a infusion pump every 12 h for 4 days or until ICU discharge
- Primary Outcome Measures
Name Time Method 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
Name Time Method liver function(3) The outcome will be assessed at the 0, 1 ,2 ,4 day after enrollment the serum level of total bilirubin
kidney function(2) The outcome will be assessed at the 0, 1 ,2 ,4 day after enrollment serum level of blood urea nitrogen(BUN)
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)
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)
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)
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 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)
ICU length of stay The outcome will be assessed at the 28 day after enrollment ICU length of stay
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 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)
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(3) The outcome will be assessed at the 0, 1 ,2 ,4 day after enrollment serum level of Cystatin(Cys)
Indicators of infection(1) The outcome will be assessed at the 0, 1 ,2 ,4 day after enrollment the serum level of procalcitonin(PCT)
kidney function(1) The outcome will be assessed at the 0, 1 ,2 ,4 day after enrollment serum level of Creatinine (Cr)
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)
The level of lactate The outcome will be assessed at the 0, 1 ,2 ,4 day after enrollment the serum level of lactic acid
Trial Locations
- Locations (4)
Department of Critical Care Medicine of Zhujiang Hospital,Southern Medical University
🇨🇳Guanzhou, Guangdong, China
Department of Critical Care Medicine of Zhongshan People's Hospital
🇨🇳Zhongshan, Guangzhou, China
Department of Critical Care Medicine of Yunfu People's Hospital
🇨🇳Yunfu, Guangdong, China
Department of Critical Care Medicine of Nanfang Hospital of Southern Medical University
🇨🇳Guanzhou, China