Clinical trial NCT05194189: Clinical Efficacy of Megadose Vitamin C in Sepsis
Official title: Clinical Efficacy of Megadose Vitamin C in Sepsis (CEMVIS): A Multicenter, Randomized, Single-blind, Placebo-controlled Clinical Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Sepsis
Septic Shock
Keywords: megadose vitamin C
Lead sponsor: Zhujiang Hospital
Sponsor class: OTHER
First posted: 2022-01-18
Enrollment: 234
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The participants in treatment group receive intravenous megadose vitamin C. The participants in control group receive 5% glucose injection with same volume.
Primary purpose: TREATMENT

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

Eligibility criteria: 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.

Primary outcomes:
measure: 28-day all-cause mortality
timeFrame: The outcome will be assessed at the 28 day after enrollment
Secondary outcomes:
measure: liver function(1)
timeFrame: The outcome will be assessed at the 0, 1 ,2 ,4 day after enrollment
measure: liver function(2)
timeFrame: The outcome will be assessed at the 0, 1 ,2 ,4 day after enrollment
measure: liver function(3)
timeFrame: The outcome will be assessed at the 0, 1 ,2 ,4 day after enrollment
measure: lung function
timeFrame: The outcome will be assessed at the 0, 1 ,2 ,4 day after enrollment
measure: kidney function(1)
timeFrame: The outcome will be assessed at the 0, 1 ,2 ,4 day after enrollment
measure: kidney function(2)
timeFrame: The outcome will be assessed at the 0, 1 ,2 ,4 day after enrollment
measure: kidney function(3)
timeFrame: The outcome will be assessed at the 0, 1 ,2 ,4 day after enrollment
measure: inflammatory response(1)
timeFrame: The outcome will be assessed at the 0, 1 ,2 ,4 day after enrollment
measure: inflammatory response(2)
timeFrame: The outcome will be assessed at the 0, 1 ,2 ,4 day after enrollment
measure: Indicators of infection(1)
timeFrame: The outcome will be assessed at the 0, 1 ,2 ,4 day after enrollment
measure: Indicators of infection(2)
timeFrame: The outcome will be assessed at the 0, 1 ,2 ,4 day after enrollment
measure: The level of lactate
timeFrame: The outcome will be assessed at the 0, 1 ,2 ,4 day after enrollment
measure: Sequential Organ Failure Assessment (SOFA) score
timeFrame: The outcome will be assessed at the 0, 1 ,2 ,4 day after enrollment
measure: The cessation of mechanical ventilation(MV) administration
timeFrame: The outcome will be assessed at the 28 day after enrollment
measure: The cessation of vasoactive drugs administration
timeFrame: The outcome will be assessed at the 28 day after enrollment
measure: The duration of CRRT
timeFrame: The outcome will be assessed at the 28 day after enrollment
measure: ICU length of stay
timeFrame: The outcome will be assessed at the 28 day after enrollment
Other outcomes:
measure: Incidence of adverse events
timeFrame: The outcome will be assessed at the 28 day after enrollment
measure: Incidence of serious adverse events
timeFrame: The outcome will be assessed at the 28 day after enrollment
Locations:
city: Guanzhou
country: China
facility: Department of Critical Care Medicine of Zhujiang Hospital,Southern Medical University
state: Guangdong
city: Yunfu
country: China
facility: Department of Critical Care Medicine of Yunfu People's Hospital
state: Guangdong
city: Zhongshan
country: China
facility: Department of Critical Care Medicine of Zhongshan People's Hospital
state: Guangzhou
city: Guanzhou
country: China
facility: Department of Critical Care Medicine of Nanfang Hospital of Southern Medical University
Study officials:
affiliation: Department of Critical Care Medicine of Zhujiang Hospital
name: Zhanguo Liu, M.D.PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.