Clinical Efficacy of Megadose Vitamin C in Sepsis (CEMVIS)

Zhujiang Hospital

Status and phase: Enrolling; Phase 2

Conditions: Septic Shock; Sepsis

Treatments: Drug: Vitamin C; Drug: 5% glucose injection

Study type: Interventional

Funder types: Other

Identifiers

NCT05194189

2020-KY-069-05

Details and patient eligibility

About

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.

Full 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

Enrollment: 234 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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234 participants in 2 patient groups, including a placebo group

Megadose vitamin C group

Experimental group

Description:

12 g vitamin C (48 ml) will intravenously injected by a infusion pump every 12 h for 4 days or until ICU discharge

Treatment:

Drug: Vitamin C

Placebo group

Placebo Comparator group

Description:

5% glucose solution 48 ml every 12 h for 4 days or until ICU discharge.

Treatment:

Drug: 5% glucose injection