Early Administration of Vitamin C in Patients With Sepsis or Septic Shock in Emergency Departments

NCT04747795 | Completed Phase 3 DMC

• 3 other identifiers: S632132020-001862-12KCE 19-1237
• Study Type: interventional
• Target: 301
• Locations: 1 country
• Sites: 8

Brief Summary

In this clinical trial the effect of early administration of Vitamin C is investigated in patients admitted at the emergency department with sepsis or septic shock. When a patient has sepsis, his/her body is causing damage to its own tissues and organs as result of an infection. This can lead to septic shock. The patient has a low blood pressure, his/her organs stop working and the patient may even die. The aim of this trial is to investigate the efficiency of Vitamin C in sepsis and septic shock. Vitamin C is a vitamin present in various foods and has been approved as dietary supplement by the Belgian authorities. Over the years it has been proven that Vitamin C is very safe. In addition, several studies have shown that Vitamin C can also have a protective effect. It can reduce organ damage and increase survival rates. Although several studies suggest that Vitamin C can help fight sepsis, it is not yet used in practice. This Belgian trial, in which several hospitals participate, hopes to provide a clear answer to the question: "Should Vitamin C be administered to patients admitted in an emergency department with sepsis or septic shock?"

Conditions

Sepsis; Septic Shock; Sepsis, Severe

Keywords

Vitamin C; ascorbic acid; sepsis; septic shock; RCT

Outcome Measures

Primary Outcomes (1)

• Sequential Organ Failure Assessment (SOFA) score

  Average post-baseline patient SOFA score, SOFA score range: 0-24, with 24 being the worst outcome (death)

  5 days

Secondary Outcomes (12)

• 28-day mortality

  28 days

• Maximum SOFA score

  5 days

• Length of hospital stay

  3 months

• Length of ICU stay

  3 months

• Duration Vasopressors

  5 days

Study Arms (2)

standard care + placebo

PLACEBO COMPARATOR

The 'standard care' group will receive intermittent infusion of normal saline (3 ampoules of 5 ml 9mg/ml normal saline diluted in 50 ml of normal saline, every 6 hours) during 4 days or until hospital discharge and is started within 6 hours after presentation (time of triage) in the ED.

Drug: Normal saline

standard care + Vitamin C

ACTIVE COMPARATOR

The 'standard care + Vitamin C' group will receive intermittent infusion of Vitamin C (3 ampoules of 500 mg/5ml Vitamin C diluted in 50 ml of normal saline, every 6 hours) during 4 days or until hospital discharge and is started within 6 hours after presentation (time of triage) in the ED.

Drug: Vitamin C

Interventions

Vitamin C DRUG

IV

Also known as: Ascorbic Acid

standard care + Vitamin C

Normal saline DRUG

IV

Also known as: physiological serum, placebo

standard care + placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient has a 'suspected infection': this requires the combination of antibiotic administration and body fluid cultures within the first 6 hours after Emergency Department presentation.
• Patient has a NEWS score ≥ 5.

You may not qualify if:

• Patient (≥18 years old) or legally authorized representative didn't provide informed consent. Delayed informed consent can be applied in cases where the patient is critically ill and no LAR is available.
• antibiotic administration as a single dose or as a prophylactic treatment.
• antibiotics administered without an accompanying body fluid culture according to the timeframe (within 6 hours after emergency department presentation).
• 'Do no intubate' or 'comfort measures only' status.
• Failure to randomize within 6 hours after Emergency Department presentation.
• Weight \< 45 kg.
• Pregnant or breastfeeding.
• Known allergy for Vitamin C.
• Known history of oxalate nephropathy or hyperoxaluria.
• Known history of glucose-6-phosphate dehydrogenase deficiency.
• Known history of chronic iron overload due to iron storage and other diseases.
• The patient is already on IV steroids for a reason other than septic shock.
• Proven active COVID-19 infection (positive swab and/or CT scan positive for COVID-19 within 14 days prior to or at ED presentation).
• Participation in an interventional trial with an investigational medicinal product (IMP) or device

Sponsors & Collaborators

• Universitaire Ziekenhuizen KU Leuven: lead
• Federaal Kenniscentrum voor Gezondheidszorg, Belgium: collaborator

Study Sites (8)

GasthuisZusters Antwerpen

Antwerp, Belgium

Location

Universitair Ziekenhuis Antwerpen

Antwerp, Belgium

Location

Centre Hospitalier Universitaire Saint-Pierre Bruxelles

Brussels, Belgium

Location

Universitair Ziekenhuis Brussel

Brussels, Belgium

Location

Université Libre de Bruxelles Erasme

Brussels, Belgium

Location

Universitaire Ziekenhuizen Leuven

Leuven, Belgium

Location

Centre Hospitalier Universitaire de Liège

Liège, Belgium

Location

Algemeen Ziekenhuis Turnhout

Turnhout, Belgium

Location

Related Publications (2)

• Vandervelden S, Cortens B, Fieuws S, Eegdeman W, Malinverni S, Vanhove P, Monsieurs K, Breuls J, Hubloue I, Stifkens F, Creteur J, Wauters L, Desruelles D; C-EASIE investigators. Early administration of vitamin C in patients with sepsis or septic shock in emergency departments: a multicenter, double-blind, randomized controlled trial: the C-EASIE trial. Crit Care. 2025 Apr 23;29(1):160. doi: 10.1186/s13054-025-05383-x.

  PMID: 40269974 DERIVED

• Vandervelden S, Wauters L, Breuls J, Fieuws S, Vanhove P, Hubloue I, Bartiaux M, Creteur J, Stifkens F, Monsieurs K, Desruelles D. Early administration of Vitamin C in patients with sepsis or septic shock in emergency departments: A multicenter, double blinded, randomized controlled trial: The C-EASIE trial protocol. PLoS One. 2021 Nov 5;16(11):e0259699. doi: 10.1371/journal.pone.0259699. eCollection 2021.

  PMID: 34739527 DERIVED

MeSH Terms

Conditions

Sepsis; Shock, Septic

Interventions

Ascorbic Acid; Saline Solution

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Intervention Hierarchy (Ancestors)

Sugar Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Hydroxy Acids; Carbohydrates; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Didier Desruelles, MD

  Universitaire Ziekenhuizen KU Leuven

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 4, 2021
• First Posted: February 10, 2021
• Study Start: June 1, 2021
• Primary Completion: August 31, 2023
• Study Completion: November 15, 2023
• Last Updated: January 25, 2024

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

BE (8)