Early Administration of Vitamin C in Patients With Sepsis or Septic Shock in Emergency Departments (c-easie)

Early Administration of Vitamin C in Patients With Sepsis or Septic Shock in Emergency Departments: a Multicentre, Double Blinded, Randomized Controlled Trial: the C-EASIE Trial

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?"

Study Overview

• Status: Completed
• Conditions: Sepsis; Septic Shock; Sepsis, Severe
• Intervention / Treatment: Drug: Normal saline; Drug: Vitamin C

• Study Type: Interventional
• Enrollment (Actual): 301
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Lina Wauters, PhD; Phone Number: +3216345820; Email: lina.wauters@uzleuven.be
• Study Contact Backup: Name: Stefanie Vandervelden, MD; Phone Number: +3216 345405; Email: stefanie.vandervelden@uzleuven.be

Study Locations

• Belgium
  • Antwerp, Belgium
    • Universitair Ziekenhuis Antwerpen
  • Antwerp, Belgium
    • GasthuisZusters Antwerpen
  • Brussels, Belgium
    • Universitair Ziekenhuis Brussel
  • Brussels, Belgium
    • Centre Hospitalier Universitaire Saint-Pierre Bruxelles
  • Brussels, Belgium
    • Université Libre de Bruxelles Erasme
  • Leuven, Belgium
    • Universitaire Ziekenhuizen Leuven
  • Liège, Belgium
    • Centre Hospitalier Universitaire de Liège
  • Turnhout, Belgium
    • Algemeen Ziekenhuis Turnhout

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: standard care + placebo; 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; IV; Other Names: placebo; physiological serum
Active Comparator: standard care + Vitamin C; 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; IV; Other Names: Ascorbic Acid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
28-day mortality		28 days
Maximum SOFA score	Maximum SOFA score measured during 5 intervention period. SOFA score ranging from 0 to 24, with 24 begin the worst outcome (death)	5 days
Length of hospital stay	Total length of hospital stay of the patient (including beyond intervention period)	3 months
Length of ICU stay	Total length of ICU stay of the patient (including beyond intervention period)	3 months
Duration Vasopressors	Total duration where vasopression is required (hours)	5 days
Dosage Vasopressors	Total dosage of Vasopressors required (mcg/kg/min)	5 days
need for Renal Replacement Therapy (RRT)	was RRT needed	5 days
duration of Renal Replacement Therapy (RRT)	total duration of RRT (hours)	5 days
Ventilator days	Total number of days the patient requires ventilator support (including beyond intervention period)	3 months
Steroids	Total dose of steroids given	5 days
Quality of life questionnaire (EQ-5D-5L)	The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. This decision results in a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state. The EQ VAS records the patient's self-rated health on a vertical visual analogue scale, where the endpoints are labelled 'The best health you can imagine' and 'The worst health you can imagine'. The VAS can be used as a quantitative measure of health outcome that reflect the patient's own judgement.	3 months
Time to return to work	Time to return to work of the patient after ED admission (in days)	3 months

Collaborators and Investigators

• Sponsor: Universitaire Ziekenhuizen KU Leuven
• Collaborators: Federaal Kenniscentrum voor Gezondheidszorg, Belgium
• Investigators: Principal Investigator: Didier Desruelles, MD, Universitaire Ziekenhuizen KU Leuven

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2021
• Primary Completion (Actual): August 31, 2023
• Study Completion (Actual): November 15, 2023

Study Registration Dates

• First Submitted: February 4, 2021
• First Submitted That Met QC Criteria: February 9, 2021
• First Posted (Actual): February 10, 2021

Study Record Updates

• Last Update Posted (Estimated): January 25, 2024
• Last Update Submitted That Met QC Criteria: January 23, 2024
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: septic shock; RCT; sepsis; Vitamin C; ascorbic acid
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Disease Attributes; Sepsis; Toxemia; Emergencies; Shock, Septic; Shock; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Protective Agents; Micronutrients; Vitamins; Antioxidants; Ascorbic Acid
• Other Study ID Numbers: S63213; 2020-001862-12 (EudraCT Number); KCE 19-1237 (Other Grant/Funding Number: Federaal kenniscentrum voor de gezondheidszorg (KCE))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No