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

Sponsor

Universitaire Ziekenhuizen Leuven (Other)

Overall Status

Recruiting

CT.gov ID

NCT04747795

Collaborator

Federaal Kenniscentrum voor Gezondheidszorg, Belgium (Other)

300

Enrollment

Locations

Arms

Anticipated Duration (Months)

37.5

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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?"

Condition or Disease	Intervention/Treatment	Phase
Sepsis Septic Shock Sepsis, Severe	Drug: Vitamin C Drug: Normal saline	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

300 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jun 1, 2021

Anticipated Primary Completion Date :

Oct 5, 2022

Anticipated Study Completion Date :

Jan 1, 2023

Arms and Interventions

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: physiological serum placebo
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

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

Other Names:

physiological serum

placebo

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

Other Names:

Ascorbic Acid

Outcome Measures

Primary Outcome Measures

Sequential Organ Failure Assessment (SOFA) score [5 days]
Average post-baseline patient SOFA score, SOFA score range: 0-24, with 24 being the worst outcome (death)

Secondary Outcome Measures

28-day mortality [28 days]
Maximum SOFA score [5 days]
Maximum SOFA score measured during 5 intervention period. SOFA score ranging from 0 to 24, with 24 begin the worst outcome (death)
Length of hospital stay [3 months]
Total length of hospital stay of the patient (including beyond intervention period)
Length of ICU stay [3 months]
Total length of ICU stay of the patient (including beyond intervention period)
Duration Vasopressors [5 days]
Total duration where vasopression is required (hours)
Dosage Vasopressors [5 days]
Total dosage of Vasopressors required (mcg/kg/min)
need for Renal Replacement Therapy (RRT) [5 days]
was RRT needed
duration of Renal Replacement Therapy (RRT) [5 days]
total duration of RRT (hours)
Ventilator days [3 months]
Total number of days the patient requires ventilator support (including beyond intervention period)
Steroids [5 days]
Total dose of steroids given
Quality of life questionnaire (EQ-5D-5L) [3 months]
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.
Time to return to work [3 months]
Time to return to work of the patient after ED admission (in days)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country
1	GasthuisZusters Antwerpen	Antwerp	Belgium
2	Universitair Ziekenhuis Antwerpen	Antwerp	Belgium
3	Centre Hospitalier Universitaire Saint-Pierre Bruxelles	Brussels	Belgium
4	Universitair Ziekenhuis Brussel	Brussels	Belgium
5	Université Libre de Bruxelles Erasme	Brussels	Belgium
6	Universitaire Ziekenhuizen Leuven	Leuven	Belgium
7	Centre Hospitalier Universitaire de Liège	Liège	Belgium
8	Algemeen Ziekenhuis Turnhout	Turnhout	Belgium