This study investigated whether intravenous vitamin C supplementation could reduce mortality and organ dysfunction in sepsis patients. It was an international randomized controlled triple-blinded trial that assigned 863 adult ICU patients with sepsis to receive either intravenous vitamin C or placebo for 96 hours. The primary outcome of death or persistent organ dysfunction at 28 days occurred in 44.5% of the vitamin C group versus 38.5% of the placebo group, indicating no benefit of vitamin C. Secondary outcomes and safety profiles were also similar between the two groups, suggesting that intravenous vitamin C does not help treat sepsis.

1. PRESENTED BY: Dr.ANITHA.A.V.
MODERATED BY :Dr.BALASUBRAMANYAM

2.  Click to edit Master text styles
 Second level
 Third level
 Fourth level
 Fifth level

5. RESEARCH
QUESTION
• WILL VITAMIN C
SUPPLEMENTATION
REDUCE
MORTALITY AND
ORGAN
DYSFUNCTION IN
PATIENTS WITH
SEPSIS

6. STUDY DESIGN International trial Multi centre
35 adult medical–
surgical ICUs in
Canada, France,
and New Zealand
Randomized
controlled trial
Triple blinded
STUDY
DURATION
November 2018
to July 2021

7. INCLUSION CRITERIA
 >18 years or older with the primary diagnosis of proven or suspected
infection and receiving any dose of vasopressor via continuous infusion,
within 24 hours of admission to the intensive care unit (ICU)
EXCLUSION CRITERIA
1) More than 24 hours of intensive care unit admission
2) Known Glucose-6-phosphate dehydrogenase deficiency
3) Pregnancy;
4) Known allergy to vitamin C
5) Known kidney stones within the past 1 year
6) Receipt of intravenous vitamin C during the current hospitalization
(unless incorporated in parenteral nutrition)
7) Expected death or withdrawal of life-sustaining treatments within 48
hours
8) Previously enrolled in this study
9) Previously enrolled in a trial for which co-enrolment is not allowed (co-
enrolment to be determined case by case)

8. RANDOMIZATION
Patients were randomly assigned to intervention and control group
in 1:1 ratio.
Stratified according to site by means of a centralized Web based
system using permuted blocks of variable, undisclosed size
Patients, clinicians,trial personnel and stasticians for unaware of
trial group assignments.

9. INTERVENTION GROUP
Intravenous vitamin C in a
bolus dose of 50 mg per
kilogram mixed in a 50-ml
solution of either dextrose
5% in water or normal
saline.
Doses were administered
over 30 to 60 minutes
every 6 hours for 96 hours
(i.e., 200 mg per kilogram
per day, with a maximum
of 16 doses)
CONTROL GROUP
Dextrose 5% in water or
normal saline

10. PRIMARY OUTCOME
Composite of death or persistent organ dysfunction (defined as receipt of vasopressors, invasive mechanical ventilation, or new renal-
replacement therapy) on trial day 28
SECONDARY OUTCOMES
Number of days without organ dysfunction in the ICU up to day 28;
Mortality at 28 days and 6 months
Quality of life at 6 months;
Organ failure at days 2, 3, 4, 7, 10, 14, and 28;
Biomarkers of
global tissue dysoxia (lactate),
inflammation (interleukin-1β and tumor necrosis factor α),
endothelial injury (thrombomodulin and angiopoietin-2) at days
3 and 7 days

11.  Quality of life studied by European Quality of Life–5
Dimension 5-Level (EQ-5D-5L) questionnaire
 Organ dysfunction assessed by
SOFA SCORE
APACHE 2 SCORE
 Expected complications of VITAMIN C are monitored
Acute kidney injury
Acute hemolysis
Hypoglycemia

12. Power of study 80%
Estimated mortality in control group 50%
Estimated sample size 400 patients per group
Intention to treat analysis
This trial estimated the risk ratio and 95% confidence
interval for the primary outcome in a generalized linear
mixed model with binomial distribution and a log-link
function, with trial site considered as a random effect.

15.  Baseline characteristics similar in the two groups
 96.7% of the patients received at least 90% of the scheduled doses
of vitamin C or placebo
 ICU median stay 6 days (interquartile range [IQR], 3 to 12) in the
ICU and
 Hospital median stay 16 days (IQR, 8 to 32)
 The use and duration of cointerventions and life-sustaining
therapies during the course of the ICU stay were similar in the two
groups
 The groups had similar urine output and fluid balance during the
first 7 days in the ICU

16. Primary Outcome At day 28
 191 of 429 patients (44.5%) in the vitamin C group had died or
had persistent organ dysfunction, as compared with 167 of
434 patients (38.5%) in the placebo group (risk ratio, 1.21;
95% confidence interval [CI], 1.04 to 1.40; P=0.01)
 In the analysis performed after adjustment for prespecified
baseline characteristics, the risk ratio for the primary
comparison was 1.15 (95% CI, 0.90 to 1.47)

18. SECONDARY OUTCOME
 At 28 days, death had occurred in 152 patients (35.4%) in the vitamin C group
and in 137 patients (31.6%) in the placebo group (risk ratio, 1.17; 95% CI, 0.98 to
1.40).
 The median number of days without organ dysfunction at day 28 was 17 in the
vitamin C group and 19.5 in the placebo group (median difference, −2.43 days;
95% CI, −7.23 to 2.37)
 No differences between groups in
SOFA scores
biomarkers,
6-month survival
health-related quality of life

22. SAFETY OUTCOMES
 No difference in safety outcomes
 One adverse event in vitamin c group ( Anaphysis)
 One patient had severe hypoglycemia group in Vitamin C
group[ that required protocol amendement of glucose
monitoring in many centres]
 No evidence of hemolysis in both groups

25.  In LOVIT trial, the occurrence of death and organ dysfunction
is more in vitamin c group than placebo.
 Biochemical markers has no difference between two groups ,
hence no potential harm is suggested.
 SARS-COV2 Patients with ARDS has beneficial effects in
Vitamin c group found in sub group analysis.
 Results do not support use of Vitamin C in sepsis.

26.  Blinding to limit ascertainment bias,
 A median enrollment time of approximately 12 hours after ICU
admission,
 High protocol adherence
 Assessment of biomarkers
 Assessment of baseline vitamin C levels

27.  Information regarding specific pathogens and the
appropriateness of antimicrobial therapy was not collected.
 Information to ascertain the presence of acute respiratory
distress syndrome at baseline was not collected, so it remains
unclear whether this subgroup had a different response to
vitamin C
 Study done in high income countries, difficult to attribute this
data to middle and low income countries where sepsis case
fatality rate is high.