Vitamin A treatment for severe sepsis in humans; a prospective randomized double blind placebo-controlled clinical trial

Abstract

Purpose: To test the benefits of Vitamin A treatment in patients with sepsis on length of time in ICU, days on ventilator, days on intravenous blood pressure support and 28-day mortality. The trial was prospective, randomized and double-blind. As part of a larger sepsis trial, 63 patients with sepsis were randomized to receive either 100,000 IU of Vitamin A intramuscular or placebo over 7-days. Data analysis was by ANOVA with two tailed test and p < 0.05 as significant.

Results: The mean age was 51 ± 2 (mean ± SEM) with 54% female. Groups were well matched with regards to APACHE III score, WBC count, and incidence of bacteremia. In addition, all patients had an ACTH stimulation test using 250 mcg of ACTH IV and serum cortisol was measured at time 0, 30 and 60 min. Baseline cortisol of 24.6 ± 1 mg/dl increased to 41 ± 2 mg/dl at 30 min and 49 ± 2 at 60 min. There was no significant difference between the groups. All cortisol responses were greater than 11.9 mg/dl. Serum Vitamin A level was below normal in 54% of the patients. After randomization, 100,000 IU of Vitamin A daily was given to 32 patients and blinded placebo was given daily to 32 patients for seven days. This was administered as a 1 cc injection of either medication or placebo and was blinded from all but the research pharmacist. The number of days in the ICU was slightly, but not significantly reduced (p = 0.39) by approximately 2 days in the Vitamin A treated patients. The average number of days on blood pressure agents and the day on ventilator were similar. The 28-day mortality rates were similar between the two groups (28 vs 34% placebo vs Vitamin A group). Seven days of high dose intramuscular Vitamin A treatment in patients with sepsis where approximately 50% were vitamin A deficient had no benefit in adults with sepsis.

Trial registration: ClinicalTrials.gov NCT03152474.

Conflict of interest statement

CONFLICT OF INTEREST STATEMENT:

The authors do not have any conflict with manufacture of Aquasol A, the pharmaceutical company that provided the product or any other aspects of this research paper.

Published by Elsevier Ltd.