A Randomized Trial of Mycobacterium w in Severe Presumed Gram-Negative Sepsis

Abstract

Background: Mycobacterium w (Mw), an immunomodulator, has been shown to resolve early organ failure in severe sepsis.

Research question: Does Mw improve survival in patients with severe presumed gram-negative sepsis?

Study design and methods: This was a randomized, double-blind, placebo-controlled, parallel-group study conducted in ICUs of five tertiary care centers in India. We included consecutive patients (age ≥ 18 years) with presumed gram-negative sepsis in the study within 48 h of the first organ dysfunction. Patients in the treatment arm received 0.3 mL/d of Mw intradermally for 3 consecutive days, whereas the control arm received matching placebo. The primary outcome was 28-day all-cause mortality. The secondary outcomes were ventilator-free days, days receiving vasopressor therapy, ICU and hospital length of stay, nosocomial infection rate, antibiotic use duration, and delta Sequential Organ Failure Assessment (SOFA) score.

Results: We included 202 patients with severe sepsis (101 Mw, 101 placebo). The use of Mw significantly reduced the mortality (9/101 vs 20/101; estimate difference, 0.11 [95% CI, 0.01-0.21]; P = .04). We found no difference in ventilator-free days, days receiving vasopressor drugs, ICU length of stay, and the hospital length of stay. The time to mortality (median, 13 days vs 8.5 days) was significantly longer in the Mw than in the placebo arm. The delta SOFA score, rate of nosocomial infections, and antibiotic use duration were similar in the two arms. We found Mw to reduce significantly the odds (OR, 0.37 [95% CI, 0.15-0.9]) of mortality after adjusting for culture-positive sepsis, baseline SOFA score, age, and sex.

Interpretation: The use of Mw was associated with a significant reduction in mortality in patients with severe presumed gram-negative sepsis. Further studies are required to confirm our findings.

Trial registry: ClinicalTrials.gov; No.: NCT02330432; URL: www.clinicaltrials.gov.

Keywords: Mycobacterium indicus pranii; Mycobacterium w; septic shock; severe sepsis.