A pilot double-blind, placebo-controlled, randomized clinical trial of MitoQ in the treatment of septic shock: evaluating its effects on clinical outcomes and oxidative stress biomarker.

Abstract

This pilot randomized clinical trial investigated mitoquinone mesylate (MitoQ), a mitochondria-targeted antioxidant, on clinical outcomes and oxidative stress biomarkers in septic shock patients. Forty-two septic shock patients were randomized to receive MitoQ (20 mg twice daily) or placebo for 5 days alongside standard care. The primary endpoint was the trajectory of Sequential Organ Failure Assessment (SOFA) scores. Secondary endpoints included oxidative stress biomarkers (superoxide dismutase [SOD], catalase [CAT], glutathione peroxidase [GPx], malondialdehyde [MDA]), vasopressor use, vasoactive-inotropic scores (VIS), serum lactate, organ support needs, organ failure recovery (SOFA ≤ 2 at day 28), and 28-day mortality. MitoQ significantly improved oxidative biomarkers at day 5 versus placebo (GPx: + 0.14 U/mL, CAT: + 15.4 U/mL, SOD: + 0.82 U/mL, MDA: -0.86 µmol/L; all P < 0.05). Serum lactate and vasopressor use declined with significant Treatment × Time interactions (lactate: P = 0.023; vasopressors: P = 0.024), though these lost significance after multiple comparison correction. VIS showed significant temporal changes and a robust Treatment × Time interaction (P = 0.001), remaining significant after correction. Vasopressor duration did not reach statistical significance (66.2 vs. 91.3 h, P = 0.087). No significant differences were observed in 28-day mortality (28.6% vs. 38.1%; P = 0.513), organ recovery (33.3% vs. 23.8%; P = 0.495), or organ support. Exploratory correlations showed that increases in SOD and GPx activity were linked to lactate reduction, and increased CAT activity was associated with lower vasopressor dose. MitoQ demonstrated modulation of oxidative stress biomarkers in patients with septic shock; however, its impact on clinical outcomes remains to be established in larger, adequately powered trials.Trial registration: The trial was registered at Iranian Registry of Clinical Trials ( https://irct.behdasht.gov.ir/trial/75681 ) (ID code: IRCT20120215009014N500) on February 29, 2024.