Moradbaki Hadis, Hassani-Pajooh Hanieh, Valizade-Hasanloei Mohammad-Amin, Hatamkhani Shima, Amini Kiumarth, Zamanirafe Maryam, Mehrpooya Maryam, Taher Abbas
Department of Clinical Pharmacy, School of Pharmacy, Hamadan University of Medical Sciences, Shahid Fahmideh Ave, Hamadan, 6517838678, Iran.
Clinical Research Institute, Imam Khomeini Hospital, Urmia University of Medical Sciences, Urmia, Iran.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Aug 18. doi: 10.1007/s00210-025-04526-9.
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.
这项初步随机临床试验研究了线粒体靶向抗氧化剂甲磺酸盐米托醌（MitoQ）对脓毒性休克患者临床结局和氧化应激生物标志物的影响。42例脓毒性休克患者被随机分为两组，一组接受MitoQ（每日两次，每次20毫克），另一组接受安慰剂，为期5天，同时给予标准治疗。主要终点是序贯器官衰竭评估（SOFA）评分的变化轨迹。次要终点包括氧化应激生物标志物（超氧化物歧化酶[SOD]、过氧化氢酶[CAT]、谷胱甘肽过氧化物酶[GPx]、丙二醛[MDA]）、血管升压药的使用、血管活性药物评分（VIS）、血清乳酸水平、器官支持需求、器官功能恢复情况（第28天SOFA≤2）以及28天死亡率。与安慰剂相比，MitoQ在第5天时显著改善了氧化生物标志物（GPx：+0.14 U/mL，CAT：+15.4 U/mL，SOD：+0.82 U/mL，MDA：-0.86 µmol/L；所有P<0.05）。血清乳酸水平和血管升压药的使用随着显著的治疗×时间交互作用而下降（乳酸：P=0.023；血管升压药：P=0.024），不过在进行多重比较校正后这些差异不再显著。VIS显示出显著的时间变化以及强烈的治疗×时间交互作用（P=0.001），校正后仍具有显著性。血管升压药的使用时长未达到统计学显著性（66.2小时对91.3小时，P=0.087）。在28天死亡率（28.6%对38.1%；P=0.513）、器官功能恢复情况（33.3%对23.8%；P=0.495）或器官支持方面未观察到显著差异。探索性相关性分析表明，SOD和GPx活性的增加与乳酸水平降低有关，而CAT活性的增加与较低的血管升压药剂量相关。MitoQ在脓毒性休克患者中显示出对氧化应激生物标志物的调节作用；然而，其对临床结局的影响仍有待在更大规模、有足够效力的试验中确定。试验注册：该试验于2024年2月29日在伊朗临床试验注册中心（https://irct.behdasht.gov.ir/trial/75681）注册（ID代码：IRCT20120215009014N500）。
