Hadis Moradbaki, Hanieh Hassani-Pajooh, Mohammad-Amin Valizade-Hasanloei, Shima Hatamkhani, Kiumarth Amini, Maryam Zamanirafe, Maryam Mehrpooya, Abbas Taher
{"title":"一项关于MitoQ治疗感染性休克的双盲、安慰剂对照、随机临床试验:评估其对临床结果和氧化应激生物标志物的影响。","authors":"Hadis Moradbaki, Hanieh Hassani-Pajooh, Mohammad-Amin Valizade-Hasanloei, Shima Hatamkhani, Kiumarth Amini, Maryam Zamanirafe, Maryam Mehrpooya, Abbas Taher","doi":"10.1007/s00210-025-04526-9","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1000,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"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.\",\"authors\":\"Hadis Moradbaki, Hanieh Hassani-Pajooh, Mohammad-Amin Valizade-Hasanloei, Shima Hatamkhani, Kiumarth Amini, Maryam Zamanirafe, Maryam Mehrpooya, Abbas Taher\",\"doi\":\"10.1007/s00210-025-04526-9\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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.</p>\",\"PeriodicalId\":18876,\"journal\":{\"name\":\"Naunyn-Schmiedeberg's archives of pharmacology\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":3.1000,\"publicationDate\":\"2025-08-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Naunyn-Schmiedeberg's archives of pharmacology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s00210-025-04526-9\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Naunyn-Schmiedeberg's archives of pharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00210-025-04526-9","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
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.
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.
期刊介绍:
Naunyn-Schmiedeberg''s Archives of Pharmacology was founded in 1873 by B. Naunyn, O. Schmiedeberg and E. Klebs as Archiv für experimentelle Pathologie und Pharmakologie, is the offical journal of the German Society of Experimental and Clinical Pharmacology and Toxicology (Deutsche Gesellschaft für experimentelle und klinische Pharmakologie und Toxikologie, DGPT) and the Sphingolipid Club. The journal publishes invited reviews, original articles, short communications and meeting reports and appears monthly. Naunyn-Schmiedeberg''s Archives of Pharmacology welcomes manuscripts for consideration of publication that report new and significant information on drug action and toxicity of chemical compounds. Thus, its scope covers all fields of experimental and clinical pharmacology as well as toxicology and includes studies in the fields of neuropharmacology and cardiovascular pharmacology as well as those describing drug actions at the cellular, biochemical and molecular levels. Moreover, submission of clinical trials with healthy volunteers or patients is encouraged. Short communications provide a means for rapid publication of significant findings of current interest that represent a conceptual advance in the field.