Early Dexmedetomidine and Sympathetic Regulation in Sepsis

Официальное название

A Prospective Study on the Effects of Early Dexmedetomidine Administration on Sympathetic Nervous System Activity, Pathophysiological Mechanisms, and Clinical Outcomes in Sepsis

Обзор

The goal of this clinical trial is to learn whether early administration of dexmedetomidine can improve autonomic nervous system regulation and clinical outcomes in adult patients with septic shock. It will also evaluate the safety of dexmedetomidine in this population. The main questions it aims to answer are: Does early dexmedetomidine improve sympathetic nervous system activity, as measured by heart rate variability (HRV) and blood pressure variability (BPV)? Does dexmedetomidine reduce endogenous catecholamine levels and vasopressor requirements? Does early autonomic modulation improve organ function and survival outcomes in septic shock? Researchers will compare dexmedetomidine to a placebo (normal saline) to determine whether dexmedetomidine improves hemodynamic stability and prognosis in patients with septic shock. Participants will: Be randomly assigned to receive dexmedetomidine (0.5 μg/kg/h) or placebo by continuous intravenous infusion for 48 hours Undergo continuous ECG and invasive blood pressure monitoring Have blood samples collected at predefined time points to measure inflammatory markers and endogenous catecholamine levels Be assessed for organ function, vasopressor use, and perfusion parameters during the first 48 hours Be followed up for 28-day and 90-day survival outcomes

Вмешательства

• Препарат Dexmedetomidine (DEX)
  0.5 micrograms per kilogram per hour (0.5 μg/kg/h)
• Препарат Placebo
  0.9% Sodium Chloride Injection

Первичные конечные точки

• Heart Rate Variability (HRV) [Срок оценки: From enrollment to the end of treatment at 48 hours]

Вторичные конечные точки (10)

• Change in Sequential Organ Failure Assessment (SOFA) Score [Срок оценки: From enrollment to the end of treatment at 48 hours]
• Interleukin-6 (IL-6) level [Срок оценки: From enrollment to the end of treatment at 48 hours]
• ICU length of stay [Срок оценки: From enrollment to ICU discharge or 90 days, whichever occurs first]
• Duration of Mechanical Ventilation [Срок оценки: From randomization until successful liberation from mechanical ventilation, assessed up to 28 days.]
• Requirement for Renal Replacement Therapy (RRT) [Срок оценки: From randomization to 28 days after randomization.]
• Tumor necrosis factor-α (TNF-α) level [Срок оценки: From enrollment to the end of treatment at 48 hours]
• Procalcitonin (PCT) clearance [Срок оценки: From enrollment to the end of treatment at 48 hours]
• 28-day all-cause mortality [Срок оценки: From enrollment to 28 days]
• 90-day all-cause mortality [Срок оценки: From enrollment to 90 days]
• Incidence of new-onset organ dysfunction [Срок оценки: From enrollment to 90 days or ICU/hospital discharge, whichever occurs first]

Критерии участия

Критерии включения

Age ≥ 18 year Septic shock defined by Sepsis-3 criteria Enrollment within 24 hours of diagnosis APACHE II score > 10

Критерии исключения

Pregnancy or lactation Second- or third-degree atrioventricular block Persistent bradycardia (HR <50 bpm) requiring intervention Hypersensitivity to dexmedetomidine Norepinephrine dose >0.5 μg/kg/min End-stage disease or life expectancy <72 hours Any condition deemed unsuitable by the investigator

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Тройное слепое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Публикации

• Kim D, Park Y, Choi KH, Park TK, Lee JM, Cho YH, Choi JO, Jeon ES, Yang JH. Prognostic Implication of RV Coupling to Pulmonary Circulation for Successful Weaning From Extracorporeal Membrane Oxygenation. JACC Cardiovasc Imaging. 2021 Aug;14(8):1523-1531. doi: 10.1016/j.jcmg.2021.02.018. Epub 2021 Apr 14. PMID 33865793
• Carrara M, Ferrario M, Bollen Pinto B, Herpain A. The autonomic nervous system in septic shock and its role as a future therapeutic target: a narrative review. Ann Intensive Care. 2021 May 17;11(1):80. doi: 10.1186/s13613-021-00869-7. PMID 33999297
• Haenecour AS, Seto W, Urbain CM, Stephens D, Laussen PC, Balit CR. Prolonged Dexmedetomidine Infusion and Drug Withdrawal In Critically Ill Children. J Pediatr Pharmacol Ther. 2017 Nov-Dec;22(6):453-460. doi: 10.5863/1551-6776-22.6.453. PMID 29290746
• Tobias JD. Dexmedetomidine: Are There Going to be Issues with Prolonged Administration? J Pediatr Pharmacol Ther. 2010 Jan;15(1):4-9. No abstract available. PMID 22477787
• Ammar MA, Sacha GL, Welch SC, Bass SN, Kane-Gill SL, Duggal A, Ammar AA. Sedation, Analgesia, and Paralysis in COVID-19 Patients in the Setting of Drug Shortages. J Intensive Care Med. 2021 Feb;36(2):157-174. doi: 10.1177/0885066620951426. Epub 2020 Aug 26. PMID 32844730
• Dargent A, Bourredjem A, Jacquier M, Bohe J, Argaud L, Levy B, Fournel I, Cransac A, Badie J, Quintin L, Quenot JP. Dexmedetomidine to Reduce Vasopressor Resistance in Refractory Septic Shock: alpha2 Agonist Dexmedetomidine for REfractory Septic Shock (ADRESS): A Double-Blind Randomized Controlled Pilot Trial. Crit Care Med. 2025 Apr 1;53(4):e884-e896. doi: 10.1097/CCM.0000000000006608. Epub 2025 PMID 40019329
• Shehabi Y, Howe BD, Bellomo R, Arabi YM, Bailey M, Bass FE, Bin Kadiman S, McArthur CJ, Murray L, Reade MC, Seppelt IM, Takala J, Wise MP, Webb SA; ANZICS Clinical Trials Group and the SPICE III Investigators. Early Sedation with Dexmedetomidine in Critically Ill Patients. N Engl J Med. 2019 Jun 27;380(26):2506-2517. doi: 10.1056/NEJMoa1904710. Epub 2019 May 19. PMID 31112380
• Grayson KE, Bailey M, Balachandran M, Banneheke PP, Belletti A, Bellomo R, Naorungroj T, Serpa-Neto A, Wright JD, Yanase F, Young PJ, Shehabi Y. The Effect of Early Sedation With Dexmedetomidine on Body Temperature in Critically Ill Patients. Crit Care Med. 2021 Jul 1;49(7):1118-1128. doi: 10.1097/CCM.0000000000004935. PMID 33729724

Идентификаторы

NCT: NCT07470775 · IRB No. 927-1 (2025)

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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