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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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| ARM1 | Placebo Comparator |
| |
| Dexmedetomidine | Active Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Dexmedetomidine (DEX) | Drug | 0.5 micrograms per kilogram per hour (0.5 μg/kg/h) |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Heart Rate Variability (HRV) | Heart rate variability will be assessed using continuous electrocardiographic monitoring. The primary HRV parameter analyzed will be the standard deviation of normal-to-normal intervals (SDNN). | From enrollment to the end of treatment at 48 hours |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Sequential Organ Failure Assessment (SOFA) Score | The change in Sequential Organ Failure Assessment (SOFA) score from baseline to 48 hours will be used to evaluate organ dysfunction. | From enrollment to the end of treatment at 48 hours |
| Interleukin-6 (IL-6) level |
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Inclusion Criteria:
Age ≥ 18 year Septic shock defined by Sepsis-3 criteria Enrollment within 24 hours of diagnosis APACHE II score > 10
Exclusion Criteria:
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
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| rongan Liu | Contact | +8615928731511 | 35279240@qq.com |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33865793 | Result | 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. | |
| 33999297 | Result |
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| ID | Term |
|---|---|
| D018805 | Sepsis |
| D012772 | Shock, Septic |
| ID | Term |
|---|---|
| D007239 | Infections |
| D018746 | Systemic Inflammatory Response Syndrome |
| D007249 | Inflammation |
| D010335 | Pathologic Processes |
Not provided
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| ID | Term |
|---|---|
| D020927 | Dexmedetomidine |
| ID | Term |
|---|---|
| D007093 | Imidazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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| Placebo |
| Drug |
0.9% Sodium Chloride Injection |
|
Change in plasma IL-6 levels from baseline to 48 hours |
| From enrollment to the end of treatment at 48 hours |
| ICU length of stay | Duration of ICU stay for each participant | From enrollment to ICU discharge or 90 days, whichever occurs first |
| Duration of Mechanical Ventilation | Total duration of invasive mechanical ventilation during the first 48 hours after enrollment. | From randomization until successful liberation from mechanical ventilation, assessed up to 28 days. |
| Requirement for Renal Replacement Therapy (RRT) | Number of participants requiring renal replacement therapy during the first 48 hours after enrollment. | From randomization to 28 days after randomization. |
| Tumor necrosis factor-α (TNF-α) level | Change in plasma TNF-α levels from baseline to 48 hours | From enrollment to the end of treatment at 48 hours |
| Procalcitonin (PCT) clearance | Percentage change in PCT levels relative to baseline | From enrollment to the end of treatment at 48 hours |
| 28-day all-cause mortality | Proportion of participants who die from any cause within 28 days of enrollment | From enrollment to 28 days |
| 90-day all-cause mortality | Proportion of participants who die from any cause within 90 days of enrollment | From enrollment to 90 days |
| Incidence of new-onset organ dysfunction | Number of participants developing new organ dysfunction during the study period | From enrollment to 90 days or ICU/hospital discharge, whichever occurs first |
| 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. |
| 29290746 | Result | 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. |
| 22477787 | Result | 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. |
| 32844730 | Result | 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. |
| 40019329 | Result | 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 Feb 28. |
| 31112380 | Result | 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. |
| 33729724 | Result | 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. |
| 18698227 | Result | Kurnik D, Friedman EA, Muszkat M, Sofowora GG, Xie HG, Dupont WD, Wood AJ, Stein CM. Genetic variants in the alpha2C-adrenoceptor and G-protein contribute to ethnic differences in cardiovascular stress responses. Pharmacogenet Genomics. 2008 Sep;18(9):743-50. doi: 10.1097/FPC.0b013e3282fee5a1. |
| 30394918 | Result | Morelli A, Sanfilippo F, Arnemann P, Hessler M, Kampmeier TG, D'Egidio A, Orecchioni A, Santonocito C, Frati G, Greco E, Westphal M, Rehberg SW, Ertmer C. The Effect of Propofol and Dexmedetomidine Sedation on Norepinephrine Requirements in Septic Shock Patients: A Crossover Trial. Crit Care Med. 2019 Feb;47(2):e89-e95. doi: 10.1097/CCM.0000000000003520. |
| 31108055 | Result | Dardalas I, Stamoula E, Rigopoulos P, Malliou F, Tsaousi G, Aidoni Z, Grosomanidis V, Milonas A, Papazisis G, Kouvelas D, Pourzitaki C. Dexmedetomidine effects in different experimental sepsis in vivo models. Eur J Pharmacol. 2019 Aug 5;856:172401. doi: 10.1016/j.ejphar.2019.05.030. Epub 2019 May 17. |
| 15187514 | Result | Taniguchi T, Kidani Y, Kanakura H, Takemoto Y, Yamamoto K. Effects of dexmedetomidine on mortality rate and inflammatory responses to endotoxin-induced shock in rats. Crit Care Med. 2004 Jun;32(6):1322-6. doi: 10.1097/01.ccm.0000128579.84228.2a. |
| 23963131 | Result | Geloen A, Chapelier K, Cividjian A, Dantony E, Rabilloud M, May CN, Quintin L. Clonidine and dexmedetomidine increase the pressor response to norepinephrine in experimental sepsis: a pilot study. Crit Care Med. 2013 Dec;41(12):e431-8. doi: 10.1097/CCM.0b013e3182986248. |
| 25457118 | Result | Ostrowski SR, Gaini S, Pedersen C, Johansson PI. Sympathoadrenal activation and endothelial damage in patients with varying degrees of acute infectious disease: an observational study. J Crit Care. 2015 Feb;30(1):90-6. doi: 10.1016/j.jcrc.2014.10.006. Epub 2014 Oct 8. |
| 32520577 | Result | Stolk RF, van der Pasch E, Naumann F, Schouwstra J, Bressers S, van Herwaarden AE, Gerretsen J, Schambergen R, Ruth MM, van der Hoeven JG, van Leeuwen H, Pickkers P, Kox M. Norepinephrine Dysregulates the Immune Response and Compromises Host Defense during Sepsis. Am J Respir Crit Care Med. 2020 Sep 15;202(6):830-842. doi: 10.1164/rccm.202002-0339OC. |
| 28785470 | Result | Chirinos JA, Sweitzer N. Ventricular-Arterial Coupling in Chronic Heart Failure. Card Fail Rev. 2017 Apr;3(1):12-18. doi: 10.15420/cfr.2017:4:2. |
| 32733257 | Result | Carrara M, Herpain A, Baselli G, Ferrario M. Vascular Decoupling in Septic Shock: The Combined Role of Autonomic Nervous System, Arterial Stiffness, and Peripheral Vascular Tone. Front Physiol. 2020 Jul 7;11:594. doi: 10.3389/fphys.2020.00594. eCollection 2020. |
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| 5934857 | Result | Miller G, Chretien L. [Gastric plasmocytoma]. Union Med Can. 1966 Jun;95(6):744-6. No abstract available. French. |
| 32697495 | Result | Deutschman CS, Hellman J, Ferrer Roca R, De Backer D, Coopersmith CM; Research Committee of the Surviving Sepsis Campaign. The Surviving Sepsis Campaign: Basic/Translational Science Research Priorities. Crit Care Med. 2020 Aug;48(8):1217-1232. doi: 10.1097/CCM.0000000000004408. |
| 34605781 | Result | Evans L, Rhodes A, Alhazzani W, Antonelli M, Coopersmith CM, French C, Machado FR, Mcintyre L, Ostermann M, Prescott HC, Schorr C, Simpson S, Wiersinga WJ, Alshamsi F, Angus DC, Arabi Y, Azevedo L, Beale R, Beilman G, Belley-Cote E, Burry L, Cecconi M, Centofanti J, Coz Yataco A, De Waele J, Dellinger RP, Doi K, Du B, Estenssoro E, Ferrer R, Gomersall C, Hodgson C, Hylander Moller M, Iwashyna T, Jacob S, Kleinpell R, Klompas M, Koh Y, Kumar A, Kwizera A, Lobo S, Masur H, McGloughlin S, Mehta S, Mehta Y, Mer M, Nunnally M, Oczkowski S, Osborn T, Papathanassoglou E, Perner A, Puskarich M, Roberts J, Schweickert W, Seckel M, Sevransky J, Sprung CL, Welte T, Zimmerman J, Levy M. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021. Crit Care Med. 2021 Nov 1;49(11):e1063-e1143. doi: 10.1097/CCM.0000000000005337. No abstract available. |
| D013568 |
| Pathological Conditions, Signs and Symptoms |
| D012769 | Shock |