Low-Dose Dexmedetomidine for Delirium Prevention in Mechanically Ventilated Septic Patients

NCT04876937 | Terminated DMC

• 1 other identifier: 2020-241
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

Delirium is common in septic patients, especially those receiving mechanical ventilation in the intensive care unit (ICU). Dexmedetomidine is a highly selective α2 adrenoreceptor agonist with anxiolytic, sedative, analgesic, and anti-inflammatory effects. Use of dexmedetomidine in mechanically ventilated ICU patients is associated with less delirium and improved outcomes. However, dexmedetomidine infusion produces dose-dependent bradycardia and hypotension; these limited the use of dexmedetomidine in ICU patients. This study is designed to test the hypothesis that low-dose dexmedetomidine infusion can also reduce delirium in mechanically ventilated ICU patients with sepsis.

Conditions

Adult; Intensive Care Unit; Sepsis; Mechanical Ventilation; Delirium; Dexmedetomidine

Keywords

Adult; Intensive care unit; Sepsis; Mechanical ventilation; Delirium; Dexmedetomidine

Outcome Measures

Primary Outcomes (1)

• Incidence of delirium within the first 7 days after enrollment

  Delirium is assessed twice daily (from 06:00 to 10:00 and from 18:00 to 20:00) with the Confusion Assessment Method for the intensive care unit (CAM-ICU).

  Up to 7 days after enrollment

Secondary Outcomes (7)

• Duration of mechanical ventilation.

  Up to 30 days after enrollment

• Length of stay in the ICU.

  Up to 30 days after enrollment

• Length of stay in the hospital.

  Up to 30 days after enrollment

• Incidence of non-delirium complications.

  Up to 30 days after enrollment

• All-cause 30-day mortality

  Up to 30 days after enrollment

Other Outcomes (8)

• Pain intensity.

  Up to 7 days after enrollment.

• Subjective sleep quality.

  Up to 7 days after enrollment.

• Score of Acute Physiology and Chronic Health Evaluation II (APACHE II).

  Within 24 hours after enrollment.

Study Arms (2)

Dexmedetomidine group

EXPERIMENTAL

Dexmedetomidine is infused at a rate of 0.1-0.2 ug/kg/h during mechanical ventilation, for a maximum of 7 days.

Drug: Dexmedetomidine

Placebo group

PLACEBO COMPARATOR

Placebo (normal saline) is infused at a same rate as in the dexmedetomidine group during mechanical ventilation, for a maximum of 7 days.

Drug: Placebo (normal saline)

Interventions

Dexmedetomidine DRUG

Dexmedetomidine is infused at a rate of 0.1-0.2 μg/kg/h (0.025-0.05 ml/kg/h) from study recruitment in the ICU during mechanical ventilation, for no more than 7 days.

Also known as: Dexmedetomidine hydrochloride

Dexmedetomidine group

Placebo (normal saline) DRUG

Placebo (normal saline) is infused at a rate of 0.025-0.05 ml/kg/h from study recruitment in the ICU during mechanical ventilation, for no more than 7 days.

Also known as: Normal saline

Placebo group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 18 years or older;
• Admitted to the ICU;
• With expected mechanical ventilation duration ≥12 hours;
• Meet the diagnostic criteria of sepsis (sepsis 3.0; patient with infection and a sequential organ failure assessment score ≥2).

You may not qualify if:

• Refuse to participate in;
• Pregnancy;
• History of schizophrenia, epilepsy, parkinsonism, or myasthenia gravis;
• Inability to communicate (coma, profound dementia, or language barrier);
• Brain injury or neurosurgery;
• Left ventricular ejection fraction (LVEF) less than 30%, sick sinus syndrome, severe sinus bradycardia (\<50 beats per min \[bpm\]), or second degree or greater atrioventricular block without pacemaker;
• Serious hepatic dysfunction (Child-Pugh class C);
• Serious renal dysfunction (undergoing dialysis);
• With expected survival for no more than 24 hours;
• Allergic to dexmedetomidine;
• Other conditions that were considered unsuitable for study participation.

Sponsors & Collaborators

• Peking University First Hospital: lead
• China-Japan Friendship Hospital: collaborator
• Beijing Hospital: collaborator
• Beijing Friendship Hospital: collaborator
• Beijing Shijitan Hospital, Capital Medical University: collaborator
• Beijing Tongren Hospital: collaborator

Study Sites (1)

Peking University First Hospital

Beijing, Beijing Municipality, 100034, China

Location

Related Publications (20)

• Guenther U, Radtke FM. Delirium in the postanaesthesia period. Curr Opin Anaesthesiol. 2011 Dec;24(6):670-5. doi: 10.1097/ACO.0b013e32834c7b44.

  PMID: 21971396 BACKGROUND

• Roberts B, Rickard CM, Rajbhandari D, Turner G, Clarke J, Hill D, Tauschke C, Chaboyer W, Parsons R. Multicentre study of delirium in ICU patients using a simple screening tool. Aust Crit Care. 2005 Feb;18(1):6, 8-9, 11-4 passim. doi: 10.1016/s1036-7314(05)80019-0.

  PMID: 18038529 BACKGROUND

• Ely EW, Gautam S, Margolin R, Francis J, May L, Speroff T, Truman B, Dittus R, Bernard R, Inouye SK. The impact of delirium in the intensive care unit on hospital length of stay. Intensive Care Med. 2001 Dec;27(12):1892-900. doi: 10.1007/s00134-001-1132-2. Epub 2001 Nov 8.

  PMID: 11797025 BACKGROUND

• Balas MC, Happ MB, Yang W, Chelluri L, Richmond T. Outcomes Associated With Delirium in Older Patients in Surgical ICUs. Chest. 2009 Jan;135(1):18-25. doi: 10.1378/chest.08-1456. Epub 2008 Nov 18.

  PMID: 19017895 BACKGROUND

• Ansaloni L, Catena F, Chattat R, Fortuna D, Franceschi C, Mascitti P, Melotti RM. Risk factors and incidence of postoperative delirium in elderly patients after elective and emergency surgery. Br J Surg. 2010 Feb;97(2):273-80. doi: 10.1002/bjs.6843.

  PMID: 20069607 BACKGROUND

• Ely EW, Shintani A, Truman B, Speroff T, Gordon SM, Harrell FE Jr, Inouye SK, Bernard GR, Dittus RS. Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit. JAMA. 2004 Apr 14;291(14):1753-62. doi: 10.1001/jama.291.14.1753.

  PMID: 15082703 BACKGROUND

• Franco K, Litaker D, Locala J, Bronson D. The cost of delirium in the surgical patient. Psychosomatics. 2001 Jan-Feb;42(1):68-73. doi: 10.1176/appi.psy.42.1.68.

  PMID: 11161124 BACKGROUND

• Abelha FJ, Luis C, Veiga D, Parente D, Fernandes V, Santos P, Botelho M, Santos A, Santos C. Outcome and quality of life in patients with postoperative delirium during an ICU stay following major surgery. Crit Care. 2013 Oct 29;17(5):R257. doi: 10.1186/cc13084.

  PMID: 24168808 BACKGROUND

• Van Rompaey B, Schuurmans MJ, Shortridge-Baggett LM, Truijen S, Elseviers M, Bossaert L. Long term outcome after delirium in the intensive care unit. J Clin Nurs. 2009 Dec;18(23):3349-57. doi: 10.1111/j.1365-2702.2009.02933.x. Epub 2009 Sep 4.

  PMID: 19735334 BACKGROUND

• Bickel H, Gradinger R, Kochs E, Forstl H. High risk of cognitive and functional decline after postoperative delirium. A three-year prospective study. Dement Geriatr Cogn Disord. 2008;26(1):26-31. doi: 10.1159/000140804. Epub 2008 Jun 24.

  PMID: 18577850 BACKGROUND

• Pisani MA, Kong SY, Kasl SV, Murphy TE, Araujo KL, Van Ness PH. Days of delirium are associated with 1-year mortality in an older intensive care unit population. Am J Respir Crit Care Med. 2009 Dec 1;180(11):1092-7. doi: 10.1164/rccm.200904-0537OC. Epub 2009 Sep 10.

  PMID: 19745202 BACKGROUND

• Kawazoe Y, Miyamoto K, Morimoto T, Yamamoto T, Fuke A, Hashimoto A, Koami H, Beppu S, Katayama Y, Itoh M, Ohta Y, Yamamura H; Dexmedetomidine for Sepsis in Intensive Care Unit Randomized Evaluation (DESIRE) Trial Investigators. Effect of Dexmedetomidine on Mortality and Ventilator-Free Days in Patients Requiring Mechanical Ventilation With Sepsis: A Randomized Clinical Trial. JAMA. 2017 Apr 4;317(13):1321-1328. doi: 10.1001/jama.2017.2088.

  PMID: 28322414 BACKGROUND

• Wunsch H, Kahn JM, Kramer AA, Wagener G, Li G, Sladen RN, Rubenfeld GD. Dexmedetomidine in the care of critically ill patients from 2001 to 2007: an observational cohort study. Anesthesiology. 2010 Aug;113(2):386-94. doi: 10.1097/ALN.0b013e3181e74116.

  PMID: 20613466 BACKGROUND

• van Vught LA, Klein Klouwenberg PM, Spitoni C, Scicluna BP, Wiewel MA, Horn J, Schultz MJ, Nurnberg P, Bonten MJ, Cremer OL, van der Poll T; MARS Consortium. Incidence, Risk Factors, and Attributable Mortality of Secondary Infections in the Intensive Care Unit After Admission for Sepsis. JAMA. 2016 Apr 12;315(14):1469-79. doi: 10.1001/jama.2016.2691.

  PMID: 26975785 BACKGROUND

• Nelson LE, Lu J, Guo T, Saper CB, Franks NP, Maze M. The alpha2-adrenoceptor agonist dexmedetomidine converges on an endogenous sleep-promoting pathway to exert its sedative effects. Anesthesiology. 2003 Feb;98(2):428-36. doi: 10.1097/00000542-200302000-00024.

  PMID: 12552203 BACKGROUND

• Djaiani G, Silverton N, Fedorko L, Carroll J, Styra R, Rao V, Katznelson R. Dexmedetomidine versus Propofol Sedation Reduces Delirium after Cardiac Surgery: A Randomized Controlled Trial. Anesthesiology. 2016 Feb;124(2):362-8. doi: 10.1097/ALN.0000000000000951.

  PMID: 26575144 BACKGROUND

• Su X, Meng ZT, Wu XH, Cui F, Li HL, Wang DX, Zhu X, Zhu SN, Maze M, Ma D. Dexmedetomidine for prevention of delirium in elderly patients after non-cardiac surgery: a randomised, double-blind, placebo-controlled trial. Lancet. 2016 Oct 15;388(10054):1893-1902. doi: 10.1016/S0140-6736(16)30580-3. Epub 2016 Aug 16.

  PMID: 27542303 BACKGROUND

• Reade MC, Eastwood GM, Bellomo R, Bailey M, Bersten A, Cheung B, Davies A, Delaney A, Ghosh A, van Haren F, Harley N, Knight D, McGuiness S, Mulder J, O'Donoghue S, Simpson N, Young P; DahLIA Investigators; Australian and New Zealand Intensive Care Society Clinical Trials Group. Effect of Dexmedetomidine Added to Standard Care on Ventilator-Free Time in Patients With Agitated Delirium: A Randomized Clinical Trial. JAMA. 2016 Apr 12;315(14):1460-8. doi: 10.1001/jama.2016.2707.

  PMID: 26975647 BACKGROUND

• 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.

  PMID: 23963131 BACKGROUND

• Brummel NE, Jackson JC, Pandharipande PP, Thompson JL, Shintani AK, Dittus RS, Gill TM, Bernard GR, Ely EW, Girard TD. Delirium in the ICU and subsequent long-term disability among survivors of mechanical ventilation. Crit Care Med. 2014 Feb;42(2):369-77. doi: 10.1097/CCM.0b013e3182a645bd.

  PMID: 24158172 BACKGROUND

MeSH Terms

Conditions

Sepsis; Delirium

Interventions

Dexmedetomidine; Saline Solution

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Confusion; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Dong-Xin Wang, MD,PhD

  Peking University First Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor and Chairman, Department of Anesthesiology and Critical Care Medicine

Study Record Dates

• First Submitted: May 3, 2021
• First Posted: May 7, 2021
• Study Start: May 28, 2021
• Primary Completion: February 2, 2024
• Study Completion: March 2, 2024
• Last Updated: August 5, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)