Does Nightly Dexmedetomidine Improve Sleep and Reduce Delirium in ICU Patients?

NCT01791296 | Completed Phase 4 DMC

• 1 other identifier: 10053
• Study Type: interventional
• Target: 100
• Locations: 2 countries
• Sites: 2

Brief Summary

Specific Aims

1. 1.Establish the feasibility of larger trial by implementing a sleep protocol in the ICU at 2 different sites. Specifically will be estimating the recruitment rates of patients and the compliance with both interventions.
2. 2.Measure the safety and tolerance of adding night-time sedation with dexmedetomidine using adverse effects and withdrawal rates as indicators.
3. 3.Measure the effect of nocturnal dexmedetomidine on pertinent clinical outcomes and use this outcome data to plan a larger, multicenter trial in this area.

Conditions

Sleep Deprivation; Delirium

Keywords

sedation; sleep; delirium; critical illness; sub-syndromal delirium; intensive care

Outcome Measures

Primary Outcomes (1)

• Development of delirium

  Delirium will be assessed with the ICDSC (Intensive Care Delirium Screening CHecklist) q12h \[Delirium = ICDSC score \>/= 4\]

  participants will be followed for the duration of their ICU stay, an expected average of 5-7 days

Secondary Outcomes (1)

• Development of subsyndromal delirium

  participants will be followed for the duration of ICU stay, an expected average of 5-7 days

Other Outcomes (1)

• Sleep quality

  participants will be followed for the duration of ICU stay, an expected average of 5-7 days

Study Arms (2)

Dexmedetomidine

EXPERIMENTAL

Dexmedetomidine 0.2-0.7 mcg/kg/hr from 21:30 to 6:00

Drug: Dexmedetomidine

Placebo

PLACEBO COMPARATOR

Normal Saline 0.2-0.7 mcg/kg/hr from 21:30 to 6:00

Other: Placebo

Interventions

Dexmedetomidine DRUG

At 21:30h, all current IV sedatives (whether continuous or intermittent) will be decreased by 50% and study drug started at 0.2 mcg/kg/hour at 21h30 to allow sleep between 22h00 and 6h00. Study infusion will be halved at 6:00am and d/c at 6:15am. The infusion rate will be increased by 0.1mcg/kg/hour every 15 minutes when the Riker-SAS is ≥ 4 up to a maximum rate of 0.7 mcg/kg/hr until the targeted sedation goal of a Riker-SAS of 3 is reached. For agitation (ie., Riker-SAS ≥ 5), 'as needed' IV midazolam (1-5 mg IV q1h prn agitation) may be administered during the upwards titration of the study medication. Administration of any dose of as needed IV midazolam will result in the increase of the study medication by 0.1 mcg/kg/hr when ≥ 15 minutes have elapsed since the last upwards titration.

Also known as: Precedex

Dexmedetomidine

Placebo OTHER

At 21:30h, all current IV sedatives (whether continuous or intermittent) will be decreased by 50% and study drug started at 0.2 mcg/kg/hour at 21h30 to allow sleep between 22h00 and 6h00. Study infusion will be halved at 6:00am and d/c at 6:15am. The infusion rate will be increased by 0.1mcg/kg/hour every 15 minutes when the Riker-SAS is ≥ 4 up to a maximum rate of 0.7 mcg/kg/hr until the targeted sedation goal of a Riker-SAS of 3 is reached. For agitation (ie., Riker-SAS ≥ 5), 'as needed' IV midazolam (1-5 mg IV q1h prn agitation) may be administered during the upwards titration of the study medication. Administration of any dose of as needed IV midazolam will result in the increase of the study medication by 0.1 mcg/kg/hr when ≥ 15 minutes have elapsed since the last upwards titration.

Also known as: Normal Saline

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years
• Current expectation on the part of the patient's admitting intensivist for patients to require ICU care for \>/= 48 hrs
• Administered at least one sedative dose (scheduled or prn).

You may not qualify if:

• Patients with delirium (intensive care delirium screening checklist score ≥ 4) or disorientation (not oriented to person and/or place)
• Patients in whom an ICDSC cannot be reliably completed (e.g. primary language is not French or English, baseline severe hearing impairment)
• Inability by one of the investigators to obtain informed consent from the legally authorized representative
• Treating physician refusal
• Heart rate ≤ 50 BPM
• Systolic blood pressure ≤ 90 mmHg despite the administration of norepinephrine ≥ 15 mcg/min and/or vasopressin ≥ 0.04 units/min
• Admission with acute decompensated heart failure
• History of heart block without pacemaker based on hospital admission note.
• Acute alcohol withdrawal based on hospital admission note
• History of end stage liver failure (based on presence of ≥ 1 or more of the following: AST/ALT ≥ 2 times ULN, INR ≥ 2, total bilirubin ≥ 1.5)
• Irreversible brain disease consistent with severe dementia based on hospital admission note
• Pregnancy (all women of child-bearing age will undergo a pregnancy test prior to study enrolment)
• Known allergy or sensitivity to clonidine or dexmedetomidine
• Current treatment with dexmedetomidine
• p. Prognosis considered to be hopeless based on consultation with the ICU admitting physician q. Age ≥80 years r. Currently being managed with a high frequency oscillating mode (HFOV) of mechanical ventilation.

Sponsors & Collaborators

• Maisonneuve-Rosemont Hospital: lead
• Tufts Medical Center: collaborator
• Northeastern University: collaborator

Study Sites (2)

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

Maisonneuve Rosemont Hospital

Montreal, Quebec, H1T 2M4, Canada

Location

Related Publications (2)

• Duprey MS, Devlin JW, Skrobik Y. Is there an association between subjective sleep quality and daily delirium occurrence in critically ill adults? A post hoc analysis of a randomised controlled trial. BMJ Open Respir Res. 2020 Aug;7(1):e000576. doi: 10.1136/bmjresp-2020-000576.

  PMID: 32847946 DERIVED

• Skrobik Y, Duprey MS, Hill NS, Devlin JW. Low-Dose Nocturnal Dexmedetomidine Prevents ICU Delirium. A Randomized, Placebo-controlled Trial. Am J Respir Crit Care Med. 2018 May 1;197(9):1147-1156. doi: 10.1164/rccm.201710-1995OC.

  PMID: 29498534 DERIVED

MeSH Terms

Conditions

Sleep Deprivation; Delirium; Critical Illness

Interventions

Dexmedetomidine; Saline Solution

Condition Hierarchy (Ancestors)

Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Mental Disorders; Confusion; Neurobehavioral Manifestations; Neurocognitive Disorders; Disease Attributes; Pathologic Processes

Intervention Hierarchy (Ancestors)

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

Study Officials

• Yoanna Skrobik, MD

  Université de Montréal

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Blinding for participants, care providers, investigator and outcomes assessor
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Yoanna Skrobik MD FRCP(c), Professor of Medicine, University of Montreal; Lise and Jean Saine critical care chair

Model Details: RCT

Study Record Dates

• First Submitted: February 12, 2013
• First Posted: February 13, 2013
• Study Start: January 1, 2011
• Primary Completion: June 1, 2016
• Study Completion: December 1, 2016
• Last Updated: March 17, 2017

Record last verified: 2017-03

Locations

CA (1); US (1)