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

NCT ID: NCT01791296

Last Updated: 2017-03-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-01-31
• Study Completion Date: 2016-12-31

Brief Summary

Specific Aims

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. Measure the safety and tolerance of adding night-time sedation with dexmedetomidine using adverse effects and withdrawal rates as indicators.

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.

The goal of this study is to determine whether a night-time protocol that incorporates a pharmacologic intervention associated with improved sleep (i.e. dexmedetomidine) will improve sleep quality and reduce the incidence of delirium and sub-syndromal delirium in critically ill patients.

Detailed Description

The goal of this study is to determine whether a nocturnal protocol that incorporates a pharmacologic intervention associated with improved sleep (i.e. dexmedetomidine) will improve sleep quality and reduce the incidence of delirium and sub-syndromal delirium in critically ill patients where ventilator settings have been optimized to optimize sleep quality.

1. To evaluate the impact of a dexmedetomidine-focussed nocturnal sleep protocol that minimizes arousal from sleep on:

1. incidence of delirium [Intensive Care Delirium Screening Checklist (ICDSC) score ≥ 4]

2. incidence of sub-syndromal delirium (ICDSC score 1-3)

3. outcomes specifically defined by place of discharge from hospital (i.e., home,rehabilitation, or long-term care)

2. To gain an understanding of the effect of night-time sedation with dexmedetomidine on:

1. patient safety

2. self-reported sleep quality

3. sleep quality and architecture [based on a subgroup of 10 patients at Tufts Medical Center who will be evaluated using polysomnography(PSG) for one night]

4. time spent within targeted sedation goal

5. time spent without pain

6. agitation-related events

7. length of stay in the ICU

8. duration of mechanical ventilation

9. length of hospital stay

10. total health care costs by measuring medication costs and hospitalization costs, as well as calculating effectiveness (sleep, sedation and pain management vs. cost).

This multicenter study will be performed at:

1. Hopital Maissonneuve Rosemont, Montreal, PQ

2. Tufts Medical Center, Boston, MA

Conditions

Sleep Deprivation; Delirium

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Dexmedetomidine

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

Group Type: EXPERIMENTAL

Dexmedetomidine

Intervention Type: 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.

Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: 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.

Interventions

Dexmedetomidine

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.

Intervention Type: DRUG

Placebo

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.

Intervention Type: OTHER

Other Intervention Names

Precedex; Normal Saline

Eligibility Criteria

Inclusion Criteria

1. Age ≥ 18 years

2. Current expectation on the part of the patient's admitting intensivist for patients to require ICU care for >/= 48 hrs

3. Administered at least one sedative dose (scheduled or prn).

Exclusion Criteria

1. Patients with delirium (intensive care delirium screening checklist score ≥ 4) or disorientation (not oriented to person and/or place)

2. Patients in whom an ICDSC cannot be reliably completed (e.g. primary language is not French or English, baseline severe hearing impairment)

3. Inability by one of the investigators to obtain informed consent from the legally authorized representative

4. Treating physician refusal

5. Heart rate ≤ 50 BPM

6. Systolic blood pressure ≤ 90 mmHg despite the administration of norepinephrine ≥ 15 mcg/min and/or vasopressin ≥ 0.04 units/min

7. Admission with acute decompensated heart failure

8. History of heart block without pacemaker based on hospital admission note.

9. Acute alcohol withdrawal based on hospital admission note

10. 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)

11. Irreversible brain disease consistent with severe dementia based on hospital admission note

12. Pregnancy (all women of child-bearing age will undergo a pregnancy test prior to study enrolment)

13. Known allergy or sensitivity to clonidine or dexmedetomidine

14. 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Tufts Medical Center

OTHER

Sponsor Role: collaborator

Northeastern University

OTHER

Sponsor Role: collaborator

Maisonneuve-Rosemont Hospital

OTHER

Sponsor Role: lead

Responsible Party

Yoanna Skrobik

Yoanna Skrobik MD FRCP(c), Professor of Medicine, University of Montreal; Lise and Jean Saine critical care chair

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Yoanna Skrobik, MD

Role: PRINCIPAL_INVESTIGATOR

Université de Montréal

Locations

Tufts Medical Center

Boston, Massachusetts, United States

Maisonneuve Rosemont Hospital

Montreal, Quebec, Canada

Countries

United States; Canada

References

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.

Reference Type: DERIVED

PMID: 32847946 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 29498534 (View on PubMed)

Other Identifiers

10053

Identifier Type: -

Identifier Source: org_study_id