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Investigation of Sleep in the Intensive Care Unit (ICU-SLEEP)

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ClinicalTrials.gov Identifier: NCT03355053
Recruitment Status : Recruiting
First Posted : November 28, 2017
Last Update Posted : June 29, 2018
Sponsor:
Collaborator:
National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by (Responsible Party):
Michael Brandon Westover, Massachusetts General Hospital

Tracking Information
First Submitted Date  ICMJE November 22, 2017
First Posted Date  ICMJE November 28, 2017
Last Update Posted Date June 29, 2018
Actual Study Start Date  ICMJE June 1, 2018
Estimated Primary Completion Date April 1, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 22, 2017)
Incidence of delirium [ Time Frame: 7 days ]
incidence of delirium, defined as any positive CAM or CAM-ICU assessment over the first 7 ICU days (Aim 1a), comparing usual care+placebo (n=250) with Dex (combined slow-bolus + low-dose overnight continuous infusion groups, n=500)
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03355053 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 22, 2017)
Incidence of delirium between Dex groups [ Time Frame: 7 days ]
Incidence of delirium within the two Dex treatment subgroups within the first 7 days within the ICU, assessed by the Confusion Assessment Method (CAM) or CAM-ICU.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Investigation of Sleep in the Intensive Care Unit
Official Title  ICMJE Investigation of Sleep in the Intensive Care Unit
Brief Summary Sleep deprivation is common and severe in critically ill patients cared for in intensive care units (ICUs), and is hypothesized to be a key modifiable risk factor for delirium and long-term cognitive disability. Dexmedetomidine reduces the incidence of delirium in ICU patients by unknown mechanisms. This project will determine whether dexmedetomidine reduces delirium by improving sleep, whether bolus dosing vs continuous infusion is better, and the relationship of sleep quality to long-term cognitive outcomes.
Detailed Description Sleep deprivation is among the most common complaints about the ICU experience. ICU sleep tends to be light and non-restorative (as opposed to deep / restorative sleep), severely fragmented, and distributed throughout the day and night rather than consolidated into nighttime hours. Sleep deprived patients suffer from sleep debt, a condition of impaired attention and memory, and cognitive slowing. Sleep disturbances in the ICU arise not only from light and noise pollution, but also from drugs that interfere with brain activity involved in restorative sleep. Sleep deprivation has also been suggested as a major modifiable risk factors for acute encephalopathy, also known as delirium. Delirium is an acute state of confusion that affects up to 80% of ICU patients, and is one of six leading causes of preventable morbidity and mortality in hospitalized elderly patients. Many patients who survive delirium experience long-term cognitive impairment and loss of independence. Current medications used in the ICU to treat sleep problems (e.g. benzodiazepines, antipsychotics) do not induce natural sleep and do not prevent delirium. In contrast, the investigators have found that the α2-adrenoceptor agonist dexmedetomidine can induce biomimetic sleep, a brain state whose pattern of electroencephalogram (EEG) activity, cerebral blood flow, and functional connectivity approximates restorative sleep. Moreover, a recent large clinical trial in post-surgical patients suggests that low-dose dexmedetomidine given overnight substantially reduces the risk of delirium. It is unknown whether this benefit is linked to improved sleep, or whether patients with better sleep while in the ICU have better long-term cognitive outcomes. The investigator's central hypothesis is that sleep deprivation substantially mediates both the short- and long-term cognitive impairments associated with delirium in critical illness. To test this hypothesis, this study is designed to systematically determine 1) the impact of prophylactic dexmedetomidine on sleep quality, 2) the optimal way to give dexmedetomidine (all night vs at the beginning of the night only), 2) the impact of sleep deprivation on short-term cognitive function and delirium, and 3) the contribution of sleep deprivation to long-term neuropsychiatric outcome following critical illness. At the conclusion of these studies, the investigators will have expanded knowledge of sleep physiology in critical illness and relationship of sleep with delirium; evaluated a new preemptive therapeutic strategy to promote sleep and prevent delirium, and developed an understanding of how sleep impacts neuropsychological outcomes after critical illness. These studies will thus will provide crucial guidance for individualized approaches to preserving long-term brain health in this vulnerable patient population.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
phase II, mechanistic, randomized, three-arm parallel group clinical trial
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Condition  ICMJE
  • Delirium
  • Sleep
Intervention  ICMJE Drug: Dexmedetomidine
See description of study arms
Study Arms  ICMJE
  • Active Comparator: Dexmedetomidine (Dex) slow-bolus group

    Study drug will be administered by the patient's nurse. Two 60 mL syringes will be supplied for each patient, containing 50 mL of Dex HCl at 4 ug/ ml Dex HCl or 50 ml normal saline (NS)), depending on randomized assignment. An initial bolus dose will be given over 45 min at 0.33 ml/kg/h (provides 1 mcg/kg/h for Dex patients) at 8PM, followed by continuous overnight infusion at 0.025 ml/kg/h (for Dex patients, provides 0.1 mcg/kg/h), for 7 consecutive nights (or until leaving the ICU), as follows:

    1) Dex slow-bolus group: Dex slow bolus at 8PM over 45 min, then overnight NS until 8AM

    Intervention: Drug: Dexmedetomidine
  • Active Comparator: Dexmedetomidine (Dex) continuous infusion group

    Study drug will be administered by the patient's nurse. Two 60 mL syringes will be supplied for each patient, containing 50 mL of Dex HCl at 4 ug/ ml Dex HCl or 50 ml normal saline (NS)), depending on randomized assignment. An initial bolus dose will be given over 45 min at 0.33 ml/kg/h (provides 1 mcg/kg/h for Dex patients) at 8PM, followed by continuous overnight infusion at 0.025 ml/kg/h (for Dex patients, provides 0.1 mcg/kg/h), for 7 consecutive nights (or until leaving the ICU), as follows:

    2) Dex continuous infusion group: NS slow bolus at 8PM over 45 min, then overnight Dex until 8AM

    Intervention: Drug: Dexmedetomidine
  • Placebo Comparator: Usual care + placebo group

    Study drug will be administered by the patient's nurse. Two 60 mL syringes will be supplied for each patient, containing 50 mL of Dex HCl at 4 ug/ ml Dex HCl or 50 ml normal saline (NS)), depending on randomized assignment. An initial bolus dose will be given over 45 min at 0.33 ml/kg/h (provides 1 mcg/kg/h for Dex patients) at 8PM, followed by continuous overnight infusion at 0.025 ml/kg/h (for Dex patients, provides 0.1 mcg/kg/h), for 7 consecutive nights (or until leaving the ICU), as follows:

    3) NS slow bolus at 8PM over 45 min, then overnight NS until 8AM

    Intervention: Drug: Dexmedetomidine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 22, 2017)
750
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 1, 2023
Estimated Primary Completion Date April 1, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

  1. Admitted to MGH Blake 7 or 12, or Elllison 4 ICU at Massachusetts General Hospital.
  2. Male or female, aged >18 years
  3. Provision of signed and dated informed consent form (by patient or LAR)
  4. Stated willingness to comply with all study procedures and availability for the duration of the study
  5. No on mechanical ventilation at the time of enrollment.
  6. Have not been in the ICU for more than 48 hours before enrollment.
  7. Able to be enrolled before 7PM.
  8. For females of reproductive potential: pregnancy test is negative.

Exclusion Criteria:

An individual who meets any of the following criteria will be excluded from participation in this study:

  1. Mechanical ventilation in the previous 2 months or >5 days in an ICU in the prior month
  2. Unable to be assessed for delirium (e.g. blindness or deafness)
  3. Pregnancy or lactation
  4. Known allergic reactions to components of dexmedetomidine
  5. Follow-up would be difficult (e.g. active substance abuse, homelessness)
  6. Severe dementia, as measured by a score of ≥3.3 on the Short Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE)
  7. Known pre-existing neurologic disease or injury with focal neurologic or cognitive deficits
  8. Serious cardiac disease (e.g. sick sinus syndrome, sinus bradycardia)
  9. Cardiac surgery <3 months ago
  10. Severe liver dysfunction (Child-Pugh class C)
  11. Severe renal dysfunction (receiving dialysis)
  12. Low likelihood of survival >24 hours
  13. Patient is receiving either of the anticholinergic drugs scopolamine or penehyclidine
  14. Concomitant enrollment in another study protocol that may interfere with data acquisition or reliability of measurements;
  15. Deemed unsuitable for selection by the research team or ICU providers due to any medical, legal, social, or interpersonal issues that would either compromise the study or the routine care of patients.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: M Brandon Westover, MD/PhD 617-726-3311 mwestover@mgh.harvard.edu
Contact: Seun Akeju, MD 617-697-2824 oluwaseun.akeju@mgh.harvard.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03355053
Other Study ID Numbers  ICMJE 2017P000090
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Michael Brandon Westover, Massachusetts General Hospital
Study Sponsor  ICMJE Massachusetts General Hospital
Collaborators  ICMJE National Institute of Neurological Disorders and Stroke (NINDS)
Investigators  ICMJE
Principal Investigator: M. Brandon Westover, MD/PhD Massachusetts General Hospital
PRS Account Massachusetts General Hospital
Verification Date June 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP