Clinical trial NCT02856594: Minimizing ICU Neurological Dysfunction With Dexmedetomidine-induced Sleep
Official title: Minimizing ICU Neurological Dysfunction With Dexmedetomidine-induced Sleep (MINDDS): A Randomized Placebo-controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Postoperative Delirium
Sleep
Anesthesia
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: National Institute on Aging (NIA)
First posted: 2016-08-05
Enrollment: 469
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study aims to determine whether, compared with placebo, the nighttime administration of a intravenous dexmedetomidine is effective at inducing sleep and preventing postoperative delirium in extubated post-cardiac surgical patients.

Detailed description: Delirium is an acute brain dysfunction characterized by disturbances in attention, awareness, and cognition not explained by a preexisting neurocognitive disorder. Although the increased mortality rates ascribed to delirium remain debatable, delirium remains a leading cause of preventable morbidity in hospitalized elderly patients. It is also associated with prolonged hospitalization, prolonged institutionalization, and long-term cognitive deficits. Patients with pre-existing dementia, such as Alzheimer's disease, are especially vulnerable to developing delirium. The total healthcare cost attributable to delirium is estimated between $143 and $152 billion annually. In the United States, delirium occurs in approximately 80% of critically ill patients admitted to medical/surgical intensive care units (ICU), and 15% of patients admitted to cardiac surgical (CS) ICU. Most patients diagnosed with delirium also present with multiple comorbidities (sepsis, multi-organ failure) that significantly confound our understanding of this disease. Thus, to date, no pharmacological intervention to treat delirium has been identified.

There is mounting evidence to suggest that sleep deprivation may be a modifiable risk factor for the development of delirium. Presently, pharmacological treatment with no current medication (benzodiazepines, antipsychotics) induces natural sleep or reliably reduces the incidence of delirium. The investigators have found that biomimetic sleep, defined here as pharmacological induction of rapid eye movement sleep (REM) and non-REM (N1, N2, N3) sleep states using dexmedetomidine, can now be achieved in humans. The overall objective of this study is to evaluate the efficacy of biomimetic sleep in reducing the incidence and severity of delirium in extubated CSICU patients. The investigators will also assess for peri-operative electroencephalogram biomarkers of delirium, and the association between delirium and chronic neuroinflammation using positron emission tomography. The MINDDS study is poised to enable therapeutic and diagnostic discoveries to aid the care of elderly patients who are at risk for developing postoperative delirium.

Eligibility criteria: Inclusion Criteria:

* Age ≥ 60
* Scheduled for a cardiac surgical procedure with planned post-operative admission to the CSICU for ≥ 24 hours
* Scheduled same day surgical admission

Exclusion Criteria:

* Blind, deafness or the inability to speak English
* Greater than 2 days of ICU admission in the month preceding the current surgical procedure
* Renal and liver failure requiring dialysis or Child-Pugh score \> 5
* Follow-up difficulties (i.e. active substance abuse, psychotic disorder, homelessness)
* Previous cardiac surgery within 1 year of surgical procedure
* Allergy to dexmedetomidine
* Chronic therapy with benzodiazepines and/or antipsychotics
* Severe deficit due to structural or anoxic brain damage
* Surgical procedure requiring total circulatory arrest

Objective Drop Criteria

* Scheduled for a second surgical procedure during hospital stay
* Post-operative intubation \> 12 hours

Primary outcomes:
measure: Incidence of Delirium
timeFrame: Post operative day 1 (24 hours)
Secondary outcomes:
measure: ICU Delirium/Coma-free Days
timeFrame: Up until postoperative day 3, or up until postoperative day 7 or discharge for patients who are delirious beyond postoperative day 5
measure: Severity of Delirium
timeFrame: Up until postoperative day 3, or up until postoperative day 7 or discharge for patients who are delirious beyond postoperative day 5
measure: 30-day, 90-day, and 180-day Mortality
timeFrame: Up to postoperative day 180 (6 months)
measure: Postoperative Cognitive Status
timeFrame: 30 days, 90 days, and 180 days postoperatively
measure: Postoperative Health Related Quality of Life
timeFrame: 30 days, 90 days, and 180 days postoperatively
measure: Blood Delirium Biomarkers
timeFrame: perioperative
measure: EEG Delirium Biomarkers
timeFrame: intraoperative
Other outcomes:
measure: Length of Hospital Stay
timeFrame: from postoperative day 0 until date of hospital discharge (no prespecified length possible)
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
References:
citation: Shelton KT, Qu J, Bilotta F, Brown EN, Cudemus G, D'Alessandro DA, Deng H, DiBiasio A, Gitlin JA, Hahm EY, Hobbs LE, Houle TT, Ibala R, Loggia ML, Pavone KJ, Shaefi S, Tolis G, Westover MB, Akeju O. Minimizing ICU Neurological Dysfunction with Dexmedetomidine-induced Sleep (MINDDS): protocol for a randomised, double-blind, parallel-arm, placebo-controlled trial. BMJ Open. 2018 Apr 20;8(4):e020316. doi: 10.1136/bmjopen-2017-020316.