Minimizing ICU Neurological Dysfunction With Dexmedetomidine-induced Sleep

Anesthesia Clinical Trial

— MINDDS  

Official title:

Minimizing ICU Neurological Dysfunction With Dexmedetomidine-induced Sleep (MINDDS): A Randomized Placebo-controlled Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02856594
• Other study ID #: 2016P000742
• Secondary ID: 1R01AG053582
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: March 6, 2017
• Est. completion date: February 16, 2022

Study information

• Verified date: February 2023
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 469
• Est. completion date: February 16, 2022
• Est. primary completion date: February 11, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 60 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Anesthesia
• Delirium
• Postoperative Delirium
• Sleep

Intervention

Drug:
• Dexmedetomidine
Dexmedetomidine
• Placebo
Placebo

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Massachusetts General Hospital	National Institute on Aging (NIA)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Length of Hospital Stay	Medical Record Review	from postoperative day 0 until date of hospital discharge (no prespecified length possible)
Primary	Incidence of Delirium	Confusion Assessment Method	Post operative day 1 (24 hours)
Secondary	ICU Delirium/Coma-free Days	Confusion Assessment Method	Up until postoperative day 3, or up until postoperative day 7 or discharge for patients who are delirious beyond postoperative day 5
Secondary	Severity of Delirium	Confusion Assessment Method (CAM): Minimum Score=0, Maximum Score=19, Higher Scores: indicate increased severity of delirium	Up until postoperative day 3, or up until postoperative day 7 or discharge for patients who are delirious beyond postoperative day 5
Secondary	30-day, 90-day, and 180-day Mortality	30-day, 90-day, and 180-day mortality	Up to postoperative day 180 (6 months)
Secondary	Postoperative Cognitive Status	Telephone Montreal Cognitive Assessment (tMoCA): Minimum Score=0, Maximum Score=22, Higher Scores: indicate better cognitive function	30 days, 90 days, and 180 days postoperatively
Secondary	Postoperative Health Related Quality of Life	This included the PROMIS Global Health SF V.1.1, PROMIS Physical Function SF 8b V.1.2, PROMIS Pain Interference SF 8a V.1.0, PROMIS Applied Cognition Abilities SF 8a V.1.0, and PROMIS Sleep Disturbance SF 4A V.1.0, respectively. Scores from each assessment were converted to a T-score for analysis with a mean of 50 and a standard deviation of 10, with lower scores on the PROMIS Pain Interference SF and PROMIS Sleep Disturbance SF considered better, whereas higher scores on all other assessments were considered better.	30 days, 90 days, and 180 days postoperatively
Secondary	Blood Delirium Biomarkers	Blood samples will be taken including whole blood, serum, TruCulture, and PAXgene to assess proteins, DNA, and RNA.	perioperative
Secondary	EEG Delirium Biomarkers	EEG burst suppression and alpha power will be analyzed for association with delirium.	intraoperative