Minimizing ICU Neurological Dysfunction With Dexmedetomidine-induced Sleep (MINDDS II)
- Conditions
- Delirium
- Interventions
- Drug: Intravenous PlaceboDrug: Sublingual Placebo
- Registration Number
- NCT06192615
- Lead Sponsor
- Massachusetts General Hospital
- Brief Summary
This is a pragmatic phase III, randomized, blinded, double placebo-controlled, three-arm trial of elderly patients following cardiac surgery to assess the relationship between nighttime intravenous (IV) and sublingual dexmedetomidine on postoperative delirium and functional outcomes after surgery.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 1800
- Aged 60 years or older
- Scheduled to undergo a cardiac surgical procedure with cardiopulmonary bypass
- Planned postoperative admission to the intensive care unit (ICU)
- Allergy or hypersensitivity to dexmedetomidine or the placebo study medication
- Preexisting diagnosis of Alzheimer's Disease or Related Dementia, severe cognitive impairment or delirium at baseline
- Severe liver failure (Child-Pugh score > 5)
- History of obstructive sleep apnea
- Severe deficit(s) due to structural or anoxic brain damage
- Undergoing a surgical procedure requiring total circulatory arrest
- SARS-CoV-2 positive or symptomatic (e.g., fever, cough, loss of taste/smell)
- Blind, deaf, or unable to communicate in English
- Patients experiencing circumstances for which long-term follow-up might be difficult (e.g., homelessness, active psychotic disorder, or substance abuse)
- Co-enrollment in other interventional studies that, in the opinion of the site investigator and/or PI, might interfere with study participation, collection, or interpretation of the study data
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Sublingual Dexmedetomidine Sublingual Dexmedetomidine After admission to the ICU and discontinuation of mechanical ventilation, sublingual dexmedetomidine (120 μg) and an intravenous placebo (0.9% saline over 40 minutes) will be administered nightly for the first three nights while the patient is in the intensive care unit. Placebo Sublingual Placebo After admission to the ICU and discontinuation of mechanical ventilation, an intravenous placebo (0.9% saline over 40 minutes) and a sublingual placebo (inert film) will be administered nightly for the first three nights while the patient is in the intensive care unit. Intravenous Dexmedetomidine Sublingual Placebo After admission to the ICU and discontinuation of mechanical ventilation, intravenous dexmedetomidine (1 μg/kg over 40 minutes, a maximal dose of 80 μg) and a sublingual placebo (inert film) will be administered nightly for the first three nights while the patient is in the intensive care unit. Placebo Intravenous Placebo After admission to the ICU and discontinuation of mechanical ventilation, an intravenous placebo (0.9% saline over 40 minutes) and a sublingual placebo (inert film) will be administered nightly for the first three nights while the patient is in the intensive care unit. Intravenous Dexmedetomidine Intravenous Dexmedetomidine After admission to the ICU and discontinuation of mechanical ventilation, intravenous dexmedetomidine (1 μg/kg over 40 minutes, a maximal dose of 80 μg) and a sublingual placebo (inert film) will be administered nightly for the first three nights while the patient is in the intensive care unit. Sublingual Dexmedetomidine Intravenous Placebo After admission to the ICU and discontinuation of mechanical ventilation, sublingual dexmedetomidine (120 μg) and an intravenous placebo (0.9% saline over 40 minutes) will be administered nightly for the first three nights while the patient is in the intensive care unit.
- Primary Outcome Measures
Name Time Method Delirium Postoperative day 1 The primary outcome will be delirium occurring on postoperative day one. Delirium will be assessed using the Confusion Assessment Method (CAM) twice daily. Delirium will be defined as present if either the morning or afternoon assessment are positive for delirium.
- Secondary Outcome Measures
Name Time Method Delirium Severity Postoperative day 1 to day 7 Delirium severity will be assessed using the CAM-Severity (CAM-S) within the first three days following surgery, and separately within the first seven days following surgery. The CAM-S ranges from 0 (no delirium features) to 19, with higher scores indicating worsening delirium severity.
Global Health 30, 180 and 365 days Global health will be assessed at 30, 180 and 365 days using the Patient Reported Outcome Measurement Information System (PROMIS) 29 Profile version 2.1. This assessment results in several subscale scores, each reported as a t-score.
Pain at Rest and Upon Exertion Postoperative day 1 to day 7 Pain will be assessed within the first seven days following surgery, using a trajectory of pain scores at rest and upon exertion/deep breathing. Pain scores will be elicited from patients daily using the Pain Numeric Rating Scale.
Opioid and Analgesic Administration 48 hours postoperatively Outcomes for opioid administration will evaluate the (a) frequency and (b) total consumption, defined as morphine equivalents, in the first 24 and 48 hours postoperatively. These will be captured based off medical record review.
Inpatient Morbidity 30 days postoperatively Major cardiac events will be evaluated within 30 days postoperatively and include stroke, atrial fibrillation and renal failure. These outcomes will be assessed using the Society for Thoracic Surgery database and medical record review.
Delirium Postoperative Day 1 to Day 7 Postoperative delirium will also be assessed as a secondary outcome assessed within the first three days after surgery, and separately within the first seven days following surgery. Delirium will be assessed using the CAM in the same fashion as the primary outcome. In the event the patient is reintubated the CAM-ICU may also be used to assess for postoperative delirium as a secondary outcome.
Intensive Care Unit Length of Stay Postoperatively until discharge, an average of 24 hours Intensive Care Unit (ICU) length of stay will be calculated as the time from discharge from the initial index ICU stay minus the time of admission into the cardiovascular ICU and will be reported in hours.
Telephonic Montreal Cognitive Assessment 30, 180 and 365 days Global cognitive function will be assessed with the T-MoCA in-hospital and at three time points after hospital discharge. Different versions of the T-MOCA will be administered at each time point to minimize learning effects. The T-MoCA ranges from 0 (worst) to 22 (best) points, does not require visual cues or writing, and importantly, can be administered over the phone.
Readmission 30 days postoperatively Hospital readmission will be evaluated within the first 30 days postoperatively using the Society for Thoracic Surgery database or via patient report during follow up phone calls.
Hospital Length of Stay Postoperatively until discharge, an average of six days Hospital length of stay will be defined as the number of days after surgery until the time of discharge from the hospital.
Mortality Postoperatively until discharge, an average of six days, and at 30, 180 and 365 days postoperatively All-cause mortality will be assessed in-hospital and at 30, 180 and 365 days postoperatively. Mortality will be assessed using a combination of electronic medical record review, Society for Thoracic Surgery database, and family report during the follow up phone calls.
Trial Locations
- Locations (12)
Northwestern University Feinberg School of Medicine
🇺🇸Chicago, Illinois, United States
University of Iowa Carver College of Medicine
🇺🇸Iowa City, Iowa, United States
University of Maryland School of Medicine
🇺🇸Baltimore, Maryland, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Brigham and Women's Hospital
🇺🇸Boston, Massachusetts, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
Montefiore Medical Center
🇺🇸Bronx, New York, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
Duke University Hospital
🇺🇸Durham, North Carolina, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States