Minimizing ICU Neurological Dysfunction With Dexmedetomidine-induced Sleep (MINDDS II) (MINDDS II)

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.

Study Overview

• Status: Recruiting
• Conditions: Delirium
• Intervention / Treatment: Drug: Intravenous Dexmedetomidine; Drug: Sublingual Placebo; Drug: Sublingual Dexmedetomidine; Drug: Intravenous Placebo

• Study Type: Interventional
• Enrollment (Estimated): 1800
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Oluwaseun Johnson-Akeju, MD; Phone Number: 617-726-3030; Email: ojohnsonakeju@partners.org
• Study Contact Backup: Name: Ariel Mueller, MA; Phone Number: 6177269252; Email: almueller@mgh.harvard.edu

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90048
      • Not yet recruiting
      • Cedars-Sinai Medical Center
      • Contact: Abirami Kumaresan, MD
    • San Francisco, California, United States, 94117
      • Not yet recruiting
      • University of California San Francisco
      • Contact: Matthieu Legrand, MD
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Recruiting
      • Northwestern University Feinberg School of Medicine
      • Contact: Charles Hogue, MD
  • Iowa
    • Iowa City, Iowa, United States, 522421320
      • Recruiting
      • University of Iowa Carver College of Medicine
      • Contact: Andrew Feider, MD
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Recruiting
      • University of Maryland School of Medicine
      • Contact: Patrick Odonkor, MD
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital
      • Contact: Amit Bardia, MD
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Beth Israel Deaconess Medical Center
      • Contact: Shahzad Shaefi, MD
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Brigham and Women's Hospital
      • Contact: Oluwaseun Johnson-Akeju, MD
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Not yet recruiting
      • Washington University School of Medicine
      • Contact: Ben Palanca, MD
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • Recruiting
      • University of Nebraska Medical Center
      • Contact: Shaun Thompson, MD
  • New York
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University Medical Center
      • Contact: Vivek Moitra, MD
    • The Bronx, New York, United States, 10467
      • Not yet recruiting
      • Montefiore Medical Center
      • Contact: Matthias Eikermann, MD
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Recruiting
      • Duke University Hospital
      • Contact: Mihai Podgoreanu, MD
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Recruiting
      • Vanderbilt University Medical Center
      • Contact: Frederic T Billings, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Aged 60 years or older
• Scheduled to undergo a cardiac surgical procedure with cardiopulmonary bypass
• Planned postoperative admission to the intensive care unit (ICU)

Exclusion Criteria:

• 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)
• 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Intravenous Dexmedetomidine; Intravenous dexmedetomidine (1 μg/kg over 40 minutes, a maximal dose of 80 μg); Other Names: Intravenous Precedex; Drug: Sublingual Placebo; Inert sublingual film; Other Names: Placebo
Experimental: 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.	Drug: Sublingual Dexmedetomidine; Sublingual dexmedetomidine (120 μg); Other Names: Sublingual Precedex; Drug: Intravenous Placebo; Intravenous placebo of 0.9% saline administered over 40 minutes; Other Names: Placebo
Placebo Comparator: 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.	Drug: Sublingual Placebo; Inert sublingual film; Other Names: Placebo; Drug: Intravenous Placebo; Intravenous placebo of 0.9% saline administered over 40 minutes; Other Names: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Delirium	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.	Postoperative day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Delirium	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.	Postoperative Day 1 to Day 7
Delirium Severity	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.	Postoperative day 1 to day 7
Telephonic Montreal Cognitive Assessment	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.	30, 180 and 365 days
Global Health	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.	30, 180 and 365 days
Pain at Rest and Upon Exertion	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.	Postoperative day 1 to day 7
Opioid and Analgesic Administration	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.	48 hours postoperatively
Hospital Length of Stay	Hospital length of stay will be defined as the number of days after surgery until the time of discharge from the hospital.	Postoperatively until discharge, an average of six days
Intensive Care Unit Length of Stay	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.	Postoperatively until discharge, an average of 24 hours
Readmission	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.	30 days postoperatively
Inpatient Morbidity	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.	30 days postoperatively
Mortality	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.	Postoperatively until discharge, an average of six days, and at 30, 180 and 365 days postoperatively

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Investigators: Principal Investigator: Oluwaseun Johnson-Akeju, MD, Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 6, 2025
• Primary Completion (Estimated): October 31, 2027
• Study Completion (Estimated): March 31, 2029

Study Registration Dates

• First Submitted: December 21, 2023
• First Submitted That Met QC Criteria: December 21, 2023
• First Posted (Actual): January 5, 2024

Study Record Updates

• Last Update Posted (Actual): December 31, 2025
• Last Update Submitted That Met QC Criteria: December 29, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Mental Disorders; Confusion; Neurobehavioral Manifestations; Neurocognitive Disorders; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Delirium; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Central Nervous System Depressants; Sensory System Agents; Analgesics, Non-Narcotic; Analgesics; Neurotransmitter Agents; Hypnotics and Sedatives; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Adrenergic Agents; Dexmedetomidine
• Other Study ID Numbers: 2023P003359

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• 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.: Yes