Postoperative DeliriumPhase 2/3MINDDSNCT02856594
Minimizing ICU Neurological Dysfunction With Dexmedetomidine-induced Sleep
A Phase 2/3 study testing Dexmedetomidine in people with Postoperative Delirium and Sleep, run by Massachusetts General Hospital at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 60 years and olderHealthy volunteers can take part
- Conditions the study is for
- Postoperative Delirium, Sleep, Anesthesia
- What is being tested?
- Dexmedetomidine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 469 participants
- Where
- 1 siteUnited States
- Study dates
- 6 Mar 2017to 16 Feb 2022
- Phase
- Phase 2/3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 60 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age ≥ 60
- Scheduled for a cardiac surgical procedure with planned post-operative admission to the CSICU for ≥ 24 hours
- Scheduled same day surgical admission
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Massachusetts General Hospital
Boston, Massachusetts, 02114
About this study
Official title: Minimizing ICU Neurological Dysfunction With Dexmedetomidine-induced Sleep (MINDDS): A Randomized Placebo-controlled Trial
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.
Read the 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.
- Conditions
- Postoperative Delirium, Sleep, Anesthesia
- Being tested
- Dexmedetomidine, Placebo
- Medical subject headings
- Emergence Delirium
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DexmedetomidineDrug
Also called Precedex
Dexmedetomidine
PlaceboDrug
Also called Normal Saline
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Dexmedetomidine-induced sleep | Experimental | Precedex (Dexmedetomidine) intervention: Intravenous administration of 1mcg/kg over 40 minutes. Receives: Drug: Dexmedetomidine |
| Placebo | Placebo comparator | Placebo of normal saline: Intravenous administration of normal saline over 40 minutes. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Delirium
The number of patients with delirium is reported using the Confusion Assessment Method.
Measured: Post operative day 1 (24 hours)
Secondary outcomes (7)
ICU Delirium/Coma-free Days
Confusion Assessment Method
Measured: Up until postoperative day 3, or up until postoperative day 7 or discharge for patients who are delirious beyond postoperative day 5
Severity of Delirium
Confusion Assessment Method (CAM): Minimum Score=0, Maximum Score=19, Higher Scores: indicate increased severity of delirium
Measured: Up until postoperative day 3, or up until postoperative day 7 or discharge for patients who are delirious beyond postoperative day 5
Cumulative 30-day, 90-day, and 180-day Mortality
The number of cumulative deaths occurring at 30-days, 90-days, and 180-days
Measured: Up to postoperative day 180 (6 months)
Postoperative Cognitive Status
Telephone Montreal Cognitive Assessment (tMoCA): Minimum Score=0, Maximum Score=22, Higher Scores: indicate better cognitive function
Measured: 30 days, 90 days, and 180 days postoperatively
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.
Measured: 30 days, 90 days, and 180 days postoperatively
Blood Delirium Biomarkers
Blood samples will be taken including whole blood, serum, TruCulture, and PAXgene to assess proteins, DNA, and RNA.
Measured: perioperative
EEG Delirium Biomarkers
EEG alpha power will be analyzed for association with delirium.
Measured: intraoperative
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Aug 2016 (estimated)
- Study start6 Mar 2017
- Primary completion11 Feb 2022
- Study completion16 Feb 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Postoperative DeliriumStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 469 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Responsible party
- Principal investigator, Oluwaseun Johnson-Akeju, MD, MMSc, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02856594
- Sponsor's protocol ID
- 2016P000742
- Other IDs
- 1R01AG053582
- Acronym
- MINDDS
- Status last verified
- Aug 2026
- First submitted
- 29 Jul 2016
- Last updated
- 1 Sep 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes
Publications
Freedman IG, Boncompte G, Qu JZ, Khawaja ZQ, Turco I, Mueller A, Wiredu K, McKay TB, Westover MB, Pedemonte JC, Akeju O. Anesthesia-induced electroencephalogram oscillations and perioperative outcomes in older adults undergoing cardiac surgery. J Clin Anesth. 2025 Mar;102:111770. doi: 10.1016/j.jclinane.2025.111770. Epub 2025 Feb 7.
PubMed 39921932Wiredu K, Mueller A, McKay TB, Behera A, Shaefi S, Akeju O. Sex Differences in the Incidence of Postoperative Delirium after Cardiac Surgery: A Pooled Analyses of Clinical Trials. Anesthesiology. 2023 Oct 1;139(4):540-542. doi: 10.1097/ALN.0000000000004656. No abstract available.
PubMed 37535937Qu JZ, Mueller A, McKay TB, Westover MB, Shelton KT, Shaefi S, D'Alessandro DA, Berra L, Brown EN, Houle TT, Akeju O; MINDDS Study Team. Nighttime dexmedetomidine for delirium prevention in non-mechanically ventilated patients after cardiac surgery (MINDDS): A single-centre, parallel-arm, randomised, placebo-controlled superiority trial. EClinicalMedicine. 2022 Dec 24;56:101796. doi: 10.1016/j.eclinm.2022.101796. eCollection 2023 Feb.
PubMed 36590787Shelton 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.
PubMed 29678977