Delirium
Conditions
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.
Interventions
Intravenous dexmedetomidine (1 μg/kg over 40 minutes, a maximal dose of 80 μg)
Sublingual dexmedetomidine (120 μg)
DRUGIntravenous Placebo
Intravenous placebo of 0.9% saline administered over 40 minutes
Inert sublingual film
Sponsors
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
Countries
United States
Contacts
Primary ContactOluwaseun Johnson-Akeju, MD
Backup ContactAriel Mueller, MA
Outcome results
None listed