Delirium, Postoperative Cognitive Dysfunction
Conditions
Keywords
Postoperative Delirium, Postoperative Cognitive Dysfunction, Rivastigmine, Exelon, Memory impairment, Delirium, Cognitive function
Brief summary
The purpose of this study is to determine whether preoperative administration of Rivastigmine prevents the incidence of postoperative delirium in patients undergoing major surgery as well as postoperative cognitive dysfunction.
Detailed description
Postoperative delirium (POD) and Postoperative cognitive dysfunction (POCD) are common significant postoperative complications in elderly patients. A reduction of postoperative complications would lead to improved functional status, greater independence and reduction in health care cost. Scientific evidence shows that acetylcholinesterase inhibitors may reduce incidence and/or severity of postoperative delirium. We propose to conduct a randomized, double-masked, placebo-controlled study to assess effectiveness of Rivastigmine, an acetylcholinesterase inhibitor. Rivastigmine transdermal system (Exelon Patch) is approved by FDA for the treatment of mild to moderate Alzheimer's dementia and mild to moderate dementia associated with Parkinson's disease. Patients 65 y.o. and older undergoing major elective surgery will qualify for the study based on risk assessment guidelines. Patients screening will include Mini Mental Status Examination (MMSE to assess baseline cognitive function), Hamilton scale (to screen for depression), Telephone Interview of Cognitive Status Modified (TICS-M to assess baseline cognitive function over the phone) and Brief Test of Adult Cognition by Telephone (BTACT to assess baseline cognitive function over the phone). All study subjects will be randomly assigned to one of 2 groups prior to surgery. The treatment group will receive a Rivastigmine patch preoperatively covered by tegaderm dressing and a placebo group will receive just a tegaderm dressing. Both groups will be assessed twice daily at 9am and 4pm for up to 72 hours postoperatively with Confusion Assessment Method for Intensive Care Unit (CAM-ICU), Memorial Delirium Assessment Scale (MDAS) and Mini Mental Status Examination (to diagnose delirium and assess its severity). At one month and three months postoperatively subjects with a postoperative MMSE of 27 or less will be assessed for postoperative cognitive dysfunction. The assessment will be performed over the phone with TICS-M and Brief Test of Adult Cognition by Telephone. Outcomes will be divided into Primary and Secondary outcomes. Primary outcome will determine the proportions of patients with at least one episode of POD in the treatment and placebo groups, diagnosed by CAM-ICU. Secondary outcome will determine the proportions of patients with development of POCD in both groups, diagnosed by TICS-M at 1 month postoperatively. Secondary outcome will also determine cumulative number of POD episodes within first 3 days of hospital stay as diagnosed by CAM-ICU, severity of POD as diagnosed by the MDAS, recovery of cognitive function as diagnosed by MMSE, TICS-M and BTACT, and length of hospital stay.
Interventions
Rivastigmine Patch 4.6 mg/24 hours: 5 cm2 size containing 9 mg rivastigmine applied to upper back preoperatively for a period of 24 hours
OTHERPlacebo Patch
A 2x2 gauze and a Tegaderm dressing applied to upper back within 3 hours of surgery for a period of 24 hours.
Sponsors
Novartis
NYU Langone Health
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
65 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
65 ≥ y.o. undergoing major elective surgery over 2 hours in length with one or more of the following: * Preoperative cognitive impairment * Age \> 70 y.o. * Use of psychoactive medications * History of prior delirium * Severe illness/co-morbidity
Exclusion criteria
* Delirium on admission Profound dementia No spoken/written English An emergent procedure Hypersensitivity to Rivastigmine
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of POD | 72 hours postoperatively | Is the incidence of POD not affected by rivastigmine treatment or not. |
Countries
United States
Participant flow
Recruitment details
Patientsof 65years and older admitted for elective surgery undergeneral anesthesia were screened. Only patients at risk fordeveloping POD were considered for recruitment
Pre-assignment details
This was a randomized, placebo controlled, double-blind clinical trial. Screened patients were 65 years +, having elective surgery under general anesthesia. Only patients at risk for POD were considered for recruitment. Eligible patients received rivastigmine 5cm2 transdermal or placebo patch. 30 patients recruited but only 28 had complete data.
Participants by arm
| Arm | Count |
|---|---|
| Rivastigmine 5-cm2 Transdermal Patch Only patients at risk for developing POD were considered for recruitment. That risk was based on the presence of at least one of five predictive factors: (1) preoperative cognitive impairment (Mini mental state examination (MMSE)\<24); (2) advanced age (\>70 years); (3) preoperative use of psychoactive drugs; (4) history of prior delirium; and/or (5) severe illness or comorbidity. Eligible patients received a rivastigmine 5-cm2 transdermal patch | 11 |
| Placebo Patch Only patients at risk for developing POD were considered for recruitment. That risk was based on the presence of at least one of five predictive factors: (1) preoperative cognitive impairment (Mini mental state examination (MMSE)\<24); (2) advanced age (\>70 years); (3) preoperative use of psychoactive drugs; (4) history of prior delirium; and/or (5) severe illness or comorbidity. Eligible patients received a placebo patch. | 17 |
| Total | 28 |
Baseline characteristics
| Characteristic | Placebo Patch | Rivastigmine 5-cm2 Transdermal Patch | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 17 Participants | 11 Participants | 28 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 72.6471 years STANDARD_DEVIATION 6.52822 | 72.0909 years STANDARD_DEVIATION 5.55796 | 72.4286 years STANDARD_DEVIATION 6.06403 |
| Region of Enrollment United States | 17 participants | 11 participants | 28 participants |
| Sex: Female, Male Female | 10 Participants | 6 Participants | 16 Participants |
| Sex: Female, Male Male | 7 Participants | 5 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 11 | 0 / 17 |
| serious Total, serious adverse events | 0 / 11 | 0 / 17 |
Outcome results
Primary
Incidence of POD
Is the incidence of POD not affected by rivastigmine treatment or not.
Time frame: 72 hours postoperatively
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rivastigmine Patch | Incidence of POD | 2 participants |
| Placebo Patch | Incidence of POD | 4 participants |