Delirium
Conditions
Keywords
Delirium, Postoperative confusion, Hip fracture, Long bone fracture
Brief summary
Delirium (acute confusion) is a highly prevalent condition among hospitalized elders with substantial morbidity within the hospital and beyond. Particular patient populations are at high risk for poor outcomes after an episode of delirium. Patients with hip and other long bone fractures are at increased risk of developing delirium (acute confusion) which impedes functional recovery. This is a pilot study to test the tolerability and efficacy of donepezil, a cholinesterase inhibitor medication used commonly in persons with dementia, for the prevention of new or worsening delirium in aged hip and other long-bone fracture patients. Additional purposes involve gathering a small amount of patients' serum to better understand the pathophysiology of delirium in this population. The purposes of this pilot study are to determine: 1) the safety and tolerability a cholinesterase inhibitor medication) in aged hip and long bone fracture patients, 2) To obtain estimates of subject accrual and preliminary estimates of effect size on the development of new delirium symptoms to allow for planning of a larger, definitive trial, 3) To better understand the underlying causes of delirium by examining whether a measure of blood anticholinergic activity relates to the incidence and persistence of delirium symptoms, and 4) To explore the interaction between anticholinergic activity, donepezil therapy, and delirium symptoms.
Interventions
DRUGdonepezil
5 mg each day for 30 days
DRUGPlacebo
Encapsulated cornstarch One capsule daily for 30 days
Sponsors
National Institute on Aging (NIA)
Beth Israel Deaconess Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
70 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* hip or other long bone fracture undergoing operative repair * age of 70 years or older * the ability to communicate effectively in English (including adequate hearing) * residence within a 50 mile radius of the BIDMC * life expectancy 6 months or greater * not currently on cholinesterase inhibitor therapy * not with known hypersensitivity to cholinesterase inhibitors * not a previous study participant or refusal
Exclusion criteria
* patients with sick sinus syndrome or greater than 1st degree AV block without a pacemaker * patients with a pathologic fracture due to metastatic cancer * patients with advanced dementia or total functional dependence.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Delirium Using the CAM Over Time | Baseline, hospital interviews, weeks 2, 4 and 6 | Confusion Assessment Method (CAM)-Measure of the presence or absence of delirium. Requires 1) acute change with fluctuating course, 2) inattention, and either 3) disorganized thinking or 4) altered level of consciousness. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline and MDAS Scores Over Time | Baseline, hospital discharge, weeks 2, 4 and 6 | Measures severity of 10 delirium symptoms items (0 not present, 1 mild, 2 moderate, 3 severe) yielding a total score of 0 to 30, with 30 most severe. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Donepezil : 5 mg Each Day for 30 Days donepezil : 5 mg each day for 30 days | 7 |
| Placebo : Encapsulated Cornstarch Placebo : Encapsulated cornstarch One capsule daily for 30 days | 9 |
| Total | 16 |
Baseline characteristics
| Characteristic | Placebo : Encapsulated Cornstarch | Donepezil : 5 mg Each Day for 30 Days | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 9 Participants | 7 Participants | 16 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 87 years STANDARD_DEVIATION 3.7 | 88 years STANDARD_DEVIATION 5.2 | 87 years STANDARD_DEVIATION 4.5 |
| Region of Enrollment United States | 9 participants | 7 participants | 16 participants |
| Sex: Female, Male Female | 4 Participants | 5 Participants | 9 Participants |
| Sex: Female, Male Male | 5 Participants | 2 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 7 / 7 | 4 / 9 |
| serious Total, serious adverse events | 2 / 7 | 0 / 9 |
Outcome results
Primary
Percentage of Participants With Delirium Using the CAM Over Time
Confusion Assessment Method (CAM)-Measure of the presence or absence of delirium. Requires 1) acute change with fluctuating course, 2) inattention, and either 3) disorganized thinking or 4) altered level of consciousness.
Time frame: Baseline, hospital interviews, weeks 2, 4 and 6
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Donepezil : 5 mg Each Day for 30 Days | Percentage of Participants With Delirium Using the CAM Over Time | hospital interviews | 64 percentage of participants |
| Donepezil : 5 mg Each Day for 30 Days | Percentage of Participants With Delirium Using the CAM Over Time | week 4 | 17 percentage of participants |
| Donepezil : 5 mg Each Day for 30 Days | Percentage of Participants With Delirium Using the CAM Over Time | Week 2 | 43 percentage of participants |
| Donepezil : 5 mg Each Day for 30 Days | Percentage of Participants With Delirium Using the CAM Over Time | week 6 | 50 percentage of participants |
| Donepezil : 5 mg Each Day for 30 Days | Percentage of Participants With Delirium Using the CAM Over Time | basline | 14 percentage of participants |
| Placebo : Encapsulated Cornstarch | Percentage of Participants With Delirium Using the CAM Over Time | week 6 | 50 percentage of participants |
| Placebo : Encapsulated Cornstarch | Percentage of Participants With Delirium Using the CAM Over Time | basline | 44 percentage of participants |
| Placebo : Encapsulated Cornstarch | Percentage of Participants With Delirium Using the CAM Over Time | hospital interviews | 64 percentage of participants |
| Placebo : Encapsulated Cornstarch | Percentage of Participants With Delirium Using the CAM Over Time | Week 2 | 43 percentage of participants |
| Placebo : Encapsulated Cornstarch | Percentage of Participants With Delirium Using the CAM Over Time | week 4 | 43 percentage of participants |
95% CI: [0.4, 2.3]GEE
Secondary
Change From Baseline and MDAS Scores Over Time
Measures severity of 10 delirium symptoms items (0 not present, 1 mild, 2 moderate, 3 severe) yielding a total score of 0 to 30, with 30 most severe.
Time frame: Baseline, hospital discharge, weeks 2, 4 and 6
Population: Based on ability to recruit
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Donepezil : 5 mg Each Day for 30 Days | Change From Baseline and MDAS Scores Over Time | Change at Hospital Discharge | 1.3 units on a scale | Standard Deviation 2.5 |
| Donepezil : 5 mg Each Day for 30 Days | Change From Baseline and MDAS Scores Over Time | Change at week 4 | -1.2 units on a scale | Standard Deviation 3.5 |
| Donepezil : 5 mg Each Day for 30 Days | Change From Baseline and MDAS Scores Over Time | Change at Week 2 | -0.1 units on a scale | Standard Deviation 2.3 |
| Donepezil : 5 mg Each Day for 30 Days | Change From Baseline and MDAS Scores Over Time | Change at week 6 | -0.6 units on a scale | Standard Deviation 2.6 |
| Donepezil : 5 mg Each Day for 30 Days | Change From Baseline and MDAS Scores Over Time | Baseline | 6.3 units on a scale | Standard Deviation 3.4 |
| Placebo : Encapsulated Cornstarch | Change From Baseline and MDAS Scores Over Time | Change at week 6 | -2.0 units on a scale | Standard Deviation 7.5 |
| Placebo : Encapsulated Cornstarch | Change From Baseline and MDAS Scores Over Time | Baseline | 8.4 units on a scale | Standard Deviation 6.5 |
| Placebo : Encapsulated Cornstarch | Change From Baseline and MDAS Scores Over Time | Change at Hospital Discharge | 1.6 units on a scale | Standard Deviation 5.2 |
| Placebo : Encapsulated Cornstarch | Change From Baseline and MDAS Scores Over Time | Change at Week 2 | -2.2 units on a scale | Standard Deviation 4.9 |
| Placebo : Encapsulated Cornstarch | Change From Baseline and MDAS Scores Over Time | Change at week 4 | -2.0 units on a scale | Standard Deviation 6.4 |
95% CI: [-1.5, 1.2]GEE