Supporting the Health of Adults Undergoing Orthopedic Surgery During the Recovery Period (SHARP)

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.

Study Overview

• Status: Completed
• Conditions: Delirium
• Intervention / Treatment: Drug: donepezil; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 70 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 2	Drug: Placebo; Encapsulated cornstarch One capsule daily for 30 days
Active Comparator: 1	Drug: donepezil; 5 mg each day for 30 days; Other Names: Aricept

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline, hospital interviews, weeks 2, 4 and 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline, hospital discharge, weeks 2, 4 and 6

Collaborators and Investigators

• Sponsor: Beth Israel Deaconess Medical Center
• Collaborators: National Institute on Aging (NIA)
• Investigators: Principal Investigator: Edward R Marcantonio, MD, Beth Israel Deaconess Medical Center

Publications and helpful links

General Publications

• Marcantonio ER, Palihnich K, Appleton P, Davis RB. Pilot randomized trial of donepezil hydrochloride for delirium after hip fracture. J Am Geriatr Soc. 2011 Nov;59 Suppl 2(Suppl 2):S282-8. doi: 10.1111/j.1532-5415.2011.03691.x.

Study record dates

Study Major Dates

• Study Start: January 1, 2007
• Primary Completion (Actual): February 1, 2013
• Study Completion (Actual): February 1, 2013

Study Registration Dates

• First Submitted: December 21, 2007
• First Submitted That Met QC Criteria: December 21, 2007
• First Posted (Estimate): January 4, 2008

Study Record Updates

• Last Update Posted (Estimate): August 22, 2014
• Last Update Submitted That Met QC Criteria: August 21, 2014
• Last Verified: August 1, 2014

More Information

Terms related to this study

• Keywords: Delirium; Hip fracture; Postoperative confusion; Long bone fracture
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Neurologic Manifestations; Confusion; Neurobehavioral Manifestations; Neurocognitive Disorders; Delirium; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Enzyme Inhibitors; Nootropic Agents; Cholinesterase Inhibitors; Donepezil
• Other Study ID Numbers: 2006p-000193; R21AG027549 (U.S. NIH Grant/Contract)