A phase III, seven-day randomised, double-blind, placebo-controlled, parallel group study to assess efficacy of Donepezil for reducing the incidence and severity of Post-Operative Delirium after an elective total hip or knee replacement in patients over 65 years old

ISRCTN	ISRCTN55655483
DOI	https://doi.org/10.1186/ISRCTN55655483
Protocol serial number	DPOD III
Sponsor	Imperial College London (UK)
Funder	Eisai Europe Ltd (UK)

Submission date: 01/06/2007
Registration date: 12/06/2007
Last edited: 12/09/2008

Recruitment status: Stopped
Overall study status: Stopped
Condition category: Surgery

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Craig Ritchie
Scientific

Department of Psychological Medicine
Division of Neurosciences and Mental Health
Imperial College London
Claybrook Centre
Charing Cross Campus
St Dunstan's Road
London
W6 8RP
United Kingdom

Study information

Primary study design	Interventional
Study design	Double-blind, parallel group, single-centre study of seven days of post-operative donepezil or placebo after an elective total hip or knee replacement in patients over 65 years old
Secondary study design	Randomised controlled trial
Scientific title
Study acronym	DPOD III
Study objectives	Patients who are treated with 5 mg of Donepezil (DPZ) for seven days after an elective total hip or knee replacement will show a reduced incidence of delirium. Please note that this trial record was updated on 12/09/2008. As of this update date, the start date of the trial was updated (initial anticipated start date: 09/07/2007); due to several changes of sponsor, the study has been delayed and is currently on temporary hold. Estimated completion date is now December 2009 (initial anticipated end date: 30/06/2008). The initial sponsor was University College London Clinical Research Management Centre (UCL CRMC) (UK) and the sponsorship is currently being transferred to Imperial College London.
Ethics approval(s)	Charing Cross Research Ethics Committee granted approval on the 25th July 2007 (ref: 07/Q0411/61)
Health condition(s) or problem(s) studied	Post-operative delirium
Intervention	5 mg of donepezil (DPZ) or matched placebo once daily for seven days.
Intervention type	Drug
Phase	Phase III
Drug / device / biological / vaccine name(s)	Donepezil
Primary outcome measure(s)	The primary endpoint of the study will be the incidence of post-operative delirium. Patients will be considered as a case of delirium if at any point during the course of follow up (to Day seven) they develop an episode of delirium. A risk ratio will be calculated. Delirium will be diagnosed using the Confusion Assessment Method (CAM) as the primary outcome variable. This is the most widely used instrument for the detection of delirium in the acute hospital setting. It has a sensitivity of 94-100% and a specificity of 90-95% and generates a Diagnostic and Statistical Manual of mental disorders - Fourth Edition (DSM IV) diagnosis of delirium.
Key secondary outcome measure(s)	1. The severity of delirium: severity of delirium will be measured by the Delirium Symptom Index (DSI) post- operatively twice a day (morning and afternoon) up to day six. The DSI is a seven item clinician rated scale which measures the severity of delirium and is sensitive to change. It has good internal consistency and inter-rater reliability 2. Length of delirium: this will be measured as the total number of days on which a patient achieves DSM IV caseness for delirium using the CAM. It will be considered that the patient has had delirium that day if either of the two assessments in a 24-hour period were positive for delirium 3. Presence of subsyndromal delirium and behavioural symptoms: this will be measured using the CAM and be defined as any symptoms of new disorientation, disturbance of attention or perceptual or behavioural disturbance that do not meet the full criteria for delirium 4. Changes in cognition: the Mini-Mental State Examination (MMSE) will be used post- operatively once a day (morning up to day six). This is the most widely used screening test for cognitive impairment. It has a maximum score of 30 and assesses a range of cognitive skills. The MMSE has high inter-rater reliability (0.8) 5. Length of hospital stay: this outcome will indicate whether delirium prophylaxis using DPZ may have health economic benefits. Length of hospital stay will be measured in days
Completion date	01/12/2009
Reason abandoned (if study stopped)	This trial is currently on temporary hold due to changes with the sponsor.

Eligibility

Participant type(s)	Patient
Age group	Senior
Sex	Not Specified
Target sample size at registration	300
Key inclusion criteria	1. Awaiting elective total hip or knee replacement 2. 65 years old or over 3. Valid written informed consent
Key exclusion criteria	1. Subjects with delirium as defined by the Confusion Assessment Method (CAM) 2. Subjects undergoing revision/complex hip/knee surgery 3. Subjects who are deaf, visually impaired or have insufficient English to the extent where they cannot complete the study assessments 4. Subjects with moderately severe cognitive impairment at baseline (i.e. Mini Mental State Examination [MMSE] less than 20) 5. Subjects with alcohol dependence syndrome (International Classification of Diseases [ICD-10] definition) 6. Subjects with severe nausea and vomiting precluding the use of DPZ 7. Subjects currently taking cholinesterase inhibitors 8. Subjects taking antipsychotic/neuroleptic medication that may mask symptoms of delirium 9. Hypnotics or anxiolytics initiated less than a month ago 10. Subjects with a known hypersensitivity to DPZ (piperidine derivatives or any excipients used in its formulation or that of the placebo) 11. Severe bladder outflow obstruction 12. Spinal anaesthesia during surgery 13. Subjects with cardiac problems that contraindicate the prescription of cholinesterase inhibitors: 13.1. Sick sinus syndrome 13.2. Resting pulse of less than 50 13.3. Supraventricular conduction defects
Date of first enrolment	20/03/2008
Date of final enrolment	01/12/2009

Locations

Countries of recruitment

United Kingdom
England

Study participating centre

Department of Psychological Medicine

London
W6 8RP
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan