Condition category
Surgery
Date applied
01/06/2007
Date assigned
12/06/2007
Last edited
12/09/2008
Prospective/Retrospective
Prospectively registered
Overall trial status
Stopped
Recruitment status
Stopped

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Dr Craig Ritchie

ORCID ID

Contact details

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

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

DPOD III

Study information

Scientific title

Acronym

DPOD III

Study hypothesis

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

Charing Cross Research Ethics Committee granted approval on the 25th July 2007 (ref: 07/Q0411/61)

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

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Condition

Post-operative delirium

Intervention

5 mg of donepezil (DPZ) or matched placebo once daily for seven days.

Intervention type

Drug

Phase

Phase III

Drug names

Donepezil

Primary outcome measures

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.

Secondary outcome measures

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

Overall trial start date

20/03/2008

Overall trial end date

01/12/2009

Reason abandoned

This trial is currently on temporary hold due to changes with the sponsor.

Eligibility

Participant inclusion criteria

1. Awaiting elective total hip or knee replacement
2. 65 years old or over
3. Valid written informed consent

Participant type

Patient

Age group

Senior

Gender

Not Specified

Target number of participants

300 randomised

Participant 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

Recruitment start date

20/03/2008

Recruitment end date

01/12/2009

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Department of Psychological Medicine
London
W6 8RP
United Kingdom

Sponsor information

Organisation

Imperial College London (UK)

Sponsor details

Faculty of Medicine
G02 Sir Alexander Fleming Building
South Kensington Campus
London
SW7 2AZ
United Kingdom

Sponsor type

University/education

Website

http://www.imperial.ac.uk

Funders

Funder type

Industry

Funder name

Eisai Europe Ltd (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes