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 |
| Secondary identifying numbers | DPOD III |
- 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
Not provided at time of registration
Contact information
Dr Craig Ritchie
Scientific
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
| 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 |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Scientific title | |
| Study 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(s) | Charing Cross Research Ethics Committee granted approval on the 25th July 2007 (ref: 07/Q0411/61) |
| Condition | Post-operative delirium |
| Intervention | 5 mg of donepezil (DPZ) or matched placebo once daily for seven days. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase III |
| Drug / device / biological / vaccine name(s) | Donepezil |
| Primary outcome measure | 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 study start date | 20/03/2008 |
| Overall study end 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 number of participants | 300 randomised |
| Participant inclusion criteria | 1. Awaiting elective total hip or knee replacement 2. 65 years old or over 3. Valid written informed consent |
| 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
- England
- United Kingdom
Study participating centre
Department of Psychological Medicine
London
W6 8RP
United Kingdom
W6 8RP
United Kingdom
Sponsor information
Imperial College London (UK)
University/education
University/education
Faculty of Medicine
G02 Sir Alexander Fleming Building
South Kensington Campus
London
SW7 2AZ
England
United Kingdom
| Website | http://www.imperial.ac.uk |
|---|---|
"ROR" |
https://ror.org/041kmwe10 |
Funders
Funder type
Industry
Eisai Europe Ltd (UK)
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
