E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10012218 |
E.1.2 | Term | Delirium |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To determine whether patients who are treated with 5 mg of donepezil (DPZ) for 7 days after an elective total hip or knee replacement show a reduced incidence of delirium. |
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E.2.2 | Secondary objectives of the trial |
To determine whether:
a) Patients who are treated with 5 mg of DPZ for 7 days after an elective total hip or knee replacement will show a reduction in the severity of delirium.
b) Patients who are treated with 5 mg of DPZ for 7 days after an elective total hip or knee replacement will show a decrease in the duration of delirium.
c) Patients who are treated with 5 mg of DPZ for 7 days after an elective total hip or knee replacement will show a reduction in subsyndromal symptoms and behavioural symptoms associated with delirium.
d) Patients who are treated with 5 mg of DPZ for 7 days after an elective total hip or knee replacement will show less worsening in cognitive functions in both the short and long term.
e) Patients who are treated with 5 mg of DPZ for 7 days after an elective total hip or knee replacement will show a reduction in hospital stay.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion Criteria: • Awaiting elective total hip or knee replacement • 65 years old or over • Valid written informed consent
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E.4 | Principal exclusion criteria |
Exclusion criteria: • Subjects with delirium as defined by the CAM • Subjects undergoing revision/complex hip/knee surgery • Subjects who are deaf, visually impaired or have insufficient English to the extent where they cannot complete the study assessments. • Subjects with moderately severe cognitive impairment at baseline (i.e. MMSE <20) • Subjects with alcohol dependence syndrome (ICD-10 definition) • Subjects with severe nausea and vomiting precluding the use of DPZ • Subjects currently taking cholinesterase inhibitors • Subjects taking antipsychotic/ neuroleptic medication that may mask symptoms of delirium • Hypnotics or anxiolytics initiated less than a month ago • Subjects with a known hypersensitivity to DPZ (piperidine derivatives or any excipients used in its formulation – or that of the placebo) • Severe bladder outflow obstruction Spinal anaesthesia during surgery • Subjects with cardiac problems that contraindicate the prescription of cholinesterase inhibitors: o Sick sinus syndrome o Resting pulse of <50 o Supraventricular conduction defects
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E.5 End points |
E.5.1 | Primary end point(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 7) they develop an episode of delirium. A risk ratio will be calculated. Delirium will be diagnosed using the Confusion Assessment Method (CAM) (Inouye et al. 1990), 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 DSM IV diagnosis of delirium.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 0 |