Donepezil for the prevention of further delayed stroke following brain bleeding

Phase 1

• Conditions: Aneurysmal subarachnoid haemorrhageCerebral vasospasmIschaemic stroke; MedDRA version: 16.0Level: LLTClassification code 10047164Term: Vasospasm cerebralSystem Organ Class: 10029205 - Nervous system disorders; MedDRA version: 16.0Level: PTClassification code 10061256Term: Ischaemic strokeSystem Organ Class: 10029205 - Nervous system disorders; MedDRA version: 16.0Level: LLTClassification code 10055845Term: Haemorrhage subarachnoidSystem Organ Class: 10029205 - Nervous system disorders; Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

• Registration Number: EUCTR2013-002457-30-GB
• Lead Sponsor: St George's University of London

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2013-07-01
• Last Update Posted: 3 April 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

1. Patients aged 18-85 admitted to St George's Hospital neurosurgical service with confirmed aneurysmal subarachnoid haemorrhage (brain bleeding from an aneurysm).
2. Amount of blood: Fisher score = 2 or greater (blood load on CT scan)
3. Able to be enroled within 12-72 hours of brain bleeding symptom onset.
4. Index aneurysm suitable for endovascular occlusion (coiling)
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 76
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 24

Exclusion Criteria

1. Allergy to donepezil or other piperidine derivatives.
2. Pregnancy.
3. Lactating or breast feeding women
4. Male or female participants that are unwilling to use an effective method of birth control (hormonal or barrier method of birth control; abstinence from time consent is signed until 6 weeks after the last dose of Donepezil
5. Known dementia.
6. Severe hepatic impairment (Child-Pugh Class C)
7. Patients with ‘sick sinus syndrome’ or other supraventricular cardiac conduction conditions such as sino-atrial or atrioventricular block.
8. Patients with a history of brittle asthma or obstructive pulmonary disease, requiring regular steroid (inhalers or tablet) for control.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Timepoint(s) of evaluation of this end point: The first XeCT scan is performed under general anaesthetic immediately prior to the administration of the first dose of donepezil. It is expected that this would occur within the first 24 hours after enrolment. The second XeCT scan would be performed as soon as possible after the treatment of the participant's aneurysm (but not less than 3 hours after the first XeCT scan (timescale in protocol: 3-24h).;Main Objective: Does donepezil improve brain blood flow after brain bleeding from aneurysms (subarachnoid haemorrhage)?;Secondary Objective: Is donepezil safe and well tolerated in patients with acute brain bleeding (subarachnoid haemorrhage)?;Primary end point(s): Changes in regional cerebral blood flow (mL/100g/min) measured by two Xenon CT perfusion scans, one performed before the administration of a loading dose of donepezil, and the other after this dose.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): 1. Modified Rankin Score at 6 months. <br>2. Evidence of brain infarction on imaging (CT or MRI) not related to aneurysm occlusion treatment. <br>3. Delayed clinical neurological deficits.<br>4. Number of hospital days.<br>5. Need for endovascular treatment of large vessel spasm<br>;Timepoint(s) of evaluation of this end point: Modified Rankin Score - 6 months after admission.<br><br>All other secondary outcomes would be evaluated during the participant's acute admission for subarachnoid haemorrhage (usually 1-4 weeks).