Clinical Trial Results:
An open label randomised controlled trial investigating the effect of donepezil on regional cerebral blood flow in adults with aneurysmal subarachnoid haemorrhage.
Summary
|
|
EudraCT number |
2013-002457-30 |
Trial protocol |
GB |
Global end of trial date |
10 Nov 2016
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
02 Dec 2019
|
First version publication date |
02 Dec 2019
|
Other versions |
|
Summary report(s) |
End of Trial Form |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
Trial identification
|
|||
Sponsor protocol code |
13.0099
|
||
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
|
|||
Sponsor organisation name |
St Georges University of London
|
||
Sponsor organisation address |
Cranmer Terrace, London, United Kingdom, SW17 0QT
|
||
Public contact |
Dr Jeremy B Madigan, St George's Univeristy of London, 0044 02087254481, jeremy.madigan@nhs.net
|
||
Scientific contact |
Dr Jeremy B Madigan, St George's Univeristy of London, 0044 02087254481, jeremy.madigan@nhs.net
|
||
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
10 Nov 2016
|
||
Is this the analysis of the primary completion data? |
Yes
|
||
Primary completion date |
10 Nov 2016
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
10 Nov 2016
|
||
Was the trial ended prematurely? |
Yes
|
||
General information about the trial
|
|||
Main objective of the trial |
To measure the effects of donepezil on regional cerebral blood flow following aneurysmal subarachnoid haemorrhage
Secondary objectives
To assess whether the administration of donepezil to study participants with acute SAH:
I. Is safe.
II. Is tolerable for 21 days.
|
||
Protection of trial subjects |
The data monitoring committee will review the following trial data after the enrolment of the first 10 participants, and for every 20 participants in the trial after that.
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
01 Jul 2013
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
Yes
|
||
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
United Kingdom: 19
|
||
Worldwide total number of subjects |
19
|
||
EEA total number of subjects |
19
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
13
|
||
From 65 to 84 years |
6
|
||
85 years and over |
0
|
|
|||||||||||||||||||
Recruitment
|
|||||||||||||||||||
Recruitment details |
- | ||||||||||||||||||
Pre-assignment
|
|||||||||||||||||||
Screening details |
Clinical history and examination as part of routine care, including medication and allergy history. Plain CT head and CT Angiogram. Bloods: Urea & electrolytes, liver function tests. Pregnancy test for potential female participants with child-bearing potential. | ||||||||||||||||||
Pre-assignment period milestones
|
|||||||||||||||||||
Number of subjects started |
19 | ||||||||||||||||||
Number of subjects completed |
19 | ||||||||||||||||||
Period 1
|
|||||||||||||||||||
Period 1 title |
Overall trial (overall period)
|
||||||||||||||||||
Is this the baseline period? |
Yes | ||||||||||||||||||
Allocation method |
Randomised - controlled
|
||||||||||||||||||
Blinding used |
Not blinded | ||||||||||||||||||
Blinding implementation details |
Neuroradiologist blinded to primary endpoint
|
||||||||||||||||||
Arms
|
|||||||||||||||||||
Are arms mutually exclusive |
Yes
|
||||||||||||||||||
Arm title
|
Donepezil | ||||||||||||||||||
Arm description |
- | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
Donepezil
|
||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||
Other name |
|||||||||||||||||||
Pharmaceutical forms |
Tablet
|
||||||||||||||||||
Routes of administration |
Oral use
|
||||||||||||||||||
Dosage and administration details |
To those randomised to the donepezil arm, the first dose will be a loading dose of 20mg donepezil in suspension given via nasogastric tube under general anaesthesia. Subsequent doses will be 5mg donepezil once daily given orally by either dissolving or dispersing on the tongue or administered via a nasogastric tube, depending on the conscious level and safety of swallow for each participant. Doses should be taken at the same time each day preferably in the evening. All trial participants will receive donepezil for a total of 21 days, to cover the vasospasm ‘at risk’ period.
|
||||||||||||||||||
Arm title
|
Control | ||||||||||||||||||
Arm description |
- | ||||||||||||||||||
Arm type |
No intervention | ||||||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
|
||||||||||||||||||
|
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
Baseline characteristics reporting groups
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Overall trial
|
|||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
End points reporting groups
|
|||
Reporting group title |
Donepezil
|
||
Reporting group description |
- | ||
Reporting group title |
Control
|
||
Reporting group description |
- |
|
|||||||||
End point title |
Mean cerebral blood flow (mL/100g/min [1] [2] | ||||||||
End point description |
Xenon CT Perfusion scans
|
||||||||
End point type |
Primary
|
||||||||
End point timeframe |
At least 3 hours following the first 20mg loading dose of Donepezil
|
||||||||
Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The analysis was not reported due to low number of recruited patients. [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The analysis was not reported due to low number of recruited patients. |
|||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||
Adverse events information [1]
|
|||
Timeframe for reporting adverse events |
To report Serious Adverse Events to Sponsor within 24 hours of notification. All Adverse Events to be recorded on Adverse Event log.
|
||
Assessment type |
Systematic | ||
Dictionary used for adverse event reporting
|
|||
Dictionary name |
MedDRA | ||
Dictionary version |
0
|
||
Frequency threshold for reporting non-serious adverse events: 0% | |||
Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: See adverse events attached. |
|
|||||||
Substantial protocol amendments (globally) |
|||||||
Were there any global substantial amendments to the protocol? Yes | |||||||
Date |
Amendment |
||||||
07 Aug 2013 |
Concerns were raised by the REC about the safety of the single 20mg Donepezil dose, the protocol has been amended such that an interim analysis will be performed by a data monitoring committee after enrolment of the first 10 participants. This will be to investigate the occurrence of defined adverse events in relation to donepezil administration. |
||||||
09 Apr 2014 |
Addition of Exclusion criteria 5.2 for requirement of FiO2 > 0.6 within protocol
Additional section within protocol added 8.7.2.1 ‘technical criteria for participant replacement’
Additional section added within protocol 8.7.2.2 ‘ Clinical criteria for participant replacement’
|
||||||
12 Dec 2014 |
Removal of CT angiogram performed following aneurysm coiling |
||||||
22 Sep 2015 |
Temporary Halt |
||||||
Interruptions (globally) |
|||||||
Were there any global interruptions to the trial? Yes | |||||||
|
|||||||
Limitations and caveats |
|||||||
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||||||
None reported |