A randomised controlled trial of phenobarbitone and phenytoin for newly diagnosed epilepsy in adults

ISRCTN	ISRCTN73223855
DOI	https://doi.org/10.1186/ISRCTN73223855
Protocol serial number	KEMRI SCC 786
Sponsor	University of Oxford (UK)
Funder	The Wellcome Trust (UK) (grant ref: 077092)

Submission date: 07/07/2007
Registration date: 17/07/2007
Last edited: 27/06/2008

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Nervous System Diseases

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Not provided at time of registration

Contact information

Prof Charles Newton
Scientific

P.O. Box 230
Kilifi
80108
Kenya

Email	cnewton@kilifi.kemri-wellcome.org

Study information

Primary study design	Interventional
Study design	Open label randomised trial of phenobarbitone versus phenytoin
Secondary study design	Randomised controlled trial
Scientific title
Study acronym	AEPEP
Study objectives	To compare the frequency of side effects of phenobarbitone to those of phenytoin as first line treatment of active convulsive epilepsy.
Ethics approval(s)	The Kemri/National Ethical Review Committee reviewed the proposal, and permission was granted on 21st June 2007 (ref: SSC 786).
Health condition(s) or problem(s) studied	Epilepsy
Intervention	Phenobarbitone versus phenytoin, in which the assessor is blinded to the treatment allocation and patient is given information on the side effects of both anti-epileptic drugs together, but is not aware which side effects is attributed to which drug. Treatment: The following regimens for the drugs will be used: Phenobarbitone: adults will be started on 60 mg daily orally in the evening, increasing to 120 mg daily after two weeks. Thereafter the dose will be titrated according to the response and side effects. If seizures are not controlled (greater than one per week) by six months after enrolling into the trial, the subject will be started on phenytoin. Phenytoin: adults will be started on 50 mg daily, increasing to 100 mg daily (in two doses one in the morning and one in the evening). Thereafter the dose will be titrated according to the response and side effects. If seizures are not controlled (greater than one per week) by six months after enrolling into the trial, the subject will be started on phenobarbitone. If both drugs prove to be ineffective, i.e., continued seizures after substitution with the other study drug then the subject will be started on dual therapy. Monitoring: All subjects will be seen a month after enrolment into the study, when they will be assessed by a clinician and the dosage of the drug adjusted according to clinical response and side effects. Blood and saliva samples will be taken for concentrations of the Antiepileptic Drug (AED), but the results will only be available at the subsequent visit. Thereafter subjects will be seen at 3 months, 6 months and 12 months after starting treatment. At each visit, the subjects will be seen by a fieldworker (blinded to the treatment group), who will administer a Quality Of Life (QOL) questionnaire. Thereafter the subject will be seen by a clinician who will manage the epilepsy according to standard medical practice. Subjects will also be asked to bring in the bottle of tablets so that they can be counted, and the excess tablets will be used to aid in estimation of compliance. Furthermore subjects will be visited at home by a designated fieldworker (maximum of 14 visits per day) to promote adherence.
Intervention type	Drug
Phase	Not Specified
Drug / device / biological / vaccine name(s)	Phenobarbitone, phenytoin
Primary outcome measure(s)	Frequency of side effects.
Key secondary outcome measure(s)	1. Time to next seizure after starting treatment using an epilepsy history questionnaire 2. Seizure frequency: frequency of seizures will be monitored using seizure calendars, which the subjects will be educated on keeping 3. Compliance with drugs: drug compliance will be assessed by direct measurement of drug levels in blood at the initial contact and at 12 months; and using saliva samples at the end of 1, 3, 6 and 12 months. This will be reinforced by tablet counting and information elicited from patients/caregivers 4. Quality of life measure as developed for this proposal 5. Cognitive effects: subjects will have a culturally appropriate test of cognitive function performed at 6 months and 1 and 3 years afterwards
Completion date	31/12/2011

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	Not Specified
Target sample size at registration	300
Key inclusion criteria	Adults (greater than 17 years) with active epilepsy, i.e. two or more seizures within the last year and the following seizure types: 1. Tonic-clonic 2. Partial becoming generalised 3. Partial motor
Key exclusion criteria	1. Subjects who have received antiepileptic drugs in the past 2. Subjects with absence, myoclonic or atonic seizures 3. Subjects with progressive neurological disease 4. Subjects with severe learning difficulties 5. Less than 18 years old
Date of first enrolment	09/07/2007
Date of final enrolment	31/12/2011

Locations

Countries of recruitment

Kenya

Study participating centre

P.O. Box 230

Kilifi
80108
Kenya

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan