A randomised double-blind placebo-controlled trial of Fosphenytoin for prevention of seizures in children with acute non-traumatic encephalopathies

ISRCTN	ISRCTN11862726
DOI	https://doi.org/10.1186/ISRCTN11862726
Protocol serial number	SSC 819
Sponsor	University College London (UK)
Funder	Wellcome Trust

Submission date: 11/01/2005
Registration date: 22/07/2005
Last edited: 06/02/2015

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Signs and Symptoms

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

Dr Charles Newton
Scientific

Neurosciences Unit
Mecklenburgh Square
University College London
London
WC1N 2AP
United Kingdom

Phone	+44 (0)20 7837 7618
Email	cnewton@ich.ucl.ac.uk

Study information

Primary study design	Interventional
Study design	Randomised controlled trial
Secondary study design	Randomised controlled trial
Scientific title	A randomised double-blind placebo-controlled trial of Fosphenytoin for prevention of seizures in children with acute non-traumatic encephalopathies
Study acronym	FOSCOM - FOSphenytoin in non-traumatic COMa
Study objectives	Seizures in acute encephalopathies are associated with neuro-cognitive impairment following recovery. Prevention of the seizures (which may manifest as convulsions, abnormal motor posturing or electrographic seizures) during the acute illness may improve the neuro-cognitive outcome.
Ethics approval(s)	Not provided at time of registration
Health condition(s) or problem(s) studied	Acute non-traumatic encephalopathies
Intervention	This is a double blind randomised controlled trial to evaluate the safety and efficacy of a single intramuscular (im) injection of Fosphenytoin, 20 mg Phenytoin equivalents/kg in children with acute non-traumatic encephalopathies, given at admission to prevent seizures and abnormal motor posturing during stay in hospital and neuro-cognitive deficits assessed at three and 24 months. The control intervention is a placebo of normal saline.
Intervention type	Drug
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	Fosphenytoin
Primary outcome measure(s)	1. The proportion of patients with clinical or electrographic seizures after intervention 2. The proportion of patients with abnormal motor posturing after intervention 3. The proportion of patients with neuro-cognitive deficits three months after discharge
Key secondary outcome measure(s)	1. Mortality in either group 2. Proportion of children who develop status epilepticus after intervention 3. Frequency and types of adverse events 4. Mean duration of seizures that occur after the intervention 5. Changes in cerebral blood flow velocity in the middle cerebral artery during seizure episodes 6. Time to regain full consciousness 7. Duration of hospitalisation 8. Neurocognitive deficits at 24 months The sample of 500 (i.e. 250 in each arm) has a 90% power at 5% level of significance to detect the following changes after allowing for a 20% loss to follow up and death: a. A 50% reduction (from 27 to 13.5%) in patients with at least one seizure lasting more than five minutes or more than three seizures of any duration b. A 50% reduction (from 34 to 17%) in patients who will develop abnormal motor posturing c. A 50% reduction in cognitive impairment from 24 to 12% as measured by Evoked Response Potentials (ERP). An interim analysis is planned after 200 children have been recruited into the trial.
Completion date	31/12/2009

Eligibility

Participant type(s)	Patient
Age group	Child
Lower age limit	9 Months
Upper age limit	13 Years
Sex	All
Target sample size at registration	500
Key inclusion criteria	1. Children who are unable to localise a painful stimulus 30 minutes after a seizure or correction of hypoglycaemia 2. Written informed consent from the parents or guardian 3. Age 9 months to 13 years
Key exclusion criteria	1. Children with a history of epilepsy, significant developmental delay, cerebral palsy, or sickle cell disease 2. Children who would have received phenytoin for treatment of seizures before recruitment 3. Evidence of head trauma
Date of first enrolment	28/12/2004
Date of final enrolment	31/12/2007

Locations

Countries of recruitment

United Kingdom
England
Kenya

Study participating centre

University College London

London
WC1N 2AP
United Kingdom

Results and Publications

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