None listed
Conditions
Brief summary
The aim of this study is to examine the effectiveness of perampanel in the prevention of post-stroke seizures. Patients will be randomised to receive perampanel or placebo for 16 weeks. Doses will be escalated over the first four weeks before patients enter an assessment phase for the remainder of the trial. Patients will be followed up for 52 weeks. The primary outcome is the proportion of patients seizure free at the conclusion of the 52 week period. Secondary endpoints include measures of drug safety, tolerability and quality of life. In a subset of participants glutamate concentrations in the brain will be measured by MRI to assess whether they can be used to predict development of post-stroke seizures. This will be the third randomised trial examining the prevention of seizures after stroke. A positive study would support a larger randomised phase III trial of perampanel for prevention of post-stroke seizures. The novel use of 7T MRI to quantify glutamate offers the opportunity to assess if a non-invasive biomarker can help stratify seizure risk so that at-risk patients can be targeted for preventative treatment.
Interventions
The interventional treatment to be used in this trial is the oral anti-epileptic drug, perampanel. Perampanel is an AMPA-receptor antagonist. A comparator (placebo) medication indistinguishable from the active drug will also be used.
Patients with acute cortical ischaemic or haemorrhagic stroke will be recruited within 7 days of stroke onset. A subset will undergo a 7T MRI scan. Patients will be randomised to receive perampanel or placebo for 16 weeks and be observed for a further 36 weeks, un
The interventional treatment to be used in this trial is the oral anti-epileptic drug, perampanel. Perampanel is an AMPA-receptor antagonist. A comparator (placebo) medication indistinguishable from the active drug will also be used. Patients with acute cortical ischaemic or haemorrhagic stroke will be recruited within 7 days of stroke onset. A subset will undergo a 7T MRI scan. Patients will be randomised to receive perampanel or placebo for 16 weeks and be observed for a further 36 weeks, until the study ends at 52 weeks. For patients randomised to the active arm, perampanel will be started at 2mg at night and increased after 2 weeks to 4mg at night. At the start of the assessment phase (week 5-16), perampanel will be increased to 6mg. Participants will remain on 6mg from week 5 until the end of week 16 unless seizures or side effects occur. At the end of the assessment phase all medications will be ceased and patients will enter the observation phase (week 17-52). Participants will have 6 visits after randomisation over the 52-week study period, during which post-stroke seizures, compliance and side effects will be assessed by investigators. In escalation and assessment phases, participants will be questioned regarding their medication adherence, and tablet/bottle counting will be performed to aid in compliance assessment. Visits will occur at 2, 4, 8 and 16 weeks, and again at 6 and 12 months. If a post-stroke seizure occurs during the escalation phase, then after assessment by a study neurologist, standard titration will continue to occur if clinically appropriate. If multiple seizures occur during this period, additional anti-epileptic drugs may be prescribed at the discretion of the treating neurologist. If seizures occur during the assessment or observation phase, then the endpoint will be reached and the blind broken. The patient will be withdrawn from the study at this point and managed as per their treating physician. If side effects develop and are intolerable, one dose reduction of 2mg can occur.
Sponsors
Alfred Health
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Prevention
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Radiological (CT, CT perfusion or MRI) evidence of acute cortical ischaemic stroke or lobar haemorrhage within 7 days of symptom onset If enrolment is feasible prior to obtaining MRI (or MRI is contraindicated), cortical involvement can be inferred by either (1) evidence of large vessel (ICA, M1/M2) occlusion on CT angiography at admission or (2) clinical evidence of a cortical syndrome such as aphasia, neglect/inattention or visual field defect 2. No previous anti-epileptic drug use 3. Able to give informed consent or proxy consent 4. Pre-admission mRS<4
Exclusion criteria
1. Preadmission Modified Rankin Scale (mRS) > 3 2. Acute stroke more than 7 days from onset 3. Previous ischaemic or haemorrhagic stroke within preceding 12 months 4. Significant risk factors for non stroke-related epilepsy 5. Previously diagnosed epilepsy (excluding benign childhood epilepsies) 6. Additional epileptogenic intra-cranial pathology 7. Previous intracranial surgery 8. History of major psychiatric morbidity (such as psychiatric illness requiring hospitalisation or history of psychosis, major depression or suicidality) within the last 2 years 9. Pregnant or breast-feeding 10. Excessive alcohol or recreational drug use 11. Unable to obtain informed consent from patient or substitute decision maker
Outcome results
None listed