Prevention of Epileptic Seizures in Acute intraCerebral Haemorrhage

Study Overview
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Brief Summary
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Haemorrhagic strokes represent about 10-15 % of all strokes and 30,000 cases per year in France. The 30-day death rate ranges from 30 to 55% (50% of deaths occurring within 48 hours). Currently, no urgent medical or surgical treatment has been shown to improve functional or vital prognosis. Clinical epileptic seizures frequency in acute intracerebral haemorrhage has been estimated between 4% and 16% but the occurrence of subclinical epileptic seizures (detected on the electroencephalogram (EEG) only) could be much more frequent (28 % to 40 %). Some studies have suggested that early repeated epileptic seizures may be associated with a worse neurological prognosis. Repeated epileptic seizures occurring in the acute phase may increase brain oedema, worsen, hypoxia and may lead to cellular death in the injured brain tissue. Thus, prevention of early epileptic seizures may improve neurological outcome. However, the efficacy of a systematic prophylactic antiepileptic treatment on clinical and subclinical epileptic seizures has not been evaluated in the setting of intracerebral haemorrhage. The current European guidelines recommend the use of antiepileptic drugs only when epileptic seizures occur. Primary objective: PEACH is a randomized controlled trial aiming at evaluating the impact of systematic prophylactic antiepileptic treatment with levetiracetam versus placebo in acute supratentorial spontaneous intracerebral haemorrhage. The primary endpoint is the occurrence of at least one clinical or electrical epileptic seizure recorded on continuous 48h holter EEG. Secondary Objectives:This study also aims to assess: Ä The efficacy of prophylactic treatment with levetiracetam on the number of EEG seizures, on the total duration of epileptic seizures continuously recorded on EEG, on the occurrence of some paroxysmal EEG patterns, on the number of clinical seizures occurred during 72 hours of diagnosis, on the occurrence of early (day-0 to day-30 ) and late (from day-30 to 12 months) clinical seizures, on the functional prognosis at 3 , 6 and 12 months evaluated by the modified Rankin scale , on the cerebral oedema and mass effect evaluated by comparing the admission brain CT scan with the control CT scan performed at 72 hours, on the neurological status as assessed by the National Institute of Health Stroke Scale at 72 hours , 1 month and 3 months and on the quality of life measured by the Stroke impact Scale at 3, 6 and 12 months. Ä The frequency of side effects related to treatment with levetiracetam (anxiety and depression assessed by the Hospital Anxiety and Depression Scale at 1 and 3 months) Sample Size: 104 patients will be recruited over 2 years.

Official Title
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Prevention of Epileptic Seizures in Acute intraCerebral Haemorrhage

Conditions
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Acute intraCerebral Haemorrhage

Intervention / Treatment
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* Drug: Lévétiracetam
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age greater than 18 years with no upper age limit Competent adult patient. Patient affiliated to the French National Health Insurance. Patient with supratentorial spontaneous intracerebral hemorrhage diagnosed by CT or MRI Early neurological symptoms less than 24 hours NIHSS score on admission between 5 and 25 Informed consent given by the patient or his legal representative Exclusion Criteria: Inaugural Seizures ( at the onset of symptoms associated with intracerebral hemorrhage ) Seizures occurring between the inclusion of the patient and the start of the EEG Other Intracerebral hemorrhage infratentorial , post-traumatic , related to a vascular malformation or an underlying tumor and secondarily hemorrhagic cerebral infarction Current antiepileptic treatment when intracerebral hemorrhage , or a history of epilepsy Modified Rankin Scale before intracerebral hemorrhage > 1 (indicating a preexisting disability) Serious illness which can affect the prognosis within 3 months Severe renal impairment ( creatinine clearance <30 ml / min) Pregnancy, lactation Known hypersensitivity to levetiracetam or other pyrrolidone derivatives , or any of the excipients. Untreated severe depression , psychotic disorders Lactose Intolerance Patient under measuring socio- legal protection

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lévétiracetam<br>52 patients will be recruited over 2 years in the experimental group | Drug: Lévétiracetam<br>* Levetiracetam will be administered at 500mg / 12h through IV started within 24 hours after enrollment in the study for at least 48 hours and for up to 5 days, then a per os administration will be made out as soon as oral will be possible, at a dose of 500mg / 12h (1g / day in two divided doses ) . The total duration of treatment will be 1 month and 15 days taking into account the processing taking decay phase. The decay phase takes place in two phases: A phase of 7 days of levetiracetam 250 mg every 12 hours ( morning and evening) Then a phase of 7 days of levetiracetam 250 mg every 24 hours (evening).<br>|
| Placebo Comparator: Placebo<br>52 patients will be recruited over 2 years in the control group | Drug: Placebo<br>* Placebo (NaCl 0,9%) will be administered at 500mg / 12h through IV started within 24 hours after enrollment in the study for at least 48 hours and for up to 5 days, then a per os administration will be made out as soon as oral will be possible, at a dose of 500mg / 12h (1g / day in two divided doses ) . The total duration of treatment will be 1 month and 15 days taking into account the processing taking decay phase. The decay phase takes place in two phases: A phase of 7 days of placebo 250 mg every 12 hours ( morning and evening) Then a phase of 7 days of placebo 250 mg every 24 hours (evening).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of at least one clinical or electrical epileptic seizure recorded on continuous 48 hours holter EEG |  | 48 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of electroencephalographic signs |  | 48 hours | 
| Number of EEG seizures |  | 48 hours | 
| Total duration of epileptic seizures continuously recorded on EEG |  | 48 hours | 
| occurrence of some paroxysmal EEG patterns |  | 48 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute intraCerebral Haemorrhage, Epileptic seizures, Lévétiracetam