Prevention of Epileptic Seizures in Acute intraCerebral Haemorrhage

NCT ID: NCT02631759

Last Updated: 2025-09-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-10-31
• Study Completion Date: 2021-06-07

Brief Summary

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.

Conditions

Acute intraCerebral Haemorrhage

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Lévétiracetam

52 patients will be recruited over 2 years in the experimental group

Group Type: EXPERIMENTAL

Lévétiracetam

Intervention Type: DRUG

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).

Placebo

52 patients will be recruited over 2 years in the control group

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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).

Interventions

Lévétiracetam

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).

Intervention Type: DRUG

Placebo

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).

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hospices Civils de Lyon

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Laure Peter-Derex, MD

Role: STUDY_DIRECTOR

Hospices Civils de Lyon

Locations

Department of functional neurology and epileptology

Lyon, , France

Countries

France

References

Peter-Derex L, Philippeau F, Garnier P, Andre-Obadia N, Boulogne S, Catenoix H, Convers P, Mazzola L, Gouttard M, Esteban M, Fontaine J, Mechtouff L, Ong E, Cho TH, Nighoghossian N, Perreton N, Termoz A, Haesebaert J, Schott AM, Rabilloud M, Pivot C, Dhelens C, Filip A, Berthezene Y, Rheims S, Boutitie F, Derex L. Safety and efficacy of prophylactic levetiracetam for prevention of epileptic seizures in the acute phase of intracerebral haemorrhage (PEACH): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Neurol. 2022 Sep;21(9):781-791. doi: 10.1016/S1474-4422(22)00235-6.

Reference Type: RESULT

PMID: 35963261 (View on PubMed)

Other Identifiers

2014-845

Identifier Type: -

Identifier Source: org_study_id