PEACH: Prevention of Epileptic Seizures in Acute intraCerebral Haemorrhage

Sponsor

Hospices Civils de Lyon (Other)

Overall Status

Completed

CT.gov ID

NCT02631759

Collaborator

(none)

Enrollment

Location

Arms

56.2

Actual Duration (Months)

0.9

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Acute intraCerebral Haemorrhage	Drug: Lévétiracetam Drug: Placebo	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

50 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Prevention of Epileptic Seizures in Acute intraCerebral Haemorrhage

Actual Study Start Date :

Oct 1, 2016

Actual Primary Completion Date :

Apr 9, 2021

Actual Study Completion Date :

Jun 7, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Lévétiracetam 52 patients will be recruited over 2 years in the experimental group	Drug: 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).
Placebo Comparator: Placebo 52 patients will be recruited over 2 years in the control group	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).

Arm

Intervention/Treatment

Experimental: Lévétiracetam

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

Drug: 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).

Placebo Comparator: Placebo

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

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).

Outcome Measures

Primary Outcome Measures

Occurrence of at least one clinical or electrical epileptic seizure recorded on continuous 48 hours holter EEG [48 hours]

Secondary Outcome Measures

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]

Other Outcome Measures

Occurrence of early (day-0 to day-30 ) and late (from day-30 to 12 months) clinical seizures [12 months]
Functional prognosis at 3 , 6 and 12 months evaluated by the modified Rankin scale [12 months]
Cerebral oedema and mass effect evaluated by comparing the admission brain CT scan with the control CT scan performed at 72 hours [72 hours]
Neurological status as assessed by the National Institute of Health Stroke Scale at 72 hours , 1 month and 3 months [3 months]
Quality of life measured by the Stroke impact Scale at 3, 6 and 12 months [12 months]
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) [3 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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