The RAMER Reviews: The PEACH Trial
By: Suji Cha, DO
Edited by: Timothy Khowong, MD, MSEd
Background
Seizures can occur as a complication in patients with acute, spontaneous intracerebral hemorrhage. Prior studies have shown that early seizures in patients with intracerebral hemorrhage can be associated with a worse functional outcome and increased risk of death. Levetiracetam is commonly ordered in the emergency department for seizure prophylaxis in these patients.
The Study
The PEACH trial was a randomized, double-blinded, and placebo-controlled study performed across three stroke centers in France. The objective of the trial was to assess if the prophylactic use of Levetiracetam reduced the occurrence of seizures in patients with spontaneous intracerebral hemorrhage. The outcome that was measured was the occurrence of a clinical seizure or a seizure recorded on EEG within 72 hours of inclusion in the study.
A total of 50 patients were enrolled and of them, 24 were assigned to the Levetiracetam group and 26 were assigned to the placebo group. There was a large and statistically significant difference between the groups in that there were clinical or electrographic seizures in 16% of the Levetiracetam group and 43% of the placebo group within 72 hours of inclusion into the trial.
There were several limitations to this trial including a small sample size collected over the period of three years, which leads the reader to think that the generalizability of the study is limited, as evidenced by the large differences in the baseline characteristics between the two groups. The study prematurely ended secondary to limited fundings as a result of the COVID-19 pandemic. The dosing of the Levetiracetam was not adjusted appropriately based on weight, and was provided at a standardized dose for all of the patients in that group. Concurrent video monitoring was not available with the cEEG, and therefore subtle clinical seizures may have been missed.
Discussion:
It remains unclear whether seizure prophylaxis in acute spontaneous intracerebral hemorrhage leads to improved functional outcomes. The current 2022 American Heart Association/American Stroke Association guideline recommends against the use of prophylactic seizure medications in patients with spontaneous ICH, because prior studies have shown no added benefit of improving functional outcome, long-term seizure control, or mortality. The conclusion that the authors published is likely true: further studies with a larger sample size will need to be performed in order to guide future clinical decisions.
References:
1. Peter-Derex, Laure et al. “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.” The Lancet. Neurology vol. 21,9 (2022): 781-791. doi:10.1016/S1474-4422(22)00235-6
2. Greenberg, Steven M et al. “2022 Guideline for the Management of Patients With Spontaneous Intracerebral Hemorrhage: A Guideline From the American Heart Association/American Stroke Association.” Stroke vol. 53,7 (2022): e282-e361. doi:10.1161/STR.0000000000000407
3. Fang, Taolin et al. “Levetiracetam for Seizure Prophylaxis in Neurocritical Care: A Systematic Review and Meta-analysis.” Neurocritical care vol. 36,1 (2022): 248-258. doi:10.1007/s12028-021-01296-z
4. Law, Zhe Kang et al. “Incidence and predictors of early seizures in intracerebral haemorrhage and the effect of tranexamic acid.” European stroke journal vol. 5,2 (2020): 123-129. doi:10.1177/2396987320901391