From the Guidelines
The RAMPART trial remains a cornerstone in the management of status epilepticus, with its findings still valid and highly relevant in current clinical practice. The trial's comparison of intramuscular midazolam to intravenous lorazepam for the treatment of status epilepticus demonstrated that intramuscular midazolam is at least as effective as intravenous lorazepam for seizure cessation, as supported by the most recent clinical policy approved by the ACEP board of directors in 2024 1. This policy, published in the Annals of Emergency Medicine, highlights the importance of rapid and effective treatment of seizures in the emergency department setting.
Key Points
- The RAMPART trial's results have been reinforced by subsequent studies and guidelines, including the 2024 clinical policy which emphasizes the critical issues in the management of adult patients presenting to the emergency department with seizures 1.
- The simplicity and efficacy of intramuscular midazolam make it a valuable option in both pre-hospital and hospital settings, especially where time to treatment is critical and IV access may be challenging.
- The trial's findings continue to influence treatment protocols for status epilepticus, with a focus on rapid seizure control to prevent neurological damage.
- While the ESETT trial, referenced in the 2024 policy, compared levetiracetam, fosphenytoin, and valproate for the treatment of status epilepticus, the RAMPART trial's specific comparison of intramuscular midazolam to intravenous lorazepam remains uniquely relevant to the initial management of seizures in emergency situations 1.
Clinical Implications
The validity and relevance of the RAMPART trial are underscored by its impact on clinical practice, particularly in the emergency department and pre-hospital settings. The trial's demonstration of the efficacy of intramuscular midazolam supports its continued use as a first-line treatment for status epilepticus, given its ease of administration and comparable efficacy to intravenous lorazepam. This approach aligns with the goal of minimizing morbidity, mortality, and improving quality of life for patients presenting with seizures, as emphasized in the 2024 clinical policy 1.
From the Research
RAMPART Trial Validity
- The RAMPART trial, which stands for Rapid Anticonvulsant Medication Prior to Arrival Trial, was a double-blind randomized clinical trial conducted in 2011 to determine the efficacy of intramuscular midazolam versus intravenous lorazepam in the prehospital treatment of status epilepticus by paramedics 2.
- As of 2023, lessons learned from the RAMPART and ESETT randomized controlled trials have been considered, and suggestions have been made for how to best conduct future trials investigating status epilepticus 3.
- In 2024, the design of the ongoing RAMPART trial was adapted in response to external evidence, providing an example for trials that take many years to run and report 4.
- However, it is essential to note that the RAMPART trial mentioned in the 2024 study 4 appears to be a different trial, as it investigates immune checkpoint inhibitor therapy in the adjuvant renal cancer setting, whereas the original RAMPART trial focused on status epilepticus.
- The validity of the original RAMPART trial is not directly addressed in the provided studies from 2024 and 2025, which discuss different topics, such as antihypertensive medication timing and rilzabrutinib in antihistamine-refractory chronic spontaneous urticaria 5, 6.
- Therefore, based on the available information, it can be inferred that the original RAMPART trial is still a relevant study in the field of status epilepticus treatment, but its validity and relevance may have been impacted by subsequent studies and changes in medical practices 2, 3.