Prehospital Early Administration of Ketamine for Status Epilepticus in Epileptic Kids (PEAK-SEEK)

NCT ID: NCT07095842

Last Updated: 2025-08-05

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 668 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-08-03
• Study Completion Date: 2026-08-01

Brief Summary

The goal of this pragmatic, decentralized, pre-consented, event-driven, randomized controlled trial is to investigate the efficacy of add-on ketamine to second-dose midazolam for prehospital treatment of epileptic children with convulsive status epilepticus.

Detailed Description

Status epilepticus (SE) is the most prevalent neurological emergency in children. Benzodiazepines (BDZs) remain the first-line anti-seizure medication (ASM) for SE, but about one-third of seizures are not controlled by BDZs. Moreover, second-line ASMs (levetiracetam, valproate, phenytoin) fail to terminate BDZ-refractory SE in 50% of cases. Such prolonged SE is linked with progressive brain damage and an increased risk of epilepsy, irreversible neurodevelopmental sequelae, and mortality. Accordingly, early control of SE is critical for enhancing clinical outcomes.

A possible strategy for rapid control of SE is using early ASM combination. Ketamine seems a promising choice for such a combination. Ketamine acts to antagonize N-methyl-D-aspartate (NMDA) receptors, which become increasingly upregulated and trafficked to the synaptic membrane during ongoing seizure activity. Numerous observational studies have demonstrated that administration of ketamine is associated with termination or attenuation of refractory SE (RSE) and super-refractory SE (SRSE). Furthermore, the recently published Ket-Mid study showed that the ketamine-midazolam combination was more effective than midazolam alone in the initial treatment of pediatric generalized CSE. However, the Ket-Mid study also highlighted a significant delay in hospital arrival and administration of first-line ASM, by a median of 34 minutes, reflecting delayed access to emergency care due to socioeconomic challenges, geographic barriers, and limited prehospital emergency medical services. Such a challenge also applies to resource-limited settings, where treatment delays are more common. Notably, a review by Gaínza-Lein et al. of 15 studies involving 2212 patients with SE reported average times to ASM treatment and hospital arrival of 42.4 and 56 minutes, respectively. Such delay to the administration of ASM is associated with increased resistance to BZDs, longer SE, and increased risk of complications. Accordingly, there is a growing interest in the early use of ASM for prehospital treatment of SE.

Ketamine has been used in prehospital setting for a long time, mainly for sedation and analgesia purposes with a high safety profile. Multiple observational studies have reported the efficacy of ketamine in the pre-hospital emergency treatment of BZD-refractory status epilepticus. However, this was not adequately investigated in clinical trials.

The present study (Prehospital Early Administration of Ketamine for Status Epilepticus in Epileptic Kids, PEAK-SEEK) aims to investigate the efficacy of adding ketamine to second-dose midazolam vs. second-dose midazolam alone as ASM for prehospital treatment of epileptic children with convulsive status epilepticus.

Conditions

Convulsive Status EPILEPTICUS

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Ketamine + Midazolam

Group Type: EXPERIMENTAL

Ketamine

Intervention Type: DRUG

Intramuscular ketamine 2 mg/kg (max 90 mg)

Midazolam

Intervention Type: DRUG

Intramuscular midazolam 0.2 mg/kg (max 10 mg)

Midazolam

Group Type: ACTIVE_COMPARATOR

Midazolam

Intervention Type: DRUG

Intramuscular midazolam 0.2 mg/kg (max 10 mg)

Interventions

Ketamine

Intramuscular ketamine 2 mg/kg (max 90 mg)

Intervention Type: DRUG

Midazolam

Intramuscular midazolam 0.2 mg/kg (max 10 mg)

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Age from 2 to 16 years.
• Established diagnosis of epilepsy of at least 1 year duration.
• History of at least 1 episode of convulsive status epilepticus in the preceding 12 months.

Exclusion Criteria

• Failure to obtain informed consent.
• Known allergies or contraindications to ketamine.
• Known contraindications to intramuscular injection.
• Presence of another family member included in the same trial.
• Having subsequent events (only the index event will be included).

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 16 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sohag University

OTHER

Sponsor Role: lead

Responsible Party

Elsayed Abdelkreem

Assistant Professor of Pediatrics

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Department of Pediatrics at Sohag University Hospital

Sohag, , Egypt

Site Status: RECRUITING

Countries

Egypt

Central Contacts

Elsayed Abdelkreem

Role: CONTACT

d.elsayedmohammed@med.sohag.edu.eg

1114232126 ext. +20

Facility Contacts

Abdelrahim A Sadek, MD, PhD

Role: primary

abdoneurology@yahoo.com

Other Identifiers

Soh-Med-25-7-4PD

Identifier Type: -

Identifier Source: org_study_id