Clinical trial NCT01982812: A Safety and Feasibility Study of Enteral LVT vs. Standard of Care for Seizure Control in Pediatric CM
Official title: A Safety and Feasibility Study of Enteral Levetiracetam vs. Phenobarbital for Seizure Control in Pediatric Cerebral Malaria
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Seizure
Epilepsy
Cerebral Malaria
Lead sponsor: University of Rochester
Sponsor class: OTHER
Collaborators: name: National Institute of Neurological Disorders and Stroke (NINDS)
First posted: 2013-11-13
Enrollment: 44
Sex: ALL
Minimum age (years): 24
Maximum age (years): 83
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Pediatric cerebral malaria (CM) affects more than 3 million children each year killing \~20% and leaving one third of survivors with long term neurologic and psychiatric sequelae. Seizures occur commonly with CM and are associated with an increased risk of death and neuropsychiatric disabilities. In this Malawi-based, safety and feasibility study of enteral levetiracetam in pediatric CM, the investigators will lay the groundwork for future efficacy studies aimed at improving seizure control and ultimately decreasing the neurologic morbidity of pediatric CM.

Detailed description: Cerebral malaria (CM) affects \~3 million children each year, primarily in sub-Saharan Africa. Antimalarial medications can rapidly clear P. falciparum parasites, but mortality rates remain high (12-25%). Survivors do not escape unscathed--\~30% experience neurologic sequelae including epilepsy, behavioral disorders and gross neurologic deficits. Acute seizures occur commonly in CM and are associated with higher neurologic morbidity and mortality. Seizure management in malaria endemic regions is challenging because the available antiepileptic drugs (AED) induce respiratory suppression and assisted ventilation is unavailable. More optimal seizure control may improve neurologic outcomes in pediatric CM survivors, especially if the medication used is affordable and can be delivered safely and easily in resource limited settings. The investigators conducted a dose- escalation study detailed elsewhere (NCT01660672) to determine the optimal dose for use in this safety and feasibility study of enteral levetiracetam (LVT) for seizure control in children with CM and seizures admitted to Queen Elizabeth Central Hospital in Blantyre, Malawi. Enteral LVT given via nasogastric tube (NGT) rather than an intravenous (IV) formulation will be used since LVT has excellent enteral bioavailability and IV formations are not affordable in most malaria-endemic regions. LVT 40mg/kg followed by 30mg per kg Q12 hourly. Children admitted with cerebral malaria and seizures will be randomized to LVT vs. standard of care with phenobarbital as needed comparing seizure control, safety, and neurological outcomes.

Eligibility criteria: Inclusion Criteria:

* Comatose with Blantyre Comas Score ≤ 2
* P. falciparum parasitemia via thick blood film or rapid diagnostic test
* Active seizure in past 24 hours

Exclusion Criteria:

* Serum creatinine \> 2mg/dL
* Pre-admission/concomitant treatment with antiretroviral medications for HIV (ARVs), antituberculous treatments(ATTs), or chronic use of any other enzyme-inducing medications

Primary outcomes:
measure: Minutes With Seizure on EEG
timeFrame: 72 hours
Secondary outcomes:
measure: Required Additional AED
timeFrame: 7 days
measure: Mean Time From Admission to BCS >/= 4
timeFrame: 7 days
measure: Sequelae
timeFrame: 7 days
Other outcomes:
Locations:
city: Blantyre
country: Malawi
facility: Queen Elizabeth Central Hospital
Study officials:
affiliation: University of Rochester
name: Gretchen L Birbeck, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Birbeck GL, Herman ST, Capparelli EV, Dzinjalamala FK, Abdel Baki SG, Mallewa M, Toto NM, Postels DG, Gardiner JC, Taylor TE, Seydel KB. A clinical trial of enteral Levetiracetam for acute seizures in pediatric cerebral malaria. BMC Pediatr. 2019 Nov 1;19(1):399. doi: 10.1186/s12887-019-1766-2.