A Safety and Feasibility Study of Enteral LVT vs. Standard of Care for Seizure Control in Pediatric CM

Phase 2

Completed

• Conditions: Epilepsy; Seizure; Cerebral Malaria
• Interventions: Drug: Standard AED; Drug: Oral Levetiracetam

• Registration Number: NCT01982812
• Lead Sponsor: University of Rochester

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2013-11-05
• Study First Submitted QC: 2013-11-05
• Study First Posted: 2013-11-13
• Study Start: 2014-01
• Primary Completion: 2015-06
• Study Completion: 2015-06
• Results First Submitted: 2016-04-28
• Status Verified: 2016-06
• Results First Submitted QC: 2016-06-20
• Last Update Submitted: 2016-06-20
• Results First Posted: 2016-07-29
• Last Update Posted: 2016-07-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 44

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Standard AED	Standard AED	Standard AED regimen
Oral Levetiracetam	Oral Levetiracetam	Oral Levetiracetam administered by NG tube.

Primary Outcome Measures

Name	Time	Method
Minutes With Seizure on EEG	72 hours	Comparing LVT to standard AED the number of minutes spent in seizure per cEEG in the 72 hours after treatment allocation.

Secondary Outcome Measures

Name	Time	Method
Required Additional AED	7 days	Additional AEDs required (including for breakthrough seizures in LVT group) during admission for seizure control (yes/no)
Mean Time From Admission to BCS >/= 4	7 days	The mean time in hours from admission until the subject reaches Blantyre Coma Scale of greater than or equal to 4. Participants who died are excluded from this analysis.; The Blantyre Coma Score has ranges from 0-5 based upon the a sum of the following 3 domains- Eye movement; 1 - Watches or follows 0 - Fails to watch or follow; Best motor response 2 - Localizes painful stimulus 1 - Withdraws limb from painful stimulus 0 - No response or inappropriate response; Best verbal response 2 - Cries appropriately with pain, or, if verbal, speaks; 1 - Moan or abnormal cry with pain 0 - No vocal response to pain
Sequelae	7 days	Neurologic outcome in 3 categories--; 1. Neurologically intact at discharge; 2. Neurologic sequelae at discharge--specifically new sensory or motor deficits, ongoing seizures, or behavioral abnormalities based upon a physician examination at discharge; 3. Died during admission, never discharged

Trial Locations

Locations (1)

Queen Elizabeth Central Hospital; 🇲🇼 Blantyre, Malawi