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NCT Number: NCT01982812

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

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.

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Key information

Conditions

Seizure Brain Diseases Central Nervous System Diseases Central Nervous System Infections Central Nervous System Parasitic Infections Central Nervous System Protozoal Infections Cerebral Malaria Epilepsy Infections Malaria Malaria, Cerebral Mosquito-Borne Diseases Nervous System Diseases Neurologic Manifestations Parasitic Diseases Pathological Conditions, Signs and Symptoms Protozoan Infections Seizures Signs and Symptoms Vector Borne Diseases

Age range

24 month–83 month

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Queen Elizabeth Central Hospital

Blantyre, 3, Malawi

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Oral Levetiracetam

Drug

liquid, 40 mg/kg loading dose and 30mg/kg every 12 hours via nasogastric tube for 3 days

Other names: Keppra

Standard AED

Drug

Active comparitor, Standard AED

Other names: Standard regimen of AED therapy

Primary outcomes

  1. Minutes With Seizure on EEG

    Time frame: 72 hours

    Comparing LVT to standard AED the number of minutes spent in seizure per cEEG in the 72 hours after treatment allocation.

Secondary outcomes

  1. Required Additional AED

    Time frame: 7 days

    Additional AEDs required (including for breakthrough seizures in LVT group) during admission for seizure control (yes/no)

  2. Mean Time From Admission to BCS >/= 4

    Time frame: 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

  3. Sequelae

    Time frame: 7 days

    Neurologic outcome in 3 categories--

    • Neurologically intact at discharge
    • Neurologic sequelae at discharge--specifically new sensory or motor deficits, ongoing seizures, or behavioral abnormalities based upon a physician examination at discharge
    • Died during admission, never discharged

Sponsors and collaborators

Lead sponsor

University of Rochester

Other

Collaborators

  • National Institute of Neurological Disorders and Stroke (NINDS)

Registry information

Official study title

A Safety and Feasibility Study of Enteral Levetiracetam vs. Phenobarbital for Seizure Control in Pediatric Cerebral Malaria

Acronym: LVT2

Important dates

Study start
2014
Primary completion
2015
Study completion
2015
First posted
Nov 13, 2013
Registry last updated
Jul 29, 2016

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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