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A Safety and Feasibility Study of Enteral LVT vs. Standard of Care for Seizure Control in Pediatric CM (LVT2)

This study has been completed.
National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by (Responsible Party):
Gretchen Birbeck, University of Rochester Identifier:
First received: November 5, 2013
Last updated: June 20, 2016
Last verified: June 2016
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.

Condition Intervention Phase
Cerebral Malaria
Drug: Oral Levetiracetam
Drug: Standard AED
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Safety and Feasibility Study of Enteral Levetiracetam vs. Phenobarbital for Seizure Control in Pediatric Cerebral Malaria

Resource links provided by NLM:

Further study details as provided by University of Rochester:

Primary Outcome Measures:
  • Minutes With Seizure on EEG [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
    Comparing LVT to standard AED the number of minutes spent in seizure per cEEG in the 72 hours after treatment allocation.

Secondary Outcome Measures:
  • Required Additional AED [ Time Frame: 7 days ] [ Designated as safety issue: No ]
    Additional AEDs required (including for breakthrough seizures in LVT group) during admission for seizure control (yes/no)

  • Mean Time From Admission to BCS >/= 4 [ Time Frame: 7 days ] [ Designated as safety issue: No ]

    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 [ Time Frame: 7 days ] [ Designated as safety issue: No ]

    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

Enrollment: 44
Study Start Date: January 2014
Study Completion Date: June 2015
Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Oral Levetiracetam
Oral Levetiracetam administered by NG tube.
Drug: Oral Levetiracetam
liquid, 40 mg/kg loading dose and 30mg/kg every 12 hours via nasogastric tube for 3 days
Other Name: Keppra
Active Comparator: Standard AED
Standard AED regimen
Drug: Standard AED
Active comparitor, Standard AED
Other Name: Standard regimen of AED therapy

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.

Ages Eligible for Study:   24 Months to 83 Months   (Child)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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
  Contacts and Locations
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Please refer to this study by its identifier: NCT01982812

Queen Elizabeth Central Hospital
Blantyre, Malawi, 3
Sponsors and Collaborators
University of Rochester
National Institute of Neurological Disorders and Stroke (NINDS)
Principal Investigator: Gretchen L Birbeck, M.D. University of Rochester
  More Information

Responsible Party: Gretchen Birbeck, Professor, University of Rochester Identifier: NCT01982812     History of Changes
Other Study ID Numbers: 7R01NS074409-02  R01NS074409 
Study First Received: November 5, 2013
Results First Received: April 28, 2016
Last Updated: June 20, 2016
Health Authority: Study Monitoring Committee Malawi:
Malawi's Pharmacy Medicines and Poisons Board (PMPB)Malawi:
Individual Participant Data  
Plan to Share IPD: Yes
Plan Description: After the finding have been published, the de-identified study data will be available to other researchers on request pending a review of their plans for using the data.

Additional relevant MeSH terms:
Malaria, Cerebral
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Protozoan Infections
Parasitic Diseases
Neurologic Manifestations
Signs and Symptoms
Central Nervous System Protozoal Infections
Central Nervous System Parasitic Infections
Central Nervous System Infections
Nootropic Agents
Neuroprotective Agents
Protective Agents
Physiological Effects of Drugs processed this record on October 28, 2016