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

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ClinicalTrials.gov Identifier: NCT01982812
Recruitment Status : Completed
First Posted : November 13, 2013
Results First Posted : July 29, 2016
Last Update Posted : July 29, 2016
Sponsor:
Collaborator:
National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by (Responsible Party):
Gretchen Birbeck, University of Rochester

Study Description
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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.

Condition or disease Intervention/treatment Phase
Seizure Epilepsy Cerebral Malaria Drug: Oral Levetiracetam Drug: Standard AED Phase 2

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.
Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 44 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Safety and Feasibility Study of Enteral Levetiracetam vs. Phenobarbital for Seizure Control in Pediatric Cerebral Malaria
Study Start Date : January 2014
Actual Primary Completion Date : June 2015
Actual Study Completion Date : June 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Malaria Seizures

Arms and Interventions
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Arm Intervention/treatment
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


Outcome Measures
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Primary Outcome Measures :
  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 Outcome Measures :
  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--

    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


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   24 Months to 83 Months   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01982812


Locations
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Malawi
Queen Elizabeth Central Hospital
Blantyre, Malawi, 3
Sponsors and Collaborators
University of Rochester
National Institute of Neurological Disorders and Stroke (NINDS)
Investigators
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Principal Investigator: Gretchen L Birbeck, M.D. University of Rochester
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Gretchen Birbeck, Professor, University of Rochester
ClinicalTrials.gov Identifier: NCT01982812    
Other Study ID Numbers: 7R01NS074409-02 ( U.S. NIH Grant/Contract )
R01NS074409 ( U.S. NIH Grant/Contract )
First Posted: November 13, 2013    Key Record Dates
Results First Posted: July 29, 2016
Last Update Posted: July 29, 2016
Last Verified: June 2016
Individual Participant Data (IPD) Sharing Statement:
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:
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Malaria
Malaria, Cerebral
Seizures
Central Nervous System Diseases
Nervous System Diseases
Protozoan Infections
Parasitic Diseases
 Neurologic Manifestations
Central Nervous System Protozoal Infections
Central Nervous System Parasitic Infections
Central Nervous System Infections
Levetiracetam
Anticonvulsants
Nootropic Agents