Clinical Trial: Enteral Levetiracetam For Seizure Control In Pediatric Cerebral Malaria

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Dose-Escalation, Safety And Feasibility Study Of Enteral Levetiracetam For Seizure Control In Pediatric Cerebral Malaria

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, dose- escalation, 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 Summary: 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 propose to conduct a dose- escalation, 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 will be escalated based upon efficacy and toxicity endpoints with efficacy defined as seizure freedom in 75% of children during the 24 hours post LVT administration. Generally, only ~20% of children admitted with CM and seizures who receive standard AED treatment remain seizure free during the first 24 hours after admission. Safety assessments will include monitoring for problems related to NGT placement and medication delivery, laboratory parameters at 24 hours and 7 days post LVT, and overall case fatality rates. If efficacy endpoints are not met but enteral LVT is otherwise tolerated, LVT doses of ~3 times the standard dose used for other seizure-related conditions will be assessed. Pharmacok
Sponsor: University of Rochester

Current Primary Outcome: Freedom From Seizure [ Time Frame: 24 hours ]

Number of subjects free of seizure at 24 hours after initiation of treatment


Original Primary Outcome: Freedom From Seizure [ Time Frame: 24 hours ]

freedom from seizure of 75% of subjects for 24 hours after initiation of treatment


Current Secondary Outcome:

  • Toxicity Related to LVT [ Time Frame: 1 week ]
    Toxicity including vomiting, aspiration, complications related to the NGT, laboratory parameters at 24 hours and 1 week post LVT administration, and an overall acute case fatality rate significantly above the consistent historical ward average for CM. Pk studies to evaluate LVT absorption and elimination in pediatric CM.
  • Range of Plasma Concentration of LVT Across All Individuals [ Time Frame: 72 hours ]
    Range of plasma LVT concentrations will be determined through HPLC method at eight timepoints post administration to evaluate LVT absorption and elimination in pediatric CM.


Original Secondary Outcome:

  • Toxicity [ Time Frame: 1 week ]
    Toxicity including vomiting, aspiration, complications related to the NGT, laboratory parameters at 24 hours and 1 week post LVT administration, and an overall acute case fatality rate significantly above the consistent historical ward average for CM. Pk studies to evaluate LVT absorption and elimination in pediatric CM.
  • Plasma concentration of LVT [ Time Frame: 72 hours ]
    Plasma LVT concentrations will be determined through HPLC method at eight timepoints post administration to evaluate LVT absorption and elimination in pediatric CM.


Information By: University of Rochester

Dates:
Date Received: July 19, 2012
Date Started: January 2013
Date Completion:
Last Updated: August 3, 2016
Last Verified: August 2016