Trial Outcomes & Findings for Enteral Levetiracetam For Seizure Control In Pediatric Cerebral Malaria (NCT NCT01660672)

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

7 participants

Primary outcome timeframe

24 hours

Results posted on

2016-09-15

Participant Flow

Participant milestones

Participant milestones
Measure	LEVETIRACETAM Open label, dose escalation to optimal dose. LEVETIRACETAM: liquid, 40 mg/kg loading dose and 30mg/kg every 12 hours via nasogastric tube for 3 days--this is standard dose. If primary outcome is not reached, dose escalation to 150, 225, and 300% standard, as needed, will be conducted.
Overall Study STARTED	7
Overall Study COMPLETED	7
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Enteral Levetiracetam For Seizure Control In Pediatric Cerebral Malaria

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	LEVETIRACETAM n=7 Participants Open label, dose escalation to optimal dose. LEVETIRACETAM: liquid, 40 mg/kg loading dose and 30mg/kg every 12 hours via nasogastric tube for 3 days--this is standard dose. If primary outcome is not reached, dose escalation to 150, 225, and 300% standard, as needed, will be conducted.
Age, Continuous	40.8 months n=5 Participants
Age, Categorical <=18 years	7 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants
Region of Enrollment Malawi	7 participants n=5 Participants

PRIMARY outcome

Timeframe: 24 hours

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

Outcome measures

Outcome measures
Measure	LEVETIRACETAM n=7 Participants Open label, dose escalation to optimal dose. LEVETIRACETAM: liquid, 40 mg/kg loading dose and 30mg/kg every 12 hours via nasogastric tube for 3 days--this is standard dose.
Freedom From Seizure	7 individuals

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	LEVETIRACETAM n=7 Participants Open label, dose escalation to optimal dose. LEVETIRACETAM: liquid, 40 mg/kg loading dose and 30mg/kg every 12 hours via nasogastric tube for 3 days--this is standard dose.
Toxicity Related to LVT	0 participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	LEVETIRACETAM n=7 Participants Open label, dose escalation to optimal dose. LEVETIRACETAM: liquid, 40 mg/kg loading dose and 30mg/kg every 12 hours via nasogastric tube for 3 days--this is standard dose.
Range of Plasma Concentration of LVT Across All Individuals	35 mcg/ml Interval 20.0 to 50.0

OTHER_PRE_SPECIFIED outcome

Timeframe: day 7

Number of participants with neurologic sequelae at discharge

Outcome measures

Outcome measures
Measure	LEVETIRACETAM n=7 Participants Open label, dose escalation to optimal dose. LEVETIRACETAM: liquid, 40 mg/kg loading dose and 30mg/kg every 12 hours via nasogastric tube for 3 days--this is standard dose.
Number of Participants With Neurologic Sequelae at Discharge	2 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Upon admission

Retinopathy status may impact LVT efficacy and subject status will be analyzed based on this characteristic.

Outcome measures

Outcome measures
Measure	LEVETIRACETAM n=7 Participants Open label, dose escalation to optimal dose. LEVETIRACETAM: liquid, 40 mg/kg loading dose and 30mg/kg every 12 hours via nasogastric tube for 3 days--this is standard dose.
Number of Subjects With Retinopathy at Enrollment	4 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 0 hour

Pre-enrollment exposure to phenobarbitone may impact LVT efficacy, and analysis base on this characteristic will be evaluated.

Outcome measures

Outcome measures
Measure	LEVETIRACETAM n=7 Participants Open label, dose escalation to optimal dose. LEVETIRACETAM: liquid, 40 mg/kg loading dose and 30mg/kg every 12 hours via nasogastric tube for 3 days--this is standard dose.
Number of Subjects Exposed to Phenobarbitone Prior to Enrollment	3 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 7 days

Number of participants who required AEDS during admission(including for breakthrough seizures in the LVT group) during admission.

Outcome measures

Outcome measures
Measure	LEVETIRACETAM n=7 Participants Open label, dose escalation to optimal dose. LEVETIRACETAM: liquid, 40 mg/kg loading dose and 30mg/kg every 12 hours via nasogastric tube for 3 days--this is standard dose.
Number of Participants Requiring AED During Admission	6 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 7 days

Mean time from admission to a BCS score greater than or equal to 4. The BCS (Blantyre Coma Scale) is a 0-5 scale measuring motor response, verbal response and eye movement assessing the severity of coma in children with cerebral malaria. Lower scores correspond to more profound coma.

Outcome measures

Outcome measures
Measure	LEVETIRACETAM n=7 Participants Open label, dose escalation to optimal dose. LEVETIRACETAM: liquid, 40 mg/kg loading dose and 30mg/kg every 12 hours via nasogastric tube for 3 days--this is standard dose.
Mean Time to Return to a BCS Score Greater Than or Equal to 4	35.3 hours Interval 7.0 to 78.0

Adverse Events

LEVETIRACETAM

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	LEVETIRACETAM n=7 participants at risk Open label, dose escalation to optimal dose. LEVETIRACETAM: liquid, 40 mg/kg loading dose and 30mg/kg every 12 hours via nasogastric tube for 3 days--this is standard dose. This dose was effective in 7/7 children.
Blood and lymphatic system disorders Electrolyte	28.6% 2/7 • Number of events 3
Gastrointestinal disorders GI Symptoms	85.7% 6/7 • Number of events 6
Blood and lymphatic system disorders Hematologic abnormality	14.3% 1/7 • Number of events 1

Additional Information

Gretchen Birbeck

University of Rochester Medical Center

Phone: 585-273-4265

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place