SeizurePhase 2LVT2NCT01982812
A Safety and Feasibility Study of Enteral LVT vs. Standard of Care for Seizure Control in Pediatric CM
A Phase 2 study testing Oral Levetiracetam and Standard AED in people with Seizure and Epilepsy, run by University of Rochester at 1 site in Malawi.
Trial 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. Read more about this study
- Who is it for?
- Ages 24 to 83 months
- Conditions the study is for
- Seizure, Epilepsy, Cerebral Malaria
- What is being tested?
- Oral Levetiracetam and Standard AED
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 44 participants
- Where
- 1 siteMalawi
- Study dates
- Jan 2014to Jun 2015
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 24 to 83 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Comatose with Blantyre Comas Score ≤ 2
- P. falciparum parasitemia via thick blood film or rapid diagnostic test
- Active seizure in past 24 hours
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Safety and Feasibility Study of Enteral Levetiracetam vs. Phenobarbital for Seizure Control in Pediatric Cerebral Malaria
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.
Read the 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.
- Conditions
- Seizure, Epilepsy, Cerebral Malaria
- Being tested
- Oral Levetiracetam, Standard AED
- Medical subject headings
- Seizures, Epilepsy, Malaria, Cerebral
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Oral LevetiracetamDrug
Also called Keppra
liquid, 40 mg/kg loading dose and 30mg/kg every 12 hours via nasogastric tube for 3 days
Standard AEDDrug
Also called Standard regimen of AED therapy
Active comparitor, Standard AED
| Study group | Role | What they receive |
|---|---|---|
| Oral Levetiracetam | Experimental | Oral Levetiracetam administered by NG tube. Receives: Drug: Oral Levetiracetam |
| Standard AED | Active comparator | Standard AED regimen Receives: Drug: Standard AED |
What is being measured
The primary outcome is the main question the study is designed to answer.
Minutes With Seizure on EEG
Comparing LVT to standard AED the number of minutes spent in seizure per cEEG in the 72 hours after treatment allocation.
Measured: 72 hours
Secondary outcomes (3)
Required Additional AED
Additional AEDs required (including for breakthrough seizures in LVT group) during admission for seizure control (yes/no)
Measured: 7 days
Mean Time From Admission to BCS >/= 4
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
Measured: 7 days
Sequelae
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
Measured: 7 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Nov 2013 (estimated)
- Study startJan 2014
- Primary completionJun 2015
- Study completionJun 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for SeizureStudies of the same condition, open and under way.
- More trials run by University of RochesterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 44 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Rochester
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Gretchen Birbeck, University of Rochester
- Investigators
- Gretchen L Birbeck, M.D., Principal investigator, University of Rochester
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01982812
- Sponsor's protocol ID
- 7R01NS074409-02
- Other IDs
- R01NS074409
- Acronym
- LVT2
- Status last verified
- Jun 2016
- First submitted
- 5 Nov 2013
- Last updated
- 29 Jul 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: 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.
Publications
Birbeck GL, Herman ST, Capparelli EV, Dzinjalamala FK, Abdel Baki SG, Mallewa M, Toto NM, Postels DG, Gardiner JC, Taylor TE, Seydel KB. A clinical trial of enteral Levetiracetam for acute seizures in pediatric cerebral malaria. BMC Pediatr. 2019 Nov 1;19(1):399. doi: 10.1186/s12887-019-1766-2.
PubMed 31672143
Study at a glance
From the registry record, last updated by the sponsor on 29 Jul 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Safety and Feasibility Study of Enteral Levetiracetam vs. Phenobarbital for Seizure Control in Pediatric Cerebral Malaria
- ClinicalTrials.gov ID
- NCT01982812
- Acronym / sponsor ID
- LVT2 / 7R01NS074409-02
- Conditions
- Seizure, Epilepsy, Cerebral Malaria
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 44 participants (actual)
- Lead sponsor
- University of RochesterUniversity, hospital or other
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS)
- Study start
- Jan 2014
- Primary completion
- Jun 2015 (actual)
- Study completion
- Jun 2015 (actual)
- First posted
- 13 Nov 2013 (estimated)
- Results
- Posted 29 Jul 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Oral Levetiracetam | Experimental | Drug: Oral LevetiracetamOral Levetiracetam administered by NG tube. |
| Standard AED | Active comparator | Drug: Standard AEDStandard AED regimen |
Who may qualify
- Ages
- 24 to 83 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- Comatose with Blantyre Comas Score ≤ 2
- P. falciparum parasitemia via thick blood film or rapid diagnostic test
- Active seizure in past 24 hours
Key exclusion criteria (2 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Oral LevetiracetamAlso: Keppraliquid, 40 mg/kg loading dose and 30mg/kg every 12 hours via nasogastric tube for 3 days | Drug | Oral Levetiracetam |
| Standard AEDAlso: Standard regimen of AED therapyActive comparitor, Standard AED | Drug | Standard AED |
Primary outcome
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.
3 secondary outcomes
Required Additional AED
Time frame: 7 days
Mean Time From Admission to BCS >/= 4
Time frame: 7 days
Sequelae
Time frame: 7 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jul 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 31672143Birbeck GL, Herman ST, Capparelli EV, Dzinjalamala FK, Abdel Baki SG, Mallewa M, Toto NM, Postels DG, Gardiner JC, Taylor TE, Seydel KB. A clinical trial of enteral Levetiracetam for acute seizures in pediatric cerebral malaria. BMC Pediatr. 2019 Nov 1;19(1):399. doi: 10.1186/s12887-019-1766-2.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gretchen L Birbeck, M.D. principal investigator
University of Rochester
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Oral Levetiracetam and Standard AED in people with Seizure and Epilepsy, run by University of Rochester at 1 site in Malawi.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Jul 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Malawi. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Jul 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Minutes With Seizure on EEG (time frame: 72 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01982812, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jul 2016.