EpilepsyPhase 3NCT02726867
Levetiracetam, Lacosamide and Ketamine as Adjunctive Treatment of Refractory Status Epilepticus
A Phase 3 study testing levetiracetam, lacosamide and Ketamine in people with Epilepsy and Status Epilepticus, run by Mid-Atlantic Epilepsy and Sleep Center, LLC at 1 site in United States.
Trial summary
The purpose of the study is to evaluate the efficacy and safety of levetiracetam , lacosamide and ketamine treatment of refractory status epilepticus. This will be a randomized, open-label, four-arm pilot study comparing time to cessation of refractory status epilepticus, determined by continuous EEG monitoring, in… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Epilepsy, Status Epilepticus
- What is being tested?
- levetiracetam, lacosamide and Ketamine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2014to Nov 2016
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18-70
- Ability and willingness by surrogates to signed informed consent form.
- Clinically and electrographically documented ongoing SE lasting ≥1 hour- ≤24 hours
Who cannot join
- Creatinine > 2.5 mg/dl
- Any systemic illness or unstable medical condition that might pose additional risk, including: cardiac, metabolic or endocrine disturbances, renal or liver disease
- Active drug or alcohol dependence or any other factors that, in the opinion of the site investigators would interfere with adherence to study requirements
- Pregnancy
- Inability or unwillingness of subject or legal surrogate to give written informed consent
- Known allergy to a study drug
- Hypo- or hyperglycemia as cause of SE
Trial locations and contacts
1 site in 1 country.
United States1 site
MidAtlantic Epilepsy and Sleep Center
Bethesda, Maryland, 20817
About this study
Official title: Evaluation of Efficacy and Safety of Levetiracetam, Lacosamide and Ketamine as Adjunctive Treatment of Refractory Status Epilepticus
The purpose of the study is to evaluate the efficacy and safety of levetiracetam , lacosamide and ketamine treatment of refractory status epilepticus. This will be a randomized, open-label, four-arm pilot study comparing time to cessation of refractory status epilepticus, determined by continuous EEG monitoring, in patients with refractory status epilepticus. Patients with status epilepticus who have been treated with standard dose lorazepam (or midazolam) and ≥ 1000 mg phenytoin with documented levels of ≥20 mg/ml and continue to have clinical status epilepticus for ≥1-24 hours after phenytoin loading will receive intravenously (i.v.) either 4000 mg levetiracetam, 600 mg lacosamide (Group B), 2.5 mg/kg ketamine or phenobarbital 15 mg/kg phenobarbital (Group D)
Read the detailed description
40 18-70 year old men and women with refractory status epilepticus, defined as status epilepticus continuing for >1 hour after completion of standard treatment with lorazepam (or midazolam) and i.v. phenytoin (or fos-phenytoin),will be enrolled. Participants will be randomized into four treatment arms, levetiracetam 4000 (Group A, n=10), lacosamide 600 mg (Group B, n=10), ketamine 2.5 mg/kg (group C,n=10),and phenobarbital 15 mg/kg (Group D, n=10) in a 1:1:1:1 ratio. Baseline evaluations will include continuous EEG, phenytoin levels prior to study intervention, CBC, CMP, serum Ca, Po4 and Mg.
Treatment will consist of levetiracetam 4000 mg i.v. over 10 minutes, lacosamide 600 mg i.v. over 10 minutes, ketamine 2.5 mg/kg over 10 minutes, or phenobarbital 15 mg/kg mg i.v. at 100 mg/minute rate.
Participants will be evaluated with ongoing physical examination and continuous EEG monitoring. Continuous EEG monitoring will be started before initiation of the study treatment, with documentation of electrographic status epilepticus. It will continue throughout the treatment period. Subjects will be observed for 1 hour clinically and with continuous EEG monitoring for cessation of SE. Participants in whom status epilepticus stops within 60 minutes of completion of study treatment will continue to receive phenytoin (150 mg i.v. q 12 hours, standard dose) and the study medication (levetiracetam 1500 mg i.v. q 12 hourly, lacosamide 300 mg q 12 hourly, ketamine 50 mg qid (vs. 40 mcg/kg/min i.v. infusion, as clinically applicable, or phenobarbital 90 mg i.v. q 12 hourly). Continuous EEG monitoring will continue for 72 hours to monitor for relapse of status epilepticus. Participants in whom status epilepticus fails to stop within 60 minutes after completion of study treatment ("non-responders") will undergo standard treatment with medically-induced coma, with intubation/ventilation and i.v. midazolam or propofol treatment at a dose to be titrated to EEG effect of "burst suppression" or suppression of all background activity. All patients, responders and non-responders alike, will continue treatment with phenytoin i.v., 150 mg q 12 hourly or, for conscious patients, 300 mg p.o. qhs for 72 hours after completion of study treatment. In patients requiring medical coma after study treatments (non-responders), medical coma will be discontinued after 48 hours. All participants will continue to be monitored with continuous EEG for 72 hours from completion of study treatment. If status epilepticus returns during this time, medical coma will be re-instituted and patients will be treated according to standard clinical care for prolonged SE
- Conditions
- Epilepsy, Status Epilepticus
- Being tested
- levetiracetam, lacosamide, Ketamine, Phenobarbital
- Keywords
- refractory status epilepticus, levetiracetam, lacosamide, ketamine
- Medical subject headings
- Epilepsy, Status Epilepticus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
levetiracetamDrug
Also called Keppra
Treatment will consist of LEV 4000 mg i.v. over 10 minutes.
lacosamideDrug
Also called Vimpat
Treatment will consist of LCM 600 mg i.v. over 10 minutes
KetamineDrug
Also called Ketalar
Treatment will consist of KET 2.5 mg/kg over 10 minutes
PhenobarbitalDrug
Also called Phenobarb
Treatment will consist of PHB 15 mg/kg mg i.v. at 100 mg/minute rate
| Study group | Role | What they receive |
|---|---|---|
| levetiracetam | Active comparator | Patients with status epilepticus who have been treated with standard dose lorazepam (or midazolam) and ≥ 1000 mg phenytoin with documented levels of ≥20 mg/ml and continue to have clinical SE for ≥1-24 hours after phenytoin loading will receive intravenously (i.v.) 4000 mg levetiracetam. Receives: Drug: levetiracetam |
| lacosamide | Active comparator | Patients with status epilepticus who have been treated with standard dose lorazepam (or midazolam) and ≥ 1000 mg phenytoin with documented levels of ≥20 mg/ml and continue to have clinical SE for ≥1-24 hours after phenytoin loading will receive intravenously (i.v.) 600 mg lacosamide. Receives: Drug: lacosamide |
| ketamine | Active comparator | Patients with status epilepticus who have been treated with standard dose lorazepam (or midazolam) and ≥ 1000 mg phenytoin with documented levels of ≥20 mg/ml and continue to have clinical SE for ≥1-24 hours after phenytoin loading will receive intravenously (i.v.) 2.5 mg/kg ketamine. Receives: Drug: Ketamine |
| phenobarbital | Active comparator | Patients with status epilepticus who have been treated with standard dose lorazepam (or midazolam) and ≥ 1000 mg phenytoin (PHT) with documented levels of ≥20 mg/ml and continue to have clinical SE for ≥1-24 hours after PHT loading will receive intravenously (i.v.) phenobarbital 15 mg/kg. Receives: Drug: Phenobarbital |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cessation of status epilepticus by EEG.
The cessation of ictal epileptic EEG activity measured by EEG.
Measured: 60 minutes
Secondary outcomes (1)
Cessation of status epilepticus by clinical examination
Measurement of the time to status epilepticus cessation by clinical examination.
Measured: 60 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Apr 2016 (estimated)
- Study startFeb 2014
- Primary completionNov 2016
- Study completionNov 2016
Why it stopped: No participants enrolled
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for EpilepsyStudies of the same condition, open and under way.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mid-Atlantic Epilepsy and Sleep Center, LLC
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Pavel Klein, Mid-Atlantic Epilepsy and Sleep Center, LLC
- Investigators
- Pavel Klein, M.D., Principal investigator, Mid-Atlantic Epilepsy and Sleep Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02726867
- Sponsor's protocol ID
- MAES-003
- Status last verified
- Aug 2017
- First submitted
- 12 Dec 2014
- Last updated
- 29 Aug 2017
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Efficacy and Safety of Levetiracetam, Lacosamide and Ketamine as Adjunctive Treatment of Refractory Status Epilepticus
- ClinicalTrials.gov ID
- NCT02726867
- Acronym / sponsor ID
- MAES-003
- Conditions
- Epilepsy, Status Epilepticus
- Keywords
- refractory status epilepticus, levetiracetam, lacosamide, ketamine
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: No participants enrolled
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Mid-Atlantic Epilepsy and Sleep Center, LLCUniversity, hospital or other
- Study start
- Feb 2014
- Primary completion
- Nov 2016 (actual)
- Study completion
- Nov 2016 (actual)
- First posted
- 4 Apr 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of the study is to evaluate the efficacy and safety of levetiracetam , lacosamide and ketamine treatment of refractory status epilepticus. This will be a randomized, open-label, four-arm pilot study comparing time to cessation of refractory status epilepticus, determined by continuous EEG monitoring, in patients with refractory status epilepticus. Patients with status epilepticus who have been treated with standard dose lorazepam (or midazolam) and ≥ 1000 mg phenytoin with documented levels of ≥20 mg/ml and continue to have clinical status epilepticus for ≥1-24 hours after phenytoin loading will receive intravenously (i.v.) either 4000 mg levetiracetam, 600 mg lacosamide (Group B), 2.5 mg/kg ketamine or phenobarbital 15 mg/kg phenobarbital (Group D)
Detailed description
40 18-70 year old men and women with refractory status epilepticus, defined as status epilepticus continuing for >1 hour after completion of standard treatment with lorazepam (or midazolam) and i.v. phenytoin (or fos-phenytoin),will be enrolled. Participants will be randomized into four treatment arms, levetiracetam 4000 (Group A, n=10), lacosamide 600 mg (Group B, n=10), ketamine 2.5 mg/kg (group C,n=10),and phenobarbital 15 mg/kg (Group D, n=10) in a 1:1:1:1 ratio. Baseline evaluations will include continuous EEG, phenytoin levels prior to study intervention, CBC, CMP, serum Ca, Po4 and Mg.
Treatment will consist of levetiracetam 4000 mg i.v. over 10 minutes, lacosamide 600 mg i.v. over 10 minutes, ketamine 2.5 mg/kg over 10 minutes, or phenobarbital 15 mg/kg mg i.v. at 100 mg/minute rate.
Participants will be evaluated with ongoing physical examination and continuous EEG monitoring. Continuous EEG monitoring will be started before initiation of the study treatment, with documentation of electrographic status epilepticus. It will continue throughout the treatment period. Subjects will be observed for 1 hour clinically and with continuous EEG monitoring for cessation of SE. Participants in whom status epilepticus stops within 60 minutes of completion of study treatment will continue to receive phenytoin (150 mg i.v. q 12 hours, standard dose) and the study medication (levetiracetam 1500 mg i.v. q 12 hourly, lacosamide 300 mg q 12 hourly, ketamine 50 mg qid (vs. 40 mcg/kg/min i.v. infusion, as clinically applicable, or phenobarbital 90 mg i.v. q 12 hourly). Continuous EEG monitoring will continue for 72 hours to monitor for relapse of status epilepticus. Participants in whom status epilepticus fails to stop within 60 minutes after completion of study treatment ("non-responders") will undergo standard treatment with medically-induced coma, with intubation/ventilation and i.v. midazolam or propofol treatment at a dose to be titrated to EEG effect of "burst suppression" or suppression of all background activity. All patients, responders and non-responders alike, will continue treatment with phenytoin i.v., 150 mg q 12 hourly or, for conscious patients, 300 mg p.o. qhs for 72 hours after completion of study treatment. In patients requiring medical coma after study treatments (non-responders), medical coma will be discontinued after 48 hours. All participants will continue to be monitored with continuous EEG for 72 hours from completion of study treatment. If status epilepticus returns during this time, medical coma will be re-instituted and patients will be treated according to standard clinical care for prolonged SE
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| levetiracetam | Active comparator | Drug: levetiracetamPatients with status epilepticus who have been treated with standard dose lorazepam (or midazolam) and ≥ 1000 mg phenytoin with documented levels of ≥20 mg/ml and continue to have clinical SE for ≥1-24 hours after phenytoin loading will receive intravenously (i.v.) 4000 mg levetiracetam. |
| lacosamide | Active comparator | Drug: lacosamidePatients with status epilepticus who have been treated with standard dose lorazepam (or midazolam) and ≥ 1000 mg phenytoin with documented levels of ≥20 mg/ml and continue to have clinical SE for ≥1-24 hours after phenytoin loading will receive intravenously (i.v.) 600 mg lacosamide. |
| ketamine | Active comparator | Drug: KetaminePatients with status epilepticus who have been treated with standard dose lorazepam (or midazolam) and ≥ 1000 mg phenytoin with documented levels of ≥20 mg/ml and continue to have clinical SE for ≥1-24 hours after phenytoin loading will receive intravenously (i.v.) 2.5 mg/kg ketamine. |
| phenobarbital | Active comparator | Drug: PhenobarbitalPatients with status epilepticus who have been treated with standard dose lorazepam (or midazolam) and ≥ 1000 mg phenytoin (PHT) with documented levels of ≥20 mg/ml and continue to have clinical SE for ≥1-24 hours after PHT loading will receive intravenously (i.v.) phenobarbital 15 mg/kg. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Age 18-70
- Ability and willingness by surrogates to signed informed consent form.
- Clinically and electrographically documented ongoing SE lasting ≥1 hour- ≤24 hours
Key exclusion criteria (7 listed)
- Creatinine > 2.5 mg/dl
- Any systemic illness or unstable medical condition that might pose additional risk, including: cardiac, metabolic or endocrine disturbances, renal or liver disease
- Active drug or alcohol dependence or any other factors that, in the opinion of the site investigators would interfere with adherence to study requirements
- Pregnancy
- Inability or unwillingness of subject or legal surrogate to give written informed consent
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 |
|---|---|---|
| levetiracetamAlso: KeppraTreatment will consist of LEV 4000 mg i.v. over 10 minutes. | Drug | levetiracetam |
| lacosamideAlso: VimpatTreatment will consist of LCM 600 mg i.v. over 10 minutes | Drug | lacosamide |
| KetamineAlso: KetalarTreatment will consist of KET 2.5 mg/kg over 10 minutes | Drug | ketamine |
| PhenobarbitalAlso: PhenobarbTreatment will consist of PHB 15 mg/kg mg i.v. at 100 mg/minute rate | Drug | phenobarbital |
Primary outcome
Cessation of status epilepticus by EEG.
Time frame: 60 minutes
The cessation of ictal epileptic EEG activity measured by EEG.
1 secondary outcome
Cessation of status epilepticus by clinical examination
Time frame: 60 minutes
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Aug 2017.
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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.
Pavel Klein, M.D. principal investigator
Mid-Atlantic Epilepsy and Sleep Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing levetiracetam, lacosamide and Ketamine in people with Epilepsy and Status Epilepticus, run by Mid-Atlantic Epilepsy and Sleep Center, LLC at 1 site in United States.
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 7 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: withdrawn, as of the sponsor's last update on 29 Aug 2017. 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 United States. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
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?
Cessation of status epilepticus by EEG. (time frame: 60 minutes). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 Aug 2017.