Refractory EpilepsyPhase 2/3NCT03115489
Efficacy of Ketamine Infusion Compared With Traditional Anti-epileptic Agents in Refractory Status Epilepticus
A Phase 2/3 study testing Traditional Treatment (Group T) and Ketamine Infusion (Group K) in people with Refractory Epilepsy, run by University of Alabama at Birmingham at 1 site in United States.
Trial summary
The study will investigate the efficacy of the N-methyl-D-aspartate receptor antagonist ketamine as a first line agent in refractory status epilepticus versus traditional general anesthetic agents used for burst suppression that target the gamma-aminobutyric acid adrenergic receptors. Read more about this study
- Who is it for?
- Ages 18 to 100 yearsHealthy volunteers can take part
- Conditions the study is for
- Refractory Epilepsy
- What is being tested?
- Traditional Treatment (Group T) and Ketamine Infusion (Group K)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 4 May 2017to 18 May 2021
- Phase
- Phase 2/3
- 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 100 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Patients more than 18 years of age with a diagnosis of status epilepticus
- Considered for burst suppression therapy after failing 2 or 3 anti-epileptic medications
Who cannot join
- Post anoxic status epilepticus
- Pregnant women, as confirmed by urine, or blood human chorionic gonadotropin, ultrasound or physical exam
- Prisoners
- Age less than 18 years
- Allergy or sensitivity to the drug in question
Trial locations and contacts
1 site in 1 country.
United States1 site
UAB Department of Anesthesiology and Perioperative Medicine
Birmingham, Alabama, 35249
About this study
Official title: Efficacy of Ketamine Infusion Compared With Traditional Anti-epileptic Agents in Refractory Status Epilepticus- a Pilot Study
The study will investigate the efficacy of the N-methyl-D-aspartate receptor antagonist ketamine as a first line agent in refractory status epilepticus versus traditional general anesthetic agents used for burst suppression that target the gamma-aminobutyric acid adrenergic receptors.
Read the detailed description
The traditional treatment for refractory status epilepticus includes diazepam, midazolam, valproic acid, thiopental and propofol. These medications fail to control seizure activity in 20-40% of patients. This is attributed to decrease in activity of gamma-aminobutyric acid receptors along with reciprocal up regulation of N-Methyl-D-aspartate receptors. Glutamate activation of N-methyl-D-aspartate receptors promotes calcium influx and excitotoxicity. Ketamine, an intravenous anesthetic agent which is a non-competitive antagonist of N-methyl-D-aspartate receptors can block the flow of Ca and Na and by combining with phencyclidine binding sites inside the ion channel of N-methyl-D-aspartate receptors, reduce the epileptiform burst discharges and after potential. Therefore, targeting the N-methyl-D-aspartate receptors with ketamine may provide a novel approach to control refractory seizures. Moreover, by blocking glutamate mediated N-methyl-D-aspartate receptor induced neurotoxicity, ketamine may render neuroprotection. Ketamine also provides additional advantage of hemodynamic stability. Currently, ketamine is used as a last resort drug in the treatment of refractory status epilepticus.
The specific aim is to determine whether continuous infusion of ketamine as a first line agent for refractory status epilepticus is effective in controlling seizures.
The central hypothesis of our proposal is that early treatment with ketamine will be much more efficacious in controlling refractory status compared to the traditional treatment.
- Conditions
- Refractory Epilepsy
- Being tested
- Traditional Treatment (Group T), Ketamine Infusion (Group K)
- Keywords
- seizure, glutamate activation, N-Methyl D-Aspartate, gamma-aminobutyric acid receptor, Ketamine
- Medical subject headings
- Drug Resistant Epilepsy, Seizures
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Traditional Treatment (Group T)Drug
Also called benzodiazepines, barbiturates, propofol
Patients will receive traditional drug infusions
Ketamine Infusion (Group K)Drug
Also called Ketalar
Patients will receive loading dose of 2.5 mg/kg of ketamine followed by a continuous infusion with a starting dose of 3mg/kg/hr with titration in 1mg/kg/hr increments until burst suppression is achieved or a maximum dose of 10mg/kg/hr is reached
| Study group | Role | What they receive |
|---|---|---|
| Traditional Treatment (Group T) | Placebo comparator | Group T patients will be placed into burst suppression with the traditional drug infusions which include any single or combination of drugs; usually benzodiazepines, barbiturates and or propofol. Receives: Drug: Traditional Treatment (Group T) |
| Ketamine Infusion (Group K) | Active comparator | Patients in the group K arm will receive a loading dose of 2.5 mg/kg of ketamine followed by a continuous infusion with a starting dose of 3mg/kg/hr with titration in 1mg/kg/hr increments until burst suppression is achieved or a maximum dose of 10mg/kg/hr is reached. After 48 hours of burst suppression the ketamine dosage will be reduced by 2mg/kg/hr in a stepwise fashion to evaluated for EEG or clinical evidence of seizure recurrence. Receives: Drug: Ketamine Infusion (Group K) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time taken for burst suppression
Average time for burst suppression
Measured: Baseline to 1 hr
Time taken for termination of seizures
Average time for seizures to terminate
Measured: Baseline to 24 hrs
Secondary outcomes (6)
Use of vasopressors
The need of vasopressors
Measured: baseline to 72 hrs
Number of days on ventilator
Total number of days patient is on the ventilator
Measured: Baseline to 72 hrs
Length of stay in ICU
Total number of days in the ICU
Measured: Baseline to 72 hrs postoperatively
Use of parenteral or enteral nutrition
Nutrition provided through a feeding tube or catheter
Measured: Baseline to 72 hrs postoperatively
Medical imaging results
MRI scans 7 to 10 days after burst suppression
Measured: Post-op Day 2 to Post-op day 10
Mortality
death
Measured: baseline to post-op day 10
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Apr 2017
- Study start4 May 2017
- Primary completion31 Dec 2019
- Study completion18 May 2021
Why it stopped: Low eligibility of patients, no successful recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Refractory EpilepsyStudies of the same condition, open and under way.
- More trials run by University of Alabama at BirminghamThe 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 2/3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Alabama at Birmingham
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Vinodkumar Singh, University of Alabama at Birmingham
- Investigators
- Vinodkumar Singh, MD, Principal investigator, University of Alabama at Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03115489
- Sponsor's protocol ID
- F151214004
- Status last verified
- May 2021
- First submitted
- 10 Apr 2017
- Last updated
- 21 May 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Rosati A, De Masi S, Guerrini R. Ketamine for Refractory Status Epilepticus: A Systematic Review. CNS Drugs. 2018 Nov;32(11):997-1009. doi: 10.1007/s40263-018-0569-6.
PubMed 30232735
Study at a glance
From the registry record, last updated by the sponsor on 21 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of Ketamine Infusion Compared With Traditional Anti-epileptic Agents in Refractory Status Epilepticus- a Pilot Study
- ClinicalTrials.gov ID
- NCT03115489
- Acronym / sponsor ID
- F151214004
- Conditions
- Refractory Epilepsy
- Keywords
- seizure, glutamate activation, N-Methyl D-Aspartate, gamma-aminobutyric acid receptor, Ketamine
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Low eligibility of patients, no successful recruitment
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of Alabama at BirminghamUniversity, hospital or other
- Study start
- 4 May 2017 (actual)
- Primary completion
- 31 Dec 2019 (actual)
- Study completion
- 18 May 2021 (actual)
- First posted
- 14 Apr 2017 (actual)
- 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 study will investigate the efficacy of the N-methyl-D-aspartate receptor antagonist ketamine as a first line agent in refractory status epilepticus versus traditional general anesthetic agents used for burst suppression that target the gamma-aminobutyric acid adrenergic receptors.
Detailed description
The traditional treatment for refractory status epilepticus includes diazepam, midazolam, valproic acid, thiopental and propofol. These medications fail to control seizure activity in 20-40% of patients. This is attributed to decrease in activity of gamma-aminobutyric acid receptors along with reciprocal up regulation of N-Methyl-D-aspartate receptors. Glutamate activation of N-methyl-D-aspartate receptors promotes calcium influx and excitotoxicity. Ketamine, an intravenous anesthetic agent which is a non-competitive antagonist of N-methyl-D-aspartate receptors can block the flow of Ca and Na and by combining with phencyclidine binding sites inside the ion channel of N-methyl-D-aspartate receptors, reduce the epileptiform burst discharges and after potential. Therefore, targeting the N-methyl-D-aspartate receptors with ketamine may provide a novel approach to control refractory seizures. Moreover, by blocking glutamate mediated N-methyl-D-aspartate receptor induced neurotoxicity, ketamine may render neuroprotection. Ketamine also provides additional advantage of hemodynamic stability. Currently, ketamine is used as a last resort drug in the treatment of refractory status epilepticus.
The specific aim is to determine whether continuous infusion of ketamine as a first line agent for refractory status epilepticus is effective in controlling seizures.
The central hypothesis of our proposal is that early treatment with ketamine will be much more efficacious in controlling refractory status compared to the traditional treatment.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Traditional Treatment (Group T) | Placebo comparator | Drug: Traditional Treatment (Group T)Group T patients will be placed into burst suppression with the traditional drug infusions which include any single or combination of drugs; usually benzodiazepines, barbiturates and or propofol. |
| Ketamine Infusion (Group K) | Active comparator | Drug: Ketamine Infusion (Group K)Patients in the group K arm will receive a loading dose of 2.5 mg/kg of ketamine followed by a continuous infusion with a starting dose of 3mg/kg/hr with titration in 1mg/kg/hr increments until burst suppression is achieved or a maximum dose of 10mg/kg/hr is reached. After 48 hours of burst suppression the ketamine dosage will be reduced by 2mg/kg/hr in a stepwise fashion to evaluated for EEG or clinical evidence of seizure recurrence. |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Patients more than 18 years of age with a diagnosis of status epilepticus
- Considered for burst suppression therapy after failing 2 or 3 anti-epileptic medications
Key exclusion criteria (5 listed)
- Post anoxic status epilepticus
- Pregnant women, as confirmed by urine, or blood human chorionic gonadotropin, ultrasound or physical exam
- Prisoners
- Age less than 18 years
- Allergy or sensitivity to the drug in question
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 |
|---|---|---|
| Traditional Treatment (Group T)Also: benzodiazepines, barbiturates, propofolPatients will receive traditional drug infusions | Drug | Traditional Treatment (Group T) |
| Ketamine Infusion (Group K)Also: KetalarPatients will receive loading dose of 2.5 mg/kg of ketamine followed by a continuous infusion with a starting dose of 3mg/kg/hr with titration in 1mg/kg/hr increments until burst suppression is achieved or a maximum dose of 10mg/kg/hr is reached | Drug | Ketamine Infusion (Group K) |
Primary outcome
Time taken for burst suppression
Time frame: Baseline to 1 hr
Average time for burst suppression
Time taken for termination of seizures
Time frame: Baseline to 24 hrs
Average time for seizures to terminate
6 secondary outcomes
Use of vasopressors
Time frame: baseline to 72 hrs
Number of days on ventilator
Time frame: Baseline to 72 hrs
Length of stay in ICU
Time frame: Baseline to 72 hrs postoperatively
Use of parenteral or enteral nutrition
Time frame: Baseline to 72 hrs postoperatively
Medical imaging results
Time frame: Post-op Day 2 to Post-op day 10
Mortality
Time frame: baseline to post-op day 10
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 21 May 2021.
- Derived from this study: PubMed 30232735Rosati A, De Masi S, Guerrini R. Ketamine for Refractory Status Epilepticus: A Systematic Review. CNS Drugs. 2018 Nov;32(11):997-1009. doi: 10.1007/s40263-018-0569-6.
- Individual participant dataSharing planned: No
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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.
Vinodkumar Singh, MD principal investigator
University of Alabama at Birmingham
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Traditional Treatment (Group T) and Ketamine Infusion (Group K) in people with Refractory Epilepsy, run by University of Alabama at Birmingham 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 2 inclusion and 5 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 21 May 2021. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined 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.
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?
Time taken for burst suppression (time frame: Baseline to 1 hr). The study lists 2 primary outcomes in all. 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 NCT03115489, 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 21 May 2021.