StrokePhase 1/2KETANCT02258204
Ketamine for Thrombolysis in Acute Ischemic Stroke
A Phase 1/2 study testing Ketamine in people with Stroke, run by University Hospital, Caen at 1 site in France.
Trial summary
KETA trial is a nonprofit, double-blind, randomized, controlled pilot trial with aiming to determine if co-administration of ketamine with recombinant of tissue type plasminogen activator (tPA) for thrombolysis in acute ischemic stroke compared with tPA co-administered with placebo, decreases cerebral infarction… Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Stroke
- What is being tested?
- Ketamine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 1 siteFrance
- Study dates
- Mar 2015to Feb 2018
- Phase
- Phase 1/2
- 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 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Sudden focal neurological deficit attributable to acute ischemic stroke.
- Age between 18 and 85.
- Time from symptom onset less than 4.5 hours.
- NIHSS score between 7 and 20.
- Informed consent for participation.
- Ketamine can be administered within 15 minutes after onset of tPA infusion.
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- MRI-based AIS diagnosis.
- Middle cerebral (M1 or M2 segment) and/or distal internal carotid artery occlusion.
- No intracranial hemorrhage on MRI.
- Patient eligible for thrombectomy.
Who cannot join
- Contraindication to IV tPA treatment.
- Contraindication to ketamine.
- Contraindication to MRI.
- Contraindication to intravascular iodinated contrast media.
- Consciousness level >1 on question 1a of NIHSS.
- Pre-stroke mRS ≥3.
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- Concomitant medical illness that would interfere with outcome assessments and follow-up (e.g. advanced cancer or respiratory disease).
- Previous participation in this trial or current participation in another investigational drug trial.
- Infarct volume on diffusion weighted MRI more than 100 mL.
Trial locations and contacts
1 site in 1 country.
France1 site, 1 recruiting
- Recruiting
CHU Caen
Caen
Emmanuel Touzé, MD PhD, +33231064624, touze-e@chu-caen.fr
About this study
Official title: Effets de la kétamine en Association Avec le Rt-PA au Cours de l'Infarctus cérébral Aigu: étude Pilote contrôlée randomisée en Double Aveugle Avec critère de Jugement Radiologique
KETA trial is a nonprofit, double-blind, randomized, controlled pilot trial with aiming to determine if co-administration of ketamine with recombinant of tissue type plasminogen activator (tPA) for thrombolysis in acute ischemic stroke compared with tPA co-administered with placebo, decreases cerebral infarction growth in diffusion weighted imaging between admission and day 1. Eligibility applies to patients with symptomatic ischemic stroke seen within 4.5 h of onset with middle cerebral artery or distal internal carotid artery occlusion, no contraindication to intravenous tPA-mediated thrombolysis and eligible to endovascular treatment of stroke (i.e. thrombectomy). The study has been designed to have 80% power to detect a 80% decrease of infarct volume growth in the tPA-ketamine group at a two-sided type I error rate of 5%. For this purpose, at least 25 patients per arm should be enrolled.
Read the detailed description
Rationale - Tissue-type plasminogen activator (tPA) is a double-sided molecule, with beneficial effect in acute ischemic stroke due to its intravascular fibrinolytic activity but with potential deleterious effect due to its ability to potentiate neuronal N-methyl-D-aspartate (NMDA) receptor signalling (Nicole et al., 2001). Co-administration of sub-anesthetic dose of ketamine - a non-competitive inhibitor of NMDA receptor - was shown to improve efficacy of tPA-mediated thrombolysis following stroke in rodents (Gakuba et al, 2011).
Aims - To assess efficacy and safety of co-administration of ketamine with tPA compared with tPA-placebo infusion in patients with acute ischemic stroke.
Sample size estimates -With 25 patients per group, the trial has a 80% probability of detecting a 80% decrease of infarct volume growth in the tPA-ketamine group compared with the tPA-placebo group on day 1 after admission at a two-sided type I error rate of 5%.
Study outcomes - The primary efficacy outcome is cerebral infarction growth on diffusion weighted imaging between admission and day 1. The primary safety measure is mortality and/or symptomatic intracerebral hemorrhage rate at 3 months.
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KetamineDrug
Co-administration of subanesthetic dose of ketamine with tPA for thrombolysis in acute ischemic stroke.
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| tPA-placebo | Placebo comparator | tPA infusion : 0.9 mg/kg (90 mg maximum), 10% of the total dose is administered as an initial IV bolus dose over 1 minute and the remainder of the dose is infused over 60 minutes.
Saline infusion : 0.15 mL/kg IV bolus (maximum 15 mL) followed by an IV infusion of 0.15 mL/kg over 60 minutes (maximum 15 mL). Receives: Drug: Placebo |
| tPA-ketamine | Experimental | tPA infusion : 0.9 mg/kg (90 mg maximum), 10% of the total dose is administered as an initial IV bolus dose over 1 minute and the remainder of the dose is infused over 60 minutes.
Ketamine infusion : 0.15 mg/kg IV bolus (maximum 15 mg) followed by an IV infusion of 0.15 mg/kg over 60 minutes (maximum 15 mg). Receives: Drug: Ketamine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cerebral infarction growth on diffusion weighted magnetic resonance imaging between admission and day 1.
Measured: Day 1
Secondary outcomes (6)
National Institute of Health Stroke Scale
Measured: day 0, day 1, day 7 and day 90
Modified Rankin Scale
Measured: day 90
Infarction volume on diffusion weighted magnetic resonance imaging
Measured: day 1
T2-weighted Fluid Attenuated Inversion Recovery Imaging infarct volume
Measured: day 90
Symptomatic intracerebral hemorrhage and/or death
Measured: day 90
Arterial patency
Arterial patency will be assessed with the Thrombolysis in Cerebral Infarction (TICI) Score on day 0 before and after thrombectomy (digital subtraction angiography) and day 1 (magnetic resonance angiography).
Measured: day 0 (before and after thrombectomy) and day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Oct 2014 (estimated)
- Study startMar 2015
- Primary completionDec 2017 (estimated)
- Study completionFeb 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for StrokeStudies of the same condition, open and under way.
- More trials run by University Hospital, CaenThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Caen
- Sponsor type
- University, hospital or other
- Collaborators
- Société Française d'Anesthésie et de Réanimation, Fondation NRJ
- Responsible party
- Principal investigator, Emmanuel TOUZE, University Hospital, Caen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02258204
- Sponsor's protocol ID
- KETA
- Acronym
- KETA
- Status last verified
- Feb 2016
- First submitted
- 3 Oct 2014
- Last updated
- 24 Feb 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Nicole O, Docagne F, Ali C, Margaill I, Carmeliet P, MacKenzie ET, Vivien D, Buisson A. The proteolytic activity of tissue-plasminogen activator enhances NMDA receptor-mediated signaling. Nat Med. 2001 Jan;7(1):59-64. doi: 10.1038/83358.
PubMed 11135617Gakuba C, Gauberti M, Mazighi M, Defer G, Hanouz JL, Vivien D. Preclinical evidence toward the use of ketamine for recombinant tissue-type plasminogen activator-mediated thrombolysis under anesthesia or sedation. Stroke. 2011 Oct;42(10):2947-9. doi: 10.1161/STROKEAHA.111.620468. Epub 2011 Aug 4.
PubMed 21817137
Study at a glance
From the registry record, last updated by the sponsor on 24 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effets de la kétamine en Association Avec le Rt-PA au Cours de l'Infarctus cérébral Aigu: étude Pilote contrôlée randomisée en Double Aveugle Avec critère de Jugement Radiologique
- ClinicalTrials.gov ID
- NCT02258204
- Acronym / sponsor ID
- KETA / KETA
- Conditions
- Stroke
- Keywords
- Cerebral Infarct, Thrombolysis, Tissue-type plasminogen activator, Neuroprotection, Anesthetic agent, Magnetic resonance imaging
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- University Hospital, CaenUniversity, hospital or other
- Collaborators
- Société Française d'Anesthésie et de Réanimation, Fondation NRJ
- Study start
- Mar 2015
- Primary completion
- Dec 2017 (estimated)
- Study completion
- Feb 2018 (estimated)
- First posted
- 7 Oct 2014 (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.
KETA trial is a nonprofit, double-blind, randomized, controlled pilot trial with aiming to determine if co-administration of ketamine with recombinant of tissue type plasminogen activator (tPA) for thrombolysis in acute ischemic stroke compared with tPA co-administered with placebo, decreases cerebral infarction growth in diffusion weighted imaging between admission and day 1. Eligibility applies to patients with symptomatic ischemic stroke seen within 4.5 h of onset with middle cerebral artery or distal internal carotid artery occlusion, no contraindication to intravenous tPA-mediated thrombolysis and eligible to endovascular treatment of stroke (i.e. thrombectomy). The study has been designed to have 80% power to detect a 80% decrease of infarct volume growth in the tPA-ketamine group at a two-sided type I error rate of 5%. For this purpose, at least 25 patients per arm should be enrolled.
Detailed description
Rationale - Tissue-type plasminogen activator (tPA) is a double-sided molecule, with beneficial effect in acute ischemic stroke due to its intravascular fibrinolytic activity but with potential deleterious effect due to its ability to potentiate neuronal N-methyl-D-aspartate (NMDA) receptor signalling (Nicole et al., 2001). Co-administration of sub-anesthetic dose of ketamine - a non-competitive inhibitor of NMDA receptor - was shown to improve efficacy of tPA-mediated thrombolysis following stroke in rodents (Gakuba et al, 2011).
Aims - To assess efficacy and safety of co-administration of ketamine with tPA compared with tPA-placebo infusion in patients with acute ischemic stroke.
Sample size estimates -With 25 patients per group, the trial has a 80% probability of detecting a 80% decrease of infarct volume growth in the tPA-ketamine group compared with the tPA-placebo group on day 1 after admission at a two-sided type I error rate of 5%.
Study outcomes - The primary efficacy outcome is cerebral infarction growth on diffusion weighted imaging between admission and day 1. The primary safety measure is mortality and/or symptomatic intracerebral hemorrhage rate at 3 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| tPA-placebo | Placebo comparator | Drug: PlacebotPA infusion : 0.9 mg/kg (90 mg maximum), 10% of the total dose is administered as an initial IV bolus dose over 1 minute and the remainder of the dose is infused over 60 minutes. Saline infusion : 0.15 mL/kg IV bolus (maximum 15 mL) followed by an IV infusion of 0.15 mL/kg over 60 minutes (maximum 15 mL). |
| tPA-ketamine | Experimental | Drug: KetaminetPA infusion : 0.9 mg/kg (90 mg maximum), 10% of the total dose is administered as an initial IV bolus dose over 1 minute and the remainder of the dose is infused over 60 minutes. Ketamine infusion : 0.15 mg/kg IV bolus (maximum 15 mg) followed by an IV infusion of 0.15 mg/kg over 60 minutes (maximum 15 mg). |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Sudden focal neurological deficit attributable to acute ischemic stroke.
- Age between 18 and 85.
- Time from symptom onset less than 4.5 hours.
- NIHSS score between 7 and 20.
- Informed consent for participation.
Key exclusion criteria (9 listed)
- Contraindication to IV tPA treatment.
- Contraindication to ketamine.
- Contraindication to MRI.
- Contraindication to intravascular iodinated contrast media.
- Consciousness level >1 on question 1a of NIHSS.
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 |
|---|---|---|
| KetamineCo-administration of subanesthetic dose of ketamine with tPA for thrombolysis in acute ischemic stroke. | Drug | tPA-ketamine |
| Placebo | Drug | tPA-placebo |
Primary outcome
Cerebral infarction growth on diffusion weighted magnetic resonance imaging between admission and day 1.
Time frame: Day 1
6 secondary outcomes
National Institute of Health Stroke Scale
Time frame: day 0, day 1, day 7 and day 90
Modified Rankin Scale
Time frame: day 90
Infarction volume on diffusion weighted magnetic resonance imaging
Time frame: day 1
T2-weighted Fluid Attenuated Inversion Recovery Imaging infarct volume
Time frame: day 90
Symptomatic intracerebral hemorrhage and/or death
Time frame: day 90
Arterial patency
Time frame: day 0 (before and after thrombectomy) and day 1
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Feb 2016.
- Background: PubMed 11135617Nicole O, Docagne F, Ali C, Margaill I, Carmeliet P, MacKenzie ET, Vivien D, Buisson A. The proteolytic activity of tissue-plasminogen activator enhances NMDA receptor-mediated signaling. Nat Med. 2001 Jan;7(1):59-64. doi: 10.1038/83358.
- Background: PubMed 21817137Gakuba C, Gauberti M, Mazighi M, Defer G, Hanouz JL, Vivien D. Preclinical evidence toward the use of ketamine for recombinant tissue-type plasminogen activator-mediated thrombolysis under anesthesia or sedation. Stroke. 2011 Oct;42(10):2947-9. doi: 10.1161/STROKEAHA.111.620468. Epub 2011 Aug 4.
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Ketamine in people with Stroke, run by University Hospital, Caen at 1 site in France.
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 10 inclusion and 9 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: status not confirmed, as of the sponsor's last update on 24 Feb 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 France. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cerebral infarction growth on diffusion weighted magnetic resonance imaging between admission and day 1. (time frame: Day 1). 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 NCT02258204, which also lists 2 linked publications.
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 24 Feb 2016.