Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Ketamine for Thrombolysis in Acute Ischemic Stroke (KETA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02258204
Recruitment Status : Unknown
Verified February 2016 by Emmanuel TOUZE, University Hospital, Caen.
Recruitment status was:  Recruiting
First Posted : October 7, 2014
Last Update Posted : February 24, 2016
Sponsor:
Collaborators:
Société Française d'Anesthésie Réanimation
Fondation NRJ
Information provided by (Responsible Party):
Emmanuel TOUZE, University Hospital, Caen

Brief 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 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.

Condition or disease Intervention/treatment Phase
Stroke Drug: Ketamine Drug: Placebo Phase 1 Phase 2

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Study Start Date : March 2015
Estimated Primary Completion Date : December 2017
Estimated Study Completion Date : February 2018

Resource links provided by the National Library of Medicine

Drug Information available for: Ketamine

Arm Intervention/treatment
Placebo Comparator: tPA-placebo

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).

Drug: Placebo
Experimental: tPA-ketamine

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).

Drug: Ketamine
Co-administration of subanesthetic dose of ketamine with tPA for thrombolysis in acute ischemic stroke.




Primary Outcome Measures :
  1. Cerebral infarction growth on diffusion weighted magnetic resonance imaging between admission and day 1. [ Time Frame: Day 1 ]

Secondary Outcome Measures :
  1. National Institute of Health Stroke Scale [ Time Frame: day 0, day 1, day 7 and day 90 ]
  2. Modified Rankin Scale [ Time Frame: day 90 ]
  3. Infarction volume on diffusion weighted magnetic resonance imaging [ Time Frame: day 1 ]
  4. T2-weighted Fluid Attenuated Inversion Recovery Imaging infarct volume [ Time Frame: day 90 ]
  5. Symptomatic intracerebral hemorrhage and/or death [ Time Frame: day 90 ]
  6. Arterial patency [ Time Frame: day 0 (before and after thrombectomy) and day 1 ]
    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).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.
  • 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.

Exclusion Criteria:

  • 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.
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02258204


Locations
Layout table for location information
France
CHU Caen Recruiting
Caen, France
Contact: Emmanuel Touzé, MD PhD    +33231064624    touze-e@chu-caen.fr   
Sponsors and Collaborators
University Hospital, Caen
Société Française d'Anesthésie Réanimation
Fondation NRJ
Publications:
Layout table for additonal information
Responsible Party: Emmanuel TOUZE, Professor, University Hospital, Caen
ClinicalTrials.gov Identifier: NCT02258204    
Other Study ID Numbers: KETA
First Posted: October 7, 2014    Key Record Dates
Last Update Posted: February 24, 2016
Last Verified: February 2016
Keywords provided by Emmanuel TOUZE, University Hospital, Caen:
Cerebral Infarct
Thrombolysis
Tissue-type plasminogen activator
Neuroprotection
Anesthetic agent
Magnetic resonance imaging
Additional relevant MeSH terms:
Layout table for MeSH terms
Stroke
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Ketamine
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anesthetics, Dissociative
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
Central Nervous System Depressants
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action