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Ketamine for Thrombolysis in Acute Ischemic Stroke (KETA)

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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

Tracking Information
First Submitted Date  ICMJE October 3, 2014
First Posted Date  ICMJE October 7, 2014
Last Update Posted Date February 24, 2016
Study Start Date  ICMJE March 2015
Estimated Primary Completion Date December 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 6, 2014)
Cerebral infarction growth on diffusion weighted magnetic resonance imaging between admission and day 1. [ Time Frame: Day 1 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 23, 2016)
  • 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 ]
    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).
Original Secondary Outcome Measures  ICMJE
 (submitted: October 6, 2014)
  • National Institute of Health Stroke Scale [ Time Frame: 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 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Ketamine for Thrombolysis in Acute Ischemic Stroke
Official Title  ICMJE 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
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.
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Stroke
Intervention  ICMJE
  • Drug: Ketamine
    Co-administration of subanesthetic dose of ketamine with tPA for thrombolysis in acute ischemic stroke.
  • Drug: Placebo
Study Arms  ICMJE
  • 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).

    Intervention: 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).

    Intervention: Drug: Ketamine
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: October 6, 2014)
50
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE February 2018
Estimated Primary Completion Date December 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 85 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02258204
Other Study ID Numbers  ICMJE KETA
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Emmanuel TOUZE, University Hospital, Caen
Study Sponsor  ICMJE University Hospital, Caen
Collaborators  ICMJE
  • Société Française d'Anesthésie Réanimation
  • Fondation NRJ
Investigators  ICMJE Not Provided
PRS Account University Hospital, Caen
Verification Date February 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP