Back to results

Ketamine for Thrombolysis in Acute Ischemic Stroke (KETA)

Primary Purpose

Stroke

Status

Unknown status

Phase

Phase 1

Locations

France

Study Type

Interventional

Intervention

Ketamine

Placebo

About this trial

This is an interventional treatment trial for Stroke focused on measuring Cerebral Infarct, Thrombolysis, Tissue-type plasminogen activator, Neuroprotection, Anesthetic agent, Magnetic resonance imaging

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

CHU CaenRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

tPA-placebo

tPA-ketamine

Arm Description

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).

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).

Outcomes

Primary Outcome Measures

Cerebral infarction growth on diffusion weighted magnetic resonance imaging between admission and day 1.

Secondary Outcome Measures

National Institute of Health Stroke Scale

Modified Rankin Scale

Infarction volume on diffusion weighted magnetic resonance imaging

T2-weighted Fluid Attenuated Inversion Recovery Imaging infarct volume

Symptomatic intracerebral hemorrhage and/or death

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).

Full Information

NCT ID

NCT02258204

First Posted

October 3, 2014

Last Updated

February 23, 2016

Sponsor

University Hospital, Caen

Collaborators

Société Française d'Anesthésie Réanimation, Fondation NRJ

1. Study Identification

Unique Protocol Identification Number

NCT02258204

Brief Title

Ketamine for Thrombolysis in Acute Ischemic Stroke

Acronym

KETA

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 Type

Interventional

2. Study Status

Record Verification Date

February 2016

Overall Recruitment Status

Unknown status

Study Start Date

March 2015 (undefined)

Primary Completion Date

December 2017 (Anticipated)

Study Completion Date

February 2018 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University Hospital, Caen

Collaborators

Société Française d'Anesthésie Réanimation, Fondation NRJ

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Stroke

Keywords

Cerebral Infarct, Thrombolysis, Tissue-type plasminogen activator, Neuroprotection, Anesthetic agent, Magnetic resonance imaging

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

tPA-placebo

Arm Type

Placebo Comparator

Arm Description

Arm Title

tPA-ketamine

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Ketamine

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Placebo

Primary Outcome Measure Information:

Title

Cerebral infarction growth on diffusion weighted magnetic resonance imaging between admission and day 1.

Time Frame

Day 1

Secondary Outcome Measure Information:

Title

National Institute of Health Stroke Scale

Time Frame

day 0, day 1, day 7 and day 90

Title

Modified Rankin Scale

Time Frame

day 90

Title

Infarction volume on diffusion weighted magnetic resonance imaging

Time Frame

day 1

Title

T2-weighted Fluid Attenuated Inversion Recovery Imaging infarct volume

Time Frame

day 90

Title

Symptomatic intracerebral hemorrhage and/or death

Time Frame

day 90

Title

Arterial patency

Description

Time Frame

day 0 (before and after thrombectomy) and day 1

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

85 Years

Accepts Healthy Volunteers

Eligibility 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.

Facility Information:

Facility Name

CHU Caen

City

Caen

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Emmanuel Touzé, MD PhD

Phone

+33231064624

touze-e@chu-caen.fr

12. IPD Sharing Statement

Citations:

PubMed Identifier

11135617

Citation

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.

Results Reference

background

PubMed Identifier

21817137

Citation

Gakuba 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.

Results Reference

background

Learn more about this trial

Ketamine for Thrombolysis in Acute Ischemic Stroke

We'll reach out to this number within 24 hrs