Ketamine for Thrombolysis in Acute Ischemic Stroke

NCT02258204 | Unknown Phase 1 DMC

• 1 other identifier: KETA
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

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.

Conditions

Stroke

Keywords

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

Outcome Measures

Primary Outcomes (1)

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

  Day 1

Secondary Outcomes (6)

• National Institute of Health Stroke Scale

  day 0, day 1, day 7 and day 90

• Modified Rankin Scale

  day 90

• Infarction volume on diffusion weighted magnetic resonance imaging

  day 1

• T2-weighted Fluid Attenuated Inversion Recovery Imaging infarct volume

  day 90

• Symptomatic intracerebral hemorrhage and/or death

  day 90

Study Arms (2)

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).

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).

Drug: Ketamine

Interventions

Ketamine DRUG

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

tPA-ketamine

Placebo DRUG

tPA-placebo

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University Hospital, Caen: lead
• Société Française d'Anesthésie Réanimation: collaborator
• Fondation NRJ: collaborator

Study Sites (1)

CHU Caen

Caen, France

RECRUITING

Related Publications (2)

• 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.

  PMID: 11135617 BACKGROUND

• 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.

  PMID: 21817137 BACKGROUND

MeSH Terms

Conditions

Stroke; Cerebral Infarction

Interventions

Ketamine

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Brain Infarction; Brain Ischemia; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: October 3, 2014
• First Posted: October 7, 2014
• Study Start: March 1, 2015
• Primary Completion: December 1, 2017
• Study Completion: February 1, 2018
• Last Updated: February 24, 2016

Record last verified: 2016-02

Locations

FR (1)