Ketamine for Thrombolysis in Acute Ischemic Stroke
- Registration Number
- NCT02258204
- Lead Sponsor
- 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.
- 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.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 50
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description tPA-placebo 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). tPA-ketamine 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).
- Primary Outcome Measures
Name Time Method Cerebral infarction growth on diffusion weighted magnetic resonance imaging between admission and day 1. Day 1
- Secondary Outcome Measures
Name Time Method 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 Arterial patency 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).
Trial Locations
- Locations (1)
CHU Caen
🇫🇷Caen, France