Superiority of Rt-PA + Tenecteplase in Comparison With Rt-PA Only in Proximal Middle Cerebral Artery Occlusion

NCT ID: NCT02338466

Last Updated: 2018-06-21

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-07-31
• Study Completion Date: 2018-09-30

Brief Summary

Proximal Middle Cerebral Artery (MCA) occlusions constitute the most severe stroke. Intra-venous thrombolysis with rt-PA within the first 4,5 hours is the only proven effective treatment. Prognosis is closely related to the recanalization rate that reaches only 30 to 50%. A new therapeutic strategy consisting in a sequential intravenous (IV) thrombolysis by rt-PA followed by 50UI/kg of IV tenecteplase (TNK) has been proposed in case of no recanalization after rt-PA. A case series of 13 consecutive patients treated by this association has been published in 2011. A high rate of recanalization without hemorrhagic transformation increase has been reported. However, efficiency and safety of this therapeutic have to be assessed in a randomized multi-centric study. Such a study is of great interest since interventional neuroradiology has not already shown superiority regarding IV rt-PA. Moreover interventional neuroradiologists specialists are only available in major hospital and an IV sequential strategy could provide an interesting alternative.

Main study objectives:

Main Clinical Objective:

Sequential thrombolysis should be associated with a significant better outcome at 3-month, assessed by the modified Rankin score (mRS).

Main Radiological Objective:

Sequential thrombolysis should be associated with a higher rate of recanalization (TIMI 2b/3) at 24-hour.

Detailed Description

This is a Phase 2, multi-center, national, randomized, biomedical study comparing two therapeutic strategies in ischemic stroke associated with proximal middle cerebral artery occlusion.

Patients will be included in two randomized arms and the new sequential treatment approach (rt-PA + tenecteplase) will be compared with the standard treatment (rt-PA alone).

Conditions

Nervous System Disorders; Cerebral Artery

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

rt-PA

Patients treated by thrombolysis with rt -PA within 4h30 of the onset of symptoms to a proximal middle cerebral artery occlusion visible on a MRI 1 are pre- included. A second MRI ( IRM2 ) is performed between 1 hour and 1.5 hours after administration of rt-PA in the usual way .

After the treatment by rt-PA, if there is no recanalization (TIMI score: 0,1, 2a), the patient is included. A patient included will be randomized either in the arm "rt-PA treatment only" or in the arm "rt-PA + tenecteplase treatment". If he is included in the arm "rt-PA only", he will not receive any other treatment for the study.

Group Type: PLACEBO_COMPARATOR

rt-PA

Intervention Type: DRUG

0,9 mg/kg of rt-PA is infused intravenously 60 minutes, with 10% of the total dose administered as an initial intravenous bolus.

rt-PA + tenecteplase

If patient is in the arm "rt-PA + tenecteplase", he will receive tenecteplase (50UI/Kg) treatment. A third MRI will be performed at 24hour that will assess the recanalization status (TIMI), the final volume infarct and the hemorrhagic complications.

Group Type: ACTIVE_COMPARATOR

rt-PA

Intervention Type: DRUG

0,9 mg/kg of rt-PA is infused intravenously 60 minutes, with 10% of the total dose administered as an initial intravenous bolus.

tenecteplase

Intervention Type: DRUG

Tenecteplase is under the form of powder and solvent for solution for injection.

The maximum duration of this treatment is 15 seconds by a single bolus intravenous injection (0, 25 mg/kg).

Interventions

rt-PA

0,9 mg/kg of rt-PA is infused intravenously 60 minutes, with 10% of the total dose administered as an initial intravenous bolus.

Intervention Type: DRUG

tenecteplase

Tenecteplase is under the form of powder and solvent for solution for injection.

The maximum duration of this treatment is 15 seconds by a single bolus intravenous injection (0, 25 mg/kg).

Intervention Type: DRUG

Other Intervention Names

Actilyse; Metalyse

Eligibility Criteria

Inclusion Criteria

• Age between 18 and 85 years
• Cerebral infarction in relation with a proximal middle cerebral artery occlusion (M1 ou M2)
• NIHSS between 4 and 23
• Patient treated with intravenous rt-PA (0,9 mg/kg) within the first 4.5 hours
• No recanalization on the MRI performed 1 hour after rt-PA initiation (TIMI 0,1 ou 2a)
• Administration of TNK within the first 6 hours
• Informed and written consent obtained from the patient or next of kin
• Patient insured under the French social security system

Exclusion Criteria

• Contraindication to MRI
• Contraindication to rt-PA administration
• Contraindication to TNK administration
• Contraindication to stroke thrombolysis
• Refusal to sign the informed consent
• Extensive small arteries disease (>5 microbleed and/or Fazekas score≥3)
• Systolic arterial pression> 185 mmHg or diastolic arterial pression > 110 mmHg
• Glycemia < 3 mmol/l (0,5g/l) or > 22 mmol/l (4g/l)
• Thrombopenia < 100 000/mm3 or INR > 1,5.
• Patients treated with new oral anticoagulant.
• Seizure as one of acute stroke symptoms
• Lumbar or arterial puncture in the previous 7 days or major surgery in the previous 15 days
• Carotid occlusion associated with MCA occlusion
• Thrombus length > 12mm assessed on gradient echo sequences
• Large DWI lesion, defined as ASPECTS < 7 / 10
• DWI/PWI Mismatch < 20% (when performed) on MRI 2
• Marked FLAIR hypersignal on cortical structure and light hypersignal on caudate or lenticular nucleus assessed on MRI 2.
• Parenchymal hemorrhage on MRI 2
• Pregnancy or breast feeding
• Patient currently included in a biomedical study

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital Center of Martinique

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Julien JOUX, MD

Role: PRINCIPAL_INVESTIGATOR

Centre Hospitalier Universiatire de Martinique

Other Identifiers

13/EC/02

Identifier Type: -

Identifier Source: org_study_id