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

NCT02338466 | Withdrawn Phase 2

• 1 other identifier: 13/EC/02
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Nervous System Disorders; Cerebral Artery

Outcome Measures

Primary Outcomes (1)

• Clinical outcome ill be assessed at 3-month with the modified Rankin score by a blinded examiner.

  The clinical outcome will be assessed at 3-month with the modified Rankin score by a blinded examiner. A score of 0-2 is considered good prognosis and a score 3-6 define a poor prognosis.

  3 months

Study Arms (2)

rt-PA

PLACEBO COMPARATOR

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.

Drug: rt-PA

rt-PA + tenecteplase

ACTIVE COMPARATOR

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.

Drug: rt-PA; Drug: tenecteplase

Interventions

rt-PA 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.

Also known as: Actilyse

rt-PA; rt-PA + tenecteplase

tenecteplase 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).

Also known as: Metalyse

rt-PA + tenecteplase

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital Center of Martinique: lead

MeSH Terms

Conditions

Nervous System Diseases

Interventions

Tissue Plasminogen Activator; Tenecteplase

Intervention Hierarchy (Ancestors)

Serine Endopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Serine Proteases; Plasminogen Activators; Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Biological Factors

Study Officials

• Julien JOUX, MD

  Centre Hospitalier Universiatire de Martinique

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 12, 2015
• First Posted: January 14, 2015
• Study Start: July 1, 2016
• Primary Completion: July 1, 2018
• Study Completion: September 1, 2018
• Last Updated: June 21, 2018

Record last verified: 2018-06

Data Sharing

• IPD Sharing: Will not share