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

• Status: Withdrawn
• Trial end date: 2018-09-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University Hospital Center of Martinique
• Treatments: Tenecteplase; Tissue Plasminogen Activator

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