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

June 19, 2018 updated by: University Hospital Center of Martinique

Randomized Therapeutic Study Assessing the Superiority of a Sequential Intravenous Thrombolysis Treatment (Rt-PA + Tenecteplase) in Comparison With Rt-PA Standard Treatment in Proximal Middle Cerebral Artery Occlusion (DIVA).

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.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

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).

Study Type

Interventional

Phase

  • Phase 2

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 85 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: 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.
Drug: 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.
Other Names:
  • Actilyse
Active Comparator: 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.
Drug: 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.
Other Names:
  • Actilyse
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).

Other Names:
  • Metalyse

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical outcome ill be assessed at 3-month with the modified Rankin score by a blinded examiner.
Time Frame: 3 months

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital Center of Martinique

Investigators

  • Principal Investigator: Julien JOUX, MD, Centre Hospitalier Universiatire de Martinique

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

July 1, 2016

Primary Completion (Anticipated)

July 1, 2018

Study Completion (Anticipated)

September 1, 2018

Study Registration Dates

First Submitted

January 12, 2015

First Submitted That Met QC Criteria

January 13, 2015

First Posted (Estimate)

January 14, 2015

Study Record Updates

Last Update Posted (Actual)

June 21, 2018

Last Update Submitted That Met QC Criteria

June 19, 2018

Last Verified

June 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 13/EC/02

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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