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

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ClinicalTrials.gov Identifier: NCT02338466
Recruitment Status : Not yet recruiting
First Posted : January 14, 2015
Last Update Posted : September 23, 2016
Sponsor:
Information provided by (Responsible Party):
University Hospital Center of Martinique

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.


Condition or disease Intervention/treatment Phase
Nervous System Disorders Cerebral Artery Drug: rt-PA Drug: tenecteplase Phase 2

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  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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).
Study Start Date : November 2016
Estimated Primary Completion Date : December 2017
Estimated Study Completion Date : March 2018

Resource links provided by the National Library of Medicine


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 Name: 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 Name: 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 Name: Metalyse




Primary Outcome Measures :
  1. 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.




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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02338466


Contacts
Contact: Julien JOUX, MD +596 596 55 22 61 julien.joux@chu-fortdefrance.fr

Sponsors and Collaborators
University Hospital Center of Martinique
Investigators
Principal Investigator: Julien JOUX, MD Centre Hospitalier Universiatire de Martinique

Responsible Party: University Hospital Center of Martinique
ClinicalTrials.gov Identifier: NCT02338466     History of Changes
Other Study ID Numbers: 13/EC/02
First Posted: January 14, 2015    Key Record Dates
Last Update Posted: September 23, 2016
Last Verified: September 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Cerebral Arterial Diseases
Nervous System Diseases
Infarction, Middle Cerebral Artery
Cerebral Infarction
Brain Infarction
Brain Ischemia
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Intracranial Arterial Diseases
Stroke
Vascular Diseases
Cardiovascular Diseases
Tissue Plasminogen Activator
Tenecteplase
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action