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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Recruitment Status : Withdrawn (Departure of the principal investigator and lack of succession)
First Posted : January 14, 2015
Last Update Posted : June 21, 2018
Sponsor:
Information provided by (Responsible Party):
University Hospital Center of Martinique

Tracking Information
First Submitted Date  ICMJE January 12, 2015
First Posted Date  ICMJE January 14, 2015
Last Update Posted Date June 21, 2018
Estimated Study Start Date  ICMJE July 2016
Estimated Primary Completion Date July 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 13, 2015)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02338466 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Superiority of Rt-PA + Tenecteplase in Comparison With Rt-PA Only in Proximal Middle Cerebral Artery Occlusion
Official Title  ICMJE 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).
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).

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Nervous System Disorders
  • Cerebral Artery
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • 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.

    Intervention: Drug: rt-PA
  • 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.
    Interventions:
    • Drug: rt-PA
    • Drug: tenecteplase
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Withdrawn
Actual Enrollment  ICMJE
 (submitted: June 19, 2018)
0
Original Estimated Enrollment  ICMJE
 (submitted: January 13, 2015)
60
Estimated Study Completion Date  ICMJE September 2018
Estimated Primary Completion Date July 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 85 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02338466
Other Study ID Numbers  ICMJE 13/EC/02
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party University Hospital Center of Martinique
Study Sponsor  ICMJE University Hospital Center of Martinique
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Julien JOUX, MD Centre Hospitalier Universiatire de Martinique
PRS Account University Hospital Center of Martinique
Verification Date June 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP