Nervous System DisordersPhase 2DIVANCT02338466
Superiority of Rt-PA + Tenecteplase in Comparison With Rt-PA Only in Proximal Middle Cerebral Artery Occlusion
A Phase 2 study testing rt-PA and tenecteplase in people with Nervous System Disorders and Cerebral Artery, run by University Hospital Center of Martinique.
Trial 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%. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Nervous System Disorders, Cerebral Artery
- What is being tested?
- rt-PA and tenecteplase
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Jul 2016to Sep 2018
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
Show all 20Show fewer
- 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
About this study
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).
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:
Read more
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.
Read the 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).
- Conditions
- Nervous System Disorders, Cerebral Artery
- Being tested
- rt-PA, tenecteplase
- Medical subject headings
- Nervous System Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rt-PADrug
Also called Actilyse
0,9 mg/kg of rt-PA is infused intravenously 60 minutes, with 10% of the total dose administered as an initial intravenous bolus.
tenecteplaseDrug
Also called Metalyse
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).
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: rt-PA; Drug: tenecteplase |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jan 2015 (estimated)
- Study startJul 2016 (estimated)
- Primary completionJul 2018 (estimated)
- Study completionSep 2018 (estimated)
Why it stopped: Departure of the principal investigator and lack of succession
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Nervous System DisordersStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital Center of Martinique
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Julien JOUX, MD, Principal investigator, Centre Hospitalier Universiatire de Martinique
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02338466
- Sponsor's protocol ID
- 13/EC/02
- Acronym
- DIVA
- Status last verified
- Jun 2018
- First submitted
- 12 Jan 2015
- Last updated
- 21 Jun 2018
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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).
- ClinicalTrials.gov ID
- NCT02338466
- Acronym / sponsor ID
- DIVA / 13/EC/02
- Conditions
- Nervous System Disorders, Cerebral Artery
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Departure of the principal investigator and lack of succession
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University Hospital Center of MartiniqueUniversity, hospital or other
- Study start
- Jul 2016 (estimated)
- Primary completion
- Jul 2018 (estimated)
- Study completion
- Sep 2018 (estimated)
- First posted
- 14 Jan 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| rt-PA | Placebo comparator | Drug: rt-PAPatients 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. |
| rt-PA + tenecteplase | Active comparator | Drug: rt-PA, Drug: tenecteplaseIf 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. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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)
Key exclusion criteria (20 listed)
- Contraindication to MRI
- Contraindication to rt-PA administration
- Contraindication to TNK administration
- Contraindication to stroke thrombolysis
- Refusal to sign the informed consent
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| rt-PAAlso: Actilyse0,9 mg/kg of rt-PA is infused intravenously 60 minutes, with 10% of the total dose administered as an initial intravenous bolus. | Drug | rt-PA, rt-PA + tenecteplase |
| tenecteplaseAlso: MetalyseTenecteplase 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). | Drug | rt-PA + tenecteplase |
Primary outcome
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.
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jun 2018.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Julien JOUX, MD principal investigator
Centre Hospitalier Universiatire de Martinique
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing rt-PA and tenecteplase in people with Nervous System Disorders and Cerebral Artery, run by University Hospital Center of Martinique.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 21 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical outcome ill be assessed at 3-month with the modified Rankin score by a blinded examiner. (time frame: 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jun 2018.