DEFUSE Study
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Diffusion-weighted imaging Evaluation For Understanding Stroke Evolution
DEFUSE is a multicenter, open-label, pilot study of intravenous (IV) t-PA administered to selected stroke patients within 3-6 hours after symptom onset. The NIH is funding this trial.
We are investigating whether specific profiles on DWI and PWI predict a favorable clinical response to intravenous t-PA therapy administered between three and 6 hours after stroke onset.
We hypothesize that patient subgroups who are likely to benefit from thrombolytic therapy can be identified based on a combination of blood flow parameters and an assessment of the degree of early ischemic brain injury – variables for which the MRI techniques of DWI and PWI are extremely sensitive.
Check the inclusion and clinical exclusion criteria for the study. The criteria for enrollment are similar to the NINDS exclusion criteria. A notable difference is the requirement for a NIHSS of at least 6 and the longer time window. The dose of rt-PA used is 0.9mg/kg (max 90mg). Additional CT and MR criteria are described here. Early involvement of more than 1/3 of the MCA is an exclusion criterion.
Our CRF is web-based and can be accessed at www.dynarand.com (trial centers only).
Inclusion Criteria
- Age greater than 18 years.
- Clinical diagnosis of ischemic stroke causing measurable neurological deficits (NIHSS>5)
- Onset of symptoms of ischemic stroke within 3-6 hours of the time of treatment initiation.
- Patient must undergo both a baseline CT and MRI before t-PA administration.
Clinical Exclusion Criteria
- Coma or severe obtundation with fixed eye deviation and complete hemiplegia.
- NIHSS <6 or major symptoms that are rapidly improving by the time of enrollment.
- Stroke within the previous 6 weeks.
- Preexisting Modified Rankin Scale Score of 3 or higher.
- Seizure <6 hours prior to administration of study drug.
- History of ICH, SAH, AVM, aneurysm, or previously known intracranial neoplasm that, in the opinion of the investigator, is terminal, or would increase the risk of intracranial bleeding after administration of thrombolytic therapy, or may confound neurological assessment.
- Clinical presentation suggestive of subarachnoid hemorrhage, even if initial CT is normal.
- Hypertension: SBP > 185 mmHg; or DBP > 110 mmHg on repeated measures prior to study entry requiring aggressive (e.g., intravenous antihypertensive treatment by continuous infusion) treatment to reduce blood pressure to within these limits.
- Presumed septic embolus.
- AMI <30 days
- Biopsy <30 days of a parenchymal organ or surgery that would increase the risk of unmanageable (e.g., uncontrolled by local pressure) bleeding after administration of thrombolytic therapy.
- Trauma <30 days, with internal injuries or ulcerative wounds.
- Any active or recent (within 30 days) hemorrhage that, in the opinion of the investigator, would increase the risk of unmanageable (e.g., uncontrolled by local pressure) bleeding after administration of thrombolytic therapy.
- Known hereditary or acquired hemorrhagic diathesis
- Pregnancy, lactation, or parturition within the previous 30 days.
- Glucose < 50 or > 400 mg/dL, platelets <100,000/mm3, Hct < 25.
- Other serious, advanced, or terminal illness.
- Any other condition that the investigator feels would pose a significant hazard to the patient if intravenous t-PA were initiated.
- Current participation in another research drug treatment protocol
CT Exclusion Criteria
- Evidence of acute or chronic intracranial bleeding.
- Likely etiology other than acute brain ischemia.
- Early infarct signs greater than 1/3 of the MCA territory.
MR Exclusion Criteria
- Evidence of acute or chronic intracranial bleeding.
- Likely etiology other than acute brain ischemia.
- Unable to undergo MRI
Frequently Asked Questions
- When does the second MR have to be performed ?
- Can I start tPA during the perfusion scan ?
- Can I fill out the CRF directly online ?
- Where can I find workbooks ?
- Why not use only MRA as most patients with a stenosis or occlusion will have a mismatch ?
When does the second MR have to be performed?
The second MR should be performed between 3 to 6 hours after t-PA bolus
Can I start tPA during the perfusion scan?
The perfusion scan takes only 80 seconds. We want all MR sequences to be finished before the tPA bolus. Preliminary data suggest that recanalisation can occur very rapidly after tPA infusion.
Can I fill out the CRF directly online?
The CRF can, at present, not be filled out online immediately, as there is no simple way to correct data once they have been submitted. Workbooks are available to enter the data. The first page, Enrollment, which contains demographic information should however be entered at enrollment. The Data Management Center is immediately notified with an e-mail when a new patient is entered and is notified of Serious Adverse Events
Workbooks are available by sending an e-mail to Stephanie Kemp .
Why not use MRA alone as most patients with a stenosis or occlusion will have a mismatch?
We have encountered patients with a mismatch who do not have stenosis or occlusion on MRA. These patients might have lesions below the resolution of MRA or have a 'no reflow' situation. Perfusion MR should be performed on all patients.
