The purpose of this study is to examine the effects of delivering intra-arterial recombinant tissue plasminogen activator (rt-PA) and ultrasound to the site of the blood clot blocking blood flow to the brain of stroke patients.
The overall goal of Interventional Management of Stroke (IMS II) study is to refine thrombolytic therapy for patients with acute ischemic stroke who can be treated within three hours of stroke onset.
This multi-center, non-randomized pilot study will provide preliminary data about the benefits and risks of combined intravenous (IV) and intra-arterial (IA) recombinant tissue plasminogen activator (rtPA) and low-intensity ultrasound energy in ischemic stroke patients with baseline NIHSSS >/= 10 in whom intravenous treatment can be started within three hours of stroke onset. rt-PA is a thrombolytic, clot-dissolving drug.
The primary objectives for the study are to obtain reliable estimates of the effectiveness and safety of a treatment approach combining IV/IA rt-PA and ultrasound for stroke patients; and to determine if the estimated effectiveness of combined IV/IA rt-PA at 3 months—as compared to the 3 month outcome of placebo-treated patients in the NINDS rt-PA Stroke Trial—warrants proceeding to a large, phase III randomized trial.
- Tissue plasminogen activator (Activase®)Drug
Intervention Desc: Thrombolytic
- Recombinant tissue plasminogen activator Drug
Intervention Desc: Low-dose IV rt-PA (0.6 mg/kg) followed by delivery of additional IA rt-PA (up to 22 mg).
- Low-intensity ultrasound Procedure
Intervention Desc: Delivery of additional IA rt-PA (up to 22 mg) in the setting of low-energy ultrasound via the EKOS microinfusion catheter at the site of IA occlusion in acute ischemic stroke patients with large strokes (NIHSS >/= 10) treated within 3 hours of symptoms onset.
- Allocation: Non-Randomized
- Masking: Open Label
- Purpose: Treatment
- Endpoint: Safety/Efficacy Study
- Intervention: Single Group Assignment
All Patients will receive 0.6 mg/kg of IV t-PA followed as soon as possible by angiography. If a thrombus is demonstrated by angiography, the patient will then be administered IA t-PA within 5 hours of the symptom onset via microcatheter at the site of the thrombus at a dose of up to 22 mg over two hours. An NIH Stroke Scale Score will be performed in every patient at baseline, post intravenous t-PA, after completion of intra-arterial t-PA therapy, at 24 +/- 6 hours, at 5 days or at discharge from hospital, and 90 +/- 7 days after the stroke. In addition, a Modified Rankin Scale to indicate the patient’s functional status prior to the qualifying stroke (pre-event) will be obtained at baseline. A safety outcome telephone or follow-up visit will occur at 7 days. Functional outcome will also be assessed by the Barthel Index, the Modified Rankin Scale, the Glasgow Outcome Scale, and the EuroQol at three months.
|Type||Measure||Time Frame||Safety Issue|
|Primary||The combined IV/IA t-PA approach is as safe as IV t-PA in the NINDS t-PA Trial as measured by life threatening bleeding complications during the first 36 hours after completion of t-PA infusion.|
|Secondary||The combined IV/IA t-PA approach is more effective than placebo-treated patients in the NINDS Stroke Trial as measured by favorable outcome using the Rankin of 0 or 1 at 3 months.|
|Primary||Efficacy endpoint is a modified Rankin Score of 0 or 1 at 3 months|
|Primary||the primary angiographic outcome measure will be the rate of TIMI Grade 3 recanalization of the targeted occluded vessel at one hour after start of IA rt-PA plus ultrasound therapy.|
|Primary||Primary Safety Endpoint||36 hours after completion of rt-PA infusion||Yes|
|Primary||Primary Angiographic Outcome||60 minutes after start of IA therapy||No|
|Primary||Primary Outcome Measure||3 months following treatment||No|