Is the combination of low doses of argatroban in combination with rt-PA safe, and does it increase recanalization in patients with acute ischemic stroke.
All patients with acute ischemic stroke who qualify for IV rt-PA under accepted guidelines, and who have an occluded middle cerebral artery documented on TCD, receive standard dose IV rt-PA and a bolus and 48 hour infusion of argatroban aimed at prolonging the aPTT 1.75 X baseline. Follow up CT scanning and TCD every 30 minutes for 2 hours and then daily will determine the incidence of hemorrhage, recanalization and reocclusion, and serial neurological exam will determine the clinical outcome. For patients without temporal windows, a baseline CT-Angiogram (CTA) demonstrating arterial occlusion can also be enrolled. In those patients, a follow-up CTA (24-36 hours) will be performed.
- Tissue plasminogen activator (Activase®)Drug
Intervention Desc: Thrombolytic
- Argatroban (Novastan®)Drug
Intervention Desc: Argatroban IV Infusion at 1mcg/kg/min for 48 hours. ARM 1: Kind: Experimental Label: Intervention Description: Argatroban IV Infusion 1 mcg/kg/min for 48 hours
- Allocation: Non-Randomized
- Masking: Open Label
- Purpose: Treatment
- Endpoint: Safety/Efficacy Study
- Intervention: Single Group Assignment
All patients received the standard rtPA dose of 0.9 mg/kg, with 10% of the total dose given in 1 minute and the remainder infused across 60 minutes. Argatroban was administered intravenously within 1 hour of standard rtPA treatment initiation as an initial 100-?g/kg bolus in 3 to 5 minutes, followed by a continuous infusion of 1.0 ?g/kg per minute for 48 hours adjusted to a target partial thromboplastin time (aPTT) of 1.75 times that of the control group (baseline (±10%).
|Type||Measure||Time Frame||Safety Issue|
|Primary||Incidence of intracerebral hemorrhage.|
|Secondary||Complete recanalization at 2 hours.|
|Primary||Symptomatic and radiographic intracerebral hemorrhage||Within 7 days of enrollment||Yes|
|Secondary||arterial recanalization||Within 48 hours of treatment||No|
|Secondary||Arterial Complete Recanalization at 2 Hours Post tPA Bolus||2 hours complete recanalization post tPA bolus||No|
|Secondary||Arterial Complete Recanalization at 24 Hours Post tPA Bolus||24 hours from tPA bolus||No|