Study of Aspirin and TPA in Acute Ischemic Stroke
Recruitment status was Not yet recruiting
This study will determine the safety of 500mg of aspirin added to IV TPA at standard doses to prevent re-occlusion of cerebral vessels after successful reperfusion. In ischemic stroke brain arteries are occluded either by an embolus originating in the heart or large vessels leading to the brain or by a process of acute thrombosis of the cerebral arteries over a ruptured atherosclerotic plaque. Rupture of the plaque exposes thrombogenic elements within the plaque and leads to accumulation and activation of platelets and induction of the clotting cascade eventually leading to acute thrombosis and occlusion of the artery. TPA is currently approved by the Food and Drug Administration to treat heart and brain problems caused by blockage of arteries. It activates plasminogen and leads to disintegration of the thrombus/embolus. It is effective only if begun within 3 to 4.5 hours of onset of the stroke because of potential deleterious side effects including life threatening symptomatic intracranial hemorrhage (sICH) when the drug is administered outside of this time window.
Reperfusion of the ischemic brain (i.e. timely opening of the occluded artery) with TPA is associated with improved outcome. However, in about 33% of patients that have successfully reperfused after TPA the artery re-occludes within the first few hours resulting in worsening neurological symptoms and worse functional outcome. This re-occlusion is speculated to result from re-thrombosis over an existing ruptured atherosclerotic plaque. This is explained by the relatively short half life of TPA leaving the exposed ruptured plaque intact which leads to re-activation of platelets and clotting factors and re-thrombosis. Thus, we hypothesize that the addition of an antiplatelet agent to TPA would result in lower rates of re-occlusion after AIS. The FDA approved TPA for patients with AIS but discouraged the concomitant use of anti-platelet or anti-thrombotic drugs for the first 24hours after administration of TPA because of concerns that such therapy may result in increased rates of intracerebral hemorrhage. Aspirin is a well known platelet anti-aggregant that works by inhibition of cycloxygenase 1 and reduction in thromboxane A levels. It has a rapid onset of action and additional potential beneficial anti-inflammatory effects in patients with AIS. The international stroke study showed that acute treatment of stroke patients with 500mg of aspirin is safe and feasible and results in better outcome. Furthermore, the drug was safe in these circumstances with an ICH rate of only .
Therefore, the purpose of this clinical trial is to examine the safety and efficacy of the combination of aspirin with rt-TPA in patients with AIS.
Patients between 18 and 80 years of age who have had a mild or moderate acute stroke involving the middle cerebral artery territory up to 4.5 hours before starting study drugs may be eligible for this study. Candidates will be screened with a medical history and physical examination, blood tests, rating of neurological deficits such as cognition deficits or problems walking that resulted from the stroke, and a computed tomography (CT) or a magnetic resonance (MRI) scan of the head. CT involves the use of specialized X-rays and MRI involves a magnetic field to obtain images of the brain. The patient lies on a table that is moved into a cylindrical machine (the scanner) for the imaging study, which usually takes about 5 to 10 minutes.
All participants will receive 0.9mg/kg of TPA. The drug is infused into the vein over 1hour with 10% of the total dose given as a bolus. Half of the patients will also receive 500mg of aspirin (one tablet P.O) which may reduce the likelihood of arterial re-occlusion. And possibly also increase the effectiveness of TPA in opening the blocked blood vessel. Patients will be monitored daily until discharge from the hospital, or until day 5, whichever is earlier. Assessments will include physical examinations, blood tests to examine factors involved in blood clotting, and transcranial Doppler (TCD) to evaluate the patency rate achieved after treatment. MRI or CT scans will be performed at 5 days (or sooner as needed) to evaluate both the response to treatment and drug side effects. Patients will return for a follow-up examination and MRI/CT scan 30 days after treatment.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase 1 Study to Assess the Safety of 500mg of Aspirin Added to IV TPA at Standard Doses to Prevent re-Occlusion of Cerebral Vessels After Successful Reperfusion.|
- PRIMARY ENDPOINT
- Safety (mortality, symptomatic ICH, asymptomatic ICH).
- Proportion of patients achieving excellent functional outcome as determined by a modified Rankin score (mRS) < 2 and Barthel index (BI) > 85 obtained at 3 months after stroke onset.
- Good neurological outcome as assessed by NIH stroke scale score at discharge < 5 or showing improvement of at least 8 points from the initial stroke score.
- Good neurological outcome as assessed by NIH stroke scale score at 3 months < 5 or showing improvement of at least 8 points from the initial stroke score.
|Study Start Date:||March 2007|
|Estimated Study Completion Date:||December 2012|
Please refer to this study by its ClinicalTrials.gov identifier: NCT00417898
|Contact: Ronen R Leker, MDemail@example.com|
|Contact: Tamir Ben Hur, MD, PhDfirstname.lastname@example.org|
|Hadassah University Medical Center||Not yet recruiting|
|Jerusalem, Israel, 91120|
|Contact: Arik Tzukert, DMD : 00 972 2 6776095 email@example.com|
|Contact: Hadas Lemberg, PhD : 00 972 2 6777572 firstname.lastname@example.org|
|Principal Investigator:||Ronen R Leker, MD||Hadassah Medical Organization|