A prospective, multicenter, randomized, controlled, open-label, blinded endpoint trial to evaluate the safety and efficacy of intravenous administration of tirofiban for preventing early neurological deterioration after intravenous thrombolysis in patients with acute ischemic stroke.
Intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA), administered within 4.5 hours of symptom onset, remains the standard treatment strategy for acute ischemic stroke. However, approximately 6-40% of patients experienced early neurological deterioration following intravenous thrombolysis, among which more than 70% resulted from ischemic events, with 20-34% due to early re-occlusion of the recanalized artery. Augmented platelet activation, triggered by the activated coagulation cascade and endothelial injury during rt-PA administration, is recognized as one of the primary reasons for ischemic events after intravenous thrombolysis. Early antiplatelet therapy following rt-PA effectively reduces neurological deterioration and improves functional outcomes. However, the current guidelines recommend that antiplatelet therapy should be initiated 24 hours after intravenous thrombolysis due to the potential risk of intracerebral hemorrhage. Tirofiban, a glycoprotein (GP) IIb/IIIa receptor inhibitor renowned for its rapid action, high selectivity, and short half-life, has been found to exert a remarkable antiplatelet effect by effectively blocking the terminal pathway that triggers platelet aggregation. One recent randomized trial found that among patients with acute non-cardioembolic ischemic stroke who presented within 24 hours of symptom onset, intravenous tirofiban resulted in a lower likelihood of early neurological deterioration than oral aspirin, without increasing the risk of intracranial hemorrhage or systematic bleeding. Another randomized trial found that treatment with intravenous tirofiban administration was safe and significantly improved 3-month functional outcomes in patients who experienced early neurological deterioration or no improvement within 24 hours of intravenous thrombolysis, compared with aspirin. Furthermore, our previous study found that early administration of tirofiban in patients with early neurological deterioration within the first 24 hours of intravenous thrombolysis did not increase the risk of symptomatic intracerebral hemorrhage, any intracerebral hemorrhage, or mortality. In contrast, it was associated with neurological improvement at 3 months. However, whether early administration of tirofiban can safely and effectively prevent neurological deterioration in patients with acute ischemic stroke treated with intravenous thrombolysis within 24 hours remains unclear, while the subset of patients who may benefit from early antiplatelet therapy.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
302
Tirofiban will use a loading dose, 0.4 μg/kg/min × 30 minutes, then 0.1μg/kg/min infusion until 24 hours after Intravenous thrombolytic therapy, or use a loading dose, 25 μg/kg, administrated within 3 minutes, then 0.15μg/kg/min infusion until 24 hours after Intravenous thrombolytic therapy.
Patients will receive standard antiplatelet therapy.
Xuanwu Hospital, Capital Medical University
Beijing, Beijing Municipality, China
Proportion of patients experiencing neurological deterioration within 24 hours after intravenous thrombolysis.
National Health Institute Stroke Scale (NIHSS): stroke symptom severity scale ranging from 0-42. A higher score means more severe stroke symptoms. Neurological deterioration is defined as an increase in NIHSS by ≥ 4 points compared to the lowest NIHSS.
Time frame: Within 24 hours after intravenous thombolysis.
Change of the NIHSS
National Health Institute Stroke Scale (NIHSS): stroke symptom severity scale with a range of 0-42. Higher score means more severe stroke symptoms.
Time frame: 7 days or discharge after intravenous thrombolytic therapy
The proportion of patients with a modified Rankin scale (mRS) score of 0-1 at 30-day follow up.
The mRS is an ordinal, graded interval scale that assigns patients among 7 global disability levels, which ranging from 0 (no symptom) to 5 (severe disability) and 6 (death).
Time frame: 30 days after stroke
The proportion of patients with a modified Rankin scale (mRS) score of 0-1 at 90-day follow up.
The mRS is an ordinal, graded interval scale that assigns patients among 7 global disability levels, which ranging from 0 (no symptom) to 5 (severe disability) and 6 (death).
Time frame: 90 days after stroke
The proportion of patients with a modified Rankin scale (mRS) score of 0-2 at 30-day follow up.
The mRS is an ordinal, graded interval scale that assigns patients among 7 global disability levels, which ranging from 0 (no symptom) to 5 (severe disability) and 6 (death).
Time frame: 30 days after stroke
The proportion of patients with a modified Rankin scale (mRS) score of 0-2 at 90-day follow up.
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The mRS is an ordinal, graded interval scale that assigns patients among 7 global disability levels, which ranging from 0 (no symptom) to 5 (severe disability) and 6 (death).
Time frame: 90 days after stroke
Distribution of modified Rankin Scale (mRS) scores at 90 day.
The mRS is an ordinal, graded interval scale that assigns patients among 7 global disability levels, which ranging from 0 (no symptom) to 5 (severe disability) and 6 (death).
Time frame: 90 days after stroke
Incidence of symptomatic intracranial hemorrhage within 24 hours of intervention.
Symptomatic intracranial hemorrhage is defined as the demonstration of hemorrhage within brain parenchyma on head imaging leading to an increase of at least 4 points in the NIHSS score, according to the criteria of the European Cooperative Acute Stroke Study III (ECASS III).
Time frame: Within 24 hours of intervention
Incidence of any intracranial hemorrhage within 24 hours of intervention.
Any intracranial hemorrhage is defined as the demonstration of hemorrhage within brain parenchyma on head imaging, according to the criteria of the ECASS III.
Time frame: Within 24 hours of intervention
Incidence of systemic hemorrhage within 90 days after stroke.
The incidence of systemic hemorrhage at any time from randomization through day 90, according to the criteria of the GUSTO.
Time frame: Within 90 days after stroke.
Incidence of recurrent stroke or other vascular events within 90 days after stroke.
The incidence of recurrent stroke or other vascular events (including hemorrhagic and ischemic stroke, myocardial infarction, and cardiovascular death) within 90 days of randomization.
Time frame: Within 90 days after stroke.
All-cause death within 90 days after stroke.
The incidence of death events at any time from randomization through day 90.
Time frame: Within 90 days after stroke.
Incidence of Adverse Events/Serious Adverse Events within 90 days after stroke.
The incidence of other adverse events and serious adverse events at any time from randomization through day 90.
Time frame: Within 90 days after stroke.
Proportion of patients experiencing neurological deterioration (an increase in NIHSS by ≥ 2 points compared to the lowest NIHSS) within 24 hours after intravenous thrombolysis.
National Health Institute Stroke Scale (NIHSS): stroke symptom severity scale with a range of 0-42. Higher score means more severe stroke symptoms.
Time frame: Within 24 hours of intravenous thrombolysis.
Proportion of patients experiencing neurological deterioration (an increase in NIHSS by ≥ 4 points compared to the lowest NIHSS) within 48 hours after intravenous thrombolysis.
National Health Institute Stroke Scale (NIHSS): stroke symptom severity scale with a range of 0-42. Higher score means more severe stroke symptoms.
Time frame: Within 48 hours after intravenous thrombolysis.
Proportion of patients experiencing (an increase in NIHSS by ≥ 4 points compared to the lowest NIHSS) within 72 hours after intravenous thrombolysis.
National Health Institute Stroke Scale (NIHSS): stroke symptom severity scale with a range of 0-42. Higher score means more severe stroke symptoms.
Time frame: Within 72 hours after intravenous thrombolysis.
Proportion of patients experiencing neurological deterioration (an increase in NIHSS by ≥ 4 points compared to the lowest NIHSS) within 7 days after intravenous thrombolysis.
National Health Institute Stroke Scale (NIHSS): stroke symptom severity scale with a range of 0-42. Higher score means more severe stroke symptoms.
Time frame: Within 7 days after intravenous thrombolysis.
Proportion of patients with a decrease in NIHSS by ≥ 2 points compared to NIHSS at randomization.
National Health Institute Stroke Scale (NIHSS): stroke symptom severity scale with a range of 0-42. Higher score means more severe stroke symptoms.
Time frame: 24 hours after intravenous thrombolysis.