Acute Ischemic Stroke
Conditions
Keywords
randomized trial, tenecteplase, tirofiban, intravenous thrombolysis
Brief summary
The purpose of this study is to assess the safety and efficacy of early administration of tirofiban in patients treated with tenecteplase for acute ischemic stroke.
Detailed description
Intravenous thrombolysis with alteplase is recommended in treatment guidelines for patients with acute ischemic stroke. Previous studies showed that intravenous tenecteplase (0.25 mg/kg) is a reasonable alternative to alteplase for all patients presenting with acute ischemic stroke who meet standard criteria for thrombolysis. After thrombolysis-induced recanalisation, reocclusion occurs in 14-34% of patients, probably because of platelet activation. Early administration of antiplatelet therapy after intravenous thrombolysis could reduce the risk of reocclusion and improve outcome. The purpose of this study is to assess the safety and efficacy of early administration of tirofiban in patients treated with tenecteplase for acute ischemic stroke.
Interventions
Patients will receive a continuous intravenous infusion of tirofiban at a dose of 0.3 μg per kilogram of body weight per minute for 30 minutes, followed by a continuous infusion of 0.075 μg per kilogram per minute for 47.5h after start of tenecteplase treatment within 4-24 hours. Aspirin placebo (1 tablet) and/or clopidogrel placebo (1 tablet) will be given orally at 24h after intravenous tenecteplase. Antiplatelet therapy with aspirin (100 mg) and/or clopidogrel (75 mg) will be administered at 44h after randomization until the follow-up period of 90 days.
DRUGPlacebo
Patients will receive a continuous intravenous infusion of placebo at a dose of 0.3 μg per kilogram of body weight per minute for 30 minutes, followed by a continuous infusion of 0.075 μg per kilogram per minute for 47.5h after start of tenecteplase treatment within 4-24 hours. Aspirin (1 tablet) and/or clopidogrel (1 tablet) will be given orally at 24h after intravenous tenecteplase. Antiplatelet therapy with aspirin (100 mg) and/or clopidogrel (75 mg) will be administered at 44h after randomization until the follow-up period of 90 days.
Sponsors
Ganzhou People's Hospital
Second Affiliated Hospital of Guangxi Medical University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥ 18 years old; 2. Within 4-24 hours after intravenous thrombolytic therapy with tenerplase for acute ischemic stroke, there was no significant change in symptoms compared to the baseline (defined as an increase or decrease of 0 or 1 point in the NIHSS score), and neurological function deteriorated (defined as an increase of ≥ 2 in the NIHSS score compared to the baseline) Fluctuations in neurological function (defined as an increase of 4 points or more in the NIHSS score compared to the baseline and then a decrease of 4 points or more); 3. NIHSS ≥ 4 points before randomization; 4. The patient or their family members sign a written informed consent form.
Exclusion criteria
1. Intracranial hemorrhage was confirmed by CT or MRI after intravenous thrombolysis and before randomization; 2. CTA/MRA/DSA showed occlusion of the internal carotid artery, middle cerebral artery M1, M2 or M3 segment, anterior cerebral artery A1, A2 or A3 segment, posterior cerebral artery P1, P2 or P3, vertebral or basilar artery; 3. Confirmed or suspected cardioembolic stroke mechanisms, including any of the following: documented cardiac sources of thromboembolism: chronic or paroxysmal atrial fibrillation, rheumatic mitral stenosis, prosthetic heart valves, infective endocarditis, intracardiac thrombus or implanted prosthetic material, dilated cardiomyopathy (left ventricular ejection fraction \<40%), or spontaneous echo contrast in the left atrium; other laboratory-confirmed embolic sources: patent foramen ovale with concomitant atrial septal aneurysm, or cryptogenic stroke with a CHADS-VASC score ≥ 2 indicating high thromboembolic risk; 4. Blood platelet count was lower than 100×10\^9/L; 5. Renal insufficiency, glomerular filtration rate \< 30 mL/min; 6. Pregnant or lactating women; 7. Allergic to tirofiban, nickel, titanium or their alloys; 8. Prior neurological or psychiatric illness that prevents assessment of neurological function; 9. Pre-existing bleeding disease, severe heart, liver, or kidney disease, or sepsis; 10. Brain tumors with a space-occupying effect on imaging (other than micromeningiomas); 11. Intracranial aneurysm, arteriovenous malformation; 12. Life expectancy of any advanced disease \< 6 months; 13. Participating in other clinical trials.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Excellent functional outcome | 90 days post-randomization | modified Rankin scale score of 0 to 1. modified Rankin scale scores range from 0 to 6, with 0 indicating no disability, 1 no clinically significant disability, 2 slight disability, 3 moderate disability but able to walk unassisted, 4 moderately severe disability, 5 severe disability, and 6 death. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Early neurologic improvement | 48 hours post-randomization | defined as the National Institutes of Health Stroke Scale score at 48 hours after randomization, is reduced by 30% or more compared to the National Institutes of Health Stroke Scale score at randomization |
| Radiologic intracranial hemorrhage rate | 48 hours post-randomization | diagnosed with intracranial hemorrhage (including bleeding in brain parenchyma, subarachnoid space, etc.) via radiologic examinations (e.g., computed tomography or magnetic resonance imaging |
| Mortality | 90 days post-randomization | The proportion of participants who die from any cause within 90 days after randomization in the study |
| Incidence of non-hemorrhagic serious adverse events | Within 90 days post-randomization | such as pneumonia, respiratory failure, circulatory failure, cerebral herniation, secondary epilepsy, sepsis, renal failure, acute coronary syndrome, venous thrombosis, etc |
| Other serious adverse events | Within 90 days post-randomization | Serious adverse events that are not categorized as non-hemorrhagic (as listed in Outcome 10), including any unlisted severe medical events requiring medical intervention or leading to significant clinical deterioration |
| Ordinal degree of disability | 90 days post-randomization | Ordinal degree of disability on the modified Rankin scale score at 90 days (shift analysis) |
| Functionally independent | 90 days post-randomization | modified Rankin scale score of 0 to 2 |
| Ambulatory or bodily needs capable or better | 90 days post-randomization | modified Rankin scale score of 0 to 3 |
| Health-related quality of life | 90 days post-randomization | assessed with the European Quality Five Dimensions Five Level scale |
| Symptomatic intracranial hemorrhage | 48 hours post-randomization | defined as per the Heidelberg bleeding classification |
Other
| Measure | Time frame | Description |
|---|---|---|
| Functionally independent | 1 year post-randomization | modified Rankin scale score 0 to 2 at 1 year |
| Ambulatory or bodily needs capable or better | 1 year post-randomization | modified Rankin scale score 0 to 3 at 1 year |
| Excellent functional status | 1 year post-randomization | modified Rankin scale score 0 to 1 at 1 year |
| Ordinal degree of disability | 1 year post-randomization | Ordinal degree of disability on the modified Rankin scale score at 1 year (shift analysis) |
Countries
China
Contacts
Primary ContactDeyan Kong, MD
Backup ContactGuoyong Zeng, MD
Outcome results
None listed