A Multicenter, Three-Arm, Open-Label, Endpoint-Blinded Randomized Controlled Trial to Evaluate the Optimal Duration of Early Tirofiban After Intravenous Thrombolysis in Acute Ischemic Stroke (INSTANT-2)
A Multicenter, Three-Arm, Open-Label, Endpoint-Blinded Randomized Controlled Trial to Evaluate the Optimal Infusion Duration of Early Tirofiban Treatment After Intravenous Thrombolysis in Patients With Acute Ischemic Stroke (INSTANT-2)
Acute ischemic stroke is a leading cause of disability and mortality among dults in China. Although intravenous thrombolysis serves as first-line reperfusion therapy, nearly half of patients fail to achieve vascular recanalization. The reocclusion rate ranges from 14% to 34%, and many patients are left with residual neurological deficits. Early antiplatelet therapy initiated after thrombolysis may sustain persistent reperfusion and improve prognosis. However, current guidelines generally recommend delaying antiplatelet treatment until 24 hours post-thrombolysis due to bleeding risks, and direct evidence for the optimal initiation timing remains lacking. Tirofiban is a rapidly acting, short-half-life, reversible glycoprotein IIb/IIIa receptor antagonist. Previous studies indicate its potential benefits and acceptable safety when administered after intravenous thrombolysis.
This is a multicenter, three-arm, open-label, endpoint-blinded randomized controlled trial. A total of 1482 non-cardioembolic patients without large or medium vessel occlusion and with residual neurological deficits (NIHSS ≥4) after thrombolysis will be enrolled. Participants will be randomly allocated to the tirofiban 24-hour group, tirofiban 48-hour group, or blank control group. The primary outcome is the proportion of patients with excellent functional outcome defined as modified Rankin Scale (mRS) score 0-1 at 90 days. Symptomatic intracranial hemorrhage and neurological outcomes will also be evaluated. The study aims to determine the optimal duration of tirofiban treatment after thrombolysis and provide high-level evidence for precise interventions in the acute phase of stroke.
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Tipo de estudio
Inscripción (Estimado)
Fase
- Fase 2
- Fase 3
Contactos y Ubicaciones
Estudio Contacto
- Nombre: Guoyong Zeng, doctor
- Número de teléfono: +8613507079530
- Correo electrónico: hsyygy@126.com
Copia de seguridad de contactos de estudio
- Nombre: Fan Zhang, doctor
- Número de teléfono: +8618970148470
- Correo electrónico: zhappy0066@126.com
Ubicaciones de estudio
-
-
Anhui
-
Fuyang, Anhui, Porcelana, 236600
- Taihe County People's Hospital
-
-
Fujian
-
Longyan, Fujian, Porcelana, 364000
- Longyan First Hospital of Fujian Medical University
-
-
Hunan
-
Xiangtan, Hunan, Porcelana, 411100
- Xiangtan Central Hospital (The Affiliated Hospital of Hunan University)
-
-
Jiangxi
-
Ganzhou, Jiangxi, Porcelana, 341000
- Ganzhou People's Hospital
-
Ganzhou, Jiangxi, Porcelana, 342414
- Xingguo People's Hospital, Xinguo Hospital of Gannan Medical University
-
Jingdezhen, Jiangxi, Porcelana, 333000
- Jingdezhen First People's Hospital
-
Jingdezhen, Jiangxi, Porcelana, 341000
- The First People's Hospital of Jingdezhen City
-
Jiujiang, Jiangxi, Porcelana
- Jiujiang First People's Hospital
-
-
Liaoning
-
Dalian, Liaoning, Porcelana, 116000
- Dalian Central Hospital
-
-
Sichuan
-
Mianyang, Sichuan, Porcelana, 621000
- The First People's Hospital of Mianyang (Mianyang 404 Hospital)
-
-
Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Inclusion Criteria:
- Age ≥ 18 years.
- Diagnosis of acute ischemic stroke meeting the diagnostic criteria from Chinese Guidelines for the Diagnosis and Treatment of Acute Ischemic Stroke 2023, and the patient has received intravenous thrombolysis with tenecteplase, alteplase or reteplase.
- Disabling stroke remains at 2-24 hours after completion of intravenous thrombolysis. Disabling stroke is defined as NIHSS score ≥ 4, or single limb motor subscore ≥ 2.
- Written informed consent is obtained from the patient or legal representative.
Exclusion Criteria:
- Intracranial hemorrhage confirmed by CT or MRI after intravenous thrombolysis and prior to randomization.
- CTA/MRA/DSA demonstrates occlusion of the internal carotid artery, M1 or M2 segment of the middle cerebral artery, anterior cerebral artery, or vertebrobasilar artery.
- History of atrial fibrillation or suspected cardioembolic stroke. Platelet count <100×10⁹/L on routine blood test.
- Renal insufficiency with estimated glomerular filtration rate (eGFR) <30 mL/min.
- Pregnant or breastfeeding women.
- Pre-existing neurological or psychiatric disorders that interfere with neurological function assessment.
- History of bleeding disorders, severe cardiac, hepatic or renal disease, or sepsis.
- Brain tumor with mass effect on imaging (excluding small meningioma). Intracranial aneurysm or arteriovenous malformation (AVM).
- Advanced illness with life expectancy less than 6 months.
- Current participation in another clinical trial.
- Other conditions deemed unsuitable for enrollment by the investigator.
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Doble
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
|
Experimental: Arm A: Tirofiban 24-hour group
Arm A: Patients receive tirofiban for 24 hours after intravenous thrombolysis. |
Intravenous infusion of tirofiban will be initiated after intravenous thrombolysis and continued for 24 hours. The dosage regimen follows the trial protocol. Intravenous infusion of tirofiban will be initiated after intravenous thrombolysis and continued for 48 hours. The dosage regimen follows the trial protocol. |
|
Experimental: Arm B: Tirofiban 48-hour group
Arm B: Patients receive tirofiban for 48 hours after intravenous thrombolysis. |
Intravenous infusion of tirofiban will be initiated after intravenous thrombolysis and continued for 24 hours. The dosage regimen follows the trial protocol. Intravenous infusion of tirofiban will be initiated after intravenous thrombolysis and continued for 48 hours. The dosage regimen follows the trial protocol. |
|
Comparador activo: Arm C: Standard care control group
No tirofiban is administered after intravenous thrombolysis. |
No tirofiban will be administered after intravenous thrombolysis. Patients receive routine standard clinical management according to hospital guidelines. |
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Proportion of patients with mRS 0-1 at 90 days
Periodo de tiempo: 90 days after randomization
|
Percentage of participants achieving modified Rankin Scale (mRS) score 0 or 1 at 90 days after randomization. |
90 days after randomization
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
mRS score at 90 days
Periodo de tiempo: 90 days after randomization
|
Modified Rankin Scale (mRS) score assessed at 90 days after randomization. |
90 days after randomization
|
|
EQ-5D-5L score at 90 days
Periodo de tiempo: 90 days after randomization
|
EQ-5D-5L questionnaire score assessed at 90 days after randomization. |
90 days after randomization
|
|
Proportion of patients with mRS 0-2 at 90 days
Periodo de tiempo: 90 days after randomization
|
Percentage of participants achieving modified Rankin Scale (mRS) score 0 to 2 at 90 days after randomization. |
90 days after randomization
|
|
Proportion of patients with mRS 0-3 at 90 days
Periodo de tiempo: 90 days after randomization
|
Percentage of participants achieving modified Rankin Scale (mRS) score 0 to 3 at 90 days after randomization. |
90 days after randomization
|
|
Proportion of early neurological improvement
Periodo de tiempo: 48 hours after randomization
|
Percentage of participants with early neurological improvement, defined as ≥30% reduction in NIHSS score at 48 hours post-randomization compared with the NIHSS score at randomization. |
48 hours after randomization
|
Otras medidas de resultado
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Incidence of symptomatic intracranial hemorrhage (sICH) within 48 hours
Periodo de tiempo: Within 48 hours after randomization
|
Proportion of participants with symptomatic intracranial hemorrhage (sICH) within 48 hours after randomization, defined by the Heidelberg criteria. |
Within 48 hours after randomization
|
|
Incidence of any intracranial hemorrhage (any ICH) within 48 hours
Periodo de tiempo: Within 48 hours after randomization
|
Proportion of participants with any intracranial hemorrhage (any ICH) within 48 hours after randomization. |
Within 48 hours after randomization
|
|
90-day mortality
Periodo de tiempo: 90 days after randomization
|
Proportion of participants who die within 90 days after randomization. |
90 days after randomization
|
Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Investigador principal: zhongming qiu, Xinqiao Hospital of the Army Medical University
Publicaciones y enlaces útiles
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Estimado)
Finalización primaria (Estimado)
Finalización del estudio (Estimado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
- Trastornos cerebrovasculares
- Enfermedades Cerebrales
- Enfermedades del Sistema Nervioso Central
- Enfermedades del Sistema Nervioso
- Enfermedades Vasculares
- Enfermedades cardiovasculares
- Carrera
- Accidente cerebrovascular isquémico
- Aminoácidos, péptidos y proteínas
- Aminoácidos
- Aminoácidos, aromáticos
- Aminoácidos, cíclico
- Tirosina
- Tirofibán
Otros números de identificación del estudio
- INSTANT-2
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Descripción del plan IPD
De-identified cleaned individual participant data (IPD) will be shared upon reasonable request after publication of the primary study results. All personal identifiers will be removed to protect participant privacy.
Marco de tiempo para compartir IPD
Available starting 6 months after publication of the primary manuscript.
Criterios de acceso compartido de IPD
Interested researchers may submit a formal research proposal and data access request to the corresponding author. The study steering committee will review each application.
Tipo de información de apoyo para compartir IPD
- PROTOCOLO DE ESTUDIO
- SAVIA
- CIF
- CÓDIGO_ANALÍTICO
- RSC
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .