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.
Studieoversikt
Status
Forhold
Intervensjon / Behandling
Studietype
Registrering (Antatt)
Fase
- Fase 2
- Fase 3
Kontakter og plasseringer
Studiekontakt
- Navn: Guoyong Zeng, doctor
- Telefonnummer: +8613507079530
- E-post: hsyygy@126.com
Studer Kontakt Backup
- Navn: Fan Zhang, doctor
- Telefonnummer: +8618970148470
- E-post: zhappy0066@126.com
Studiesteder
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Anhui
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Fuyang, Anhui, Kina, 236600
- Taihe County People's Hospital
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Fujian
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Longyan, Fujian, Kina, 364000
- Longyan First Hospital of Fujian Medical University
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Hunan
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Xiangtan, Hunan, Kina, 411100
- Xiangtan Central Hospital (The Affiliated Hospital of Hunan University)
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Jiangxi
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Ganzhou, Jiangxi, Kina, 341000
- Ganzhou People's Hospital
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Ganzhou, Jiangxi, Kina, 342414
- Xingguo People's Hospital, Xinguo Hospital of Gannan Medical University
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Jingdezhen, Jiangxi, Kina, 333000
- Jingdezhen First People's Hospital
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Jingdezhen, Jiangxi, Kina, 341000
- The First People's Hospital of Jingdezhen City
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Jiujiang, Jiangxi, Kina
- Jiujiang First People's Hospital
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Liaoning
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Dalian, Liaoning, Kina, 116000
- Dalian Central Hospital
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Sichuan
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Mianyang, Sichuan, Kina, 621000
- The First People's Hospital of Mianyang (Mianyang 404 Hospital)
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-
Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
Tar imot friske frivillige
Kjønn som er kvalifisert for studier
Beskrivelse
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.
Studieplan
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: Randomisert
- Intervensjonsmodell: Parallell tildeling
- Masking: Dobbelt
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
|
Eksperimentell: 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. |
|
Eksperimentell: 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. |
|
Aktiv komparator: 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. |
Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Proportion of patients with mRS 0-1 at 90 days
Tidsramme: 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
|
Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
mRS score at 90 days
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
|
Andre resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Incidence of symptomatic intracranial hemorrhage (sICH) within 48 hours
Tidsramme: 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
Tidsramme: 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
Tidsramme: 90 days after randomization
|
Proportion of participants who die within 90 days after randomization. |
90 days after randomization
|
Samarbeidspartnere og etterforskere
Sponsor
Samarbeidspartnere
Etterforskere
- Hovedetterforsker: zhongming qiu, Xinqiao Hospital of the Army Medical University
Publikasjoner og nyttige lenker
Studierekorddatoer
Studer hoveddatoer
Studiestart (Antatt)
Primær fullføring (Antatt)
Studiet fullført (Antatt)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Faktiske)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Ytterligere relevante MeSH-vilkår
Andre studie-ID-numre
- INSTANT-2
Plan for individuelle deltakerdata (IPD)
Planlegger du å dele individuelle deltakerdata (IPD)?
IPD-planbeskrivelse
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.
IPD-delingstidsramme
Available starting 6 months after publication of the primary manuscript.
Tilgangskriterier for IPD-deling
Interested researchers may submit a formal research proposal and data access request to the corresponding author. The study steering committee will review each application.
IPD-deling Støtteinformasjonstype
- STUDY_PROTOCOL
- SEVJE
- ICF
- ANALYTIC_CODE
- CSR
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