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.
調査の概要
研究の種類
入学 (推定)
段階
- フェーズ2
- フェーズ 3
連絡先と場所
研究連絡先
- 名前：Guoyong Zeng, doctor
- 電話番号：+8613507079530
- メール：hsyygy@126.com
研究連絡先のバックアップ
- 名前：Fan Zhang, doctor
- 電話番号：+8618970148470
- メール：zhappy0066@126.com
研究場所
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Anhui
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Fuyang、Anhui、中国、236600
- Taihe County People's Hospital
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Fujian
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Longyan、Fujian、中国、364000
- Longyan First Hospital of Fujian Medical University
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Hunan
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Xiangtan、Hunan、中国、411100
- Xiangtan Central Hospital (The Affiliated Hospital of Hunan University)
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Jiangxi
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Ganzhou、Jiangxi、中国、341000
- Ganzhou People's Hospital
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Ganzhou、Jiangxi、中国、342414
- Xingguo People's Hospital, Xinguo Hospital of Gannan Medical University
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Jingdezhen、Jiangxi、中国、333000
- Jingdezhen First People's Hospital
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Jingdezhen、Jiangxi、中国、341000
- The First People's Hospital of Jingdezhen City
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Jiujiang、Jiangxi、中国
- Jiujiang First People's Hospital
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Liaoning
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Dalian、Liaoning、中国、116000
- Dalian Central Hospital
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Sichuan
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Mianyang、Sichuan、中国、621000
- The First People's Hospital of Mianyang (Mianyang 404 Hospital)
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
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.
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：ダブル
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
実験的：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. |
|
実験的：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. |
|
アクティブコンパレータ：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. |
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Proportion of patients with mRS 0-1 at 90 days
時間枠：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
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
mRS score at 90 days
時間枠：90 days after randomization
|
Modified Rankin Scale (mRS) score assessed at 90 days after randomization. |
90 days after randomization
|
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EQ-5D-5L score at 90 days
時間枠：90 days after randomization
|
EQ-5D-5L questionnaire score assessed at 90 days after randomization. |
90 days after randomization
|
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Proportion of patients with mRS 0-2 at 90 days
時間枠：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
時間枠：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
時間枠：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
|
その他の成果指標
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Incidence of symptomatic intracranial hemorrhage (sICH) within 48 hours
時間枠：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
|
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Incidence of any intracranial hemorrhage (any ICH) within 48 hours
時間枠：Within 48 hours after randomization
|
Proportion of participants with any intracranial hemorrhage (any ICH) within 48 hours after randomization. |
Within 48 hours after randomization
|
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90-day mortality
時間枠：90 days after randomization
|
Proportion of participants who die within 90 days after randomization. |
90 days after randomization
|
協力者と研究者
捜査官
- 主任研究者：zhongming qiu、Xinqiao Hospital of the Army Medical University
出版物と役立つリンク
研究記録日
主要日程の研究
研究開始 (推定)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- INSTANT-2
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
IPD プランの説明
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 共有時間枠
Available starting 6 months after publication of the primary manuscript.
IPD 共有アクセス基準
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 共有サポート情報タイプ
- STUDY_PROTOCOL
- SAP
- ICF
- ANALYTIC_CODE
- CSR
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
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