Pro-urokinase for Extended-Window Posterior Circulation Stroke (PROMISE)
Pro-urokinase for Reperfusion in Acute pOsterior Circulation ischeMIc Stroke in the Extended Window (the PROMISE Trail): A Randomized, Double-blind, Baseline Treatment-controlled Study
調査の概要
詳細な説明
Stroke is the second leading cause of death and the third leading cause of disability worldwide. Posterior circulation ischemic stroke (PCIS) accounts for approximately 20% of all ischemic strokes. Due to involvement of critical structures such as the brainstem and cerebellum, PCIS is associated with rapid neurological deterioration, high disability and mortality rates, and often presents with atypical clinical manifestations, leading to frequent misdiagnosis and delayed treatment. Consequently, many patients miss the conventional 4.5-hour intravenous thrombolysis window. However, the posterior circulation possesses relatively abundant collateral circulation and stronger ischemic tolerance, resulting in a lower risk of intracranial hemorrhage after thrombolysis and suggesting the potential feasibility of an extended therapeutic window.
In recent years, multiple studies have promoted a paradigm shift in acute ischemic stroke management from a "time window"-based strategy to a "tissue window"-based strategy. Trials including EXTEND, TRACE-III, HOPE, and OPTION demonstrated that intravenous thrombolysis administered within 4.5-24 hours after symptom onset, guided by perfusion imaging selection, could still improve functional outcomes. The EXPECTS study further showed that patients with posterior circulation stroke who were not candidates for endovascular thrombectomy could benefit from alteplase treatment within 4.5-24 hours, with a relatively low risk of symptomatic intracranial hemorrhage. Nevertheless, limitations such as a high proportion of mild stroke cases, non-randomized study design, and baseline imbalance indicate that stronger evidence is still required.
Recombinant human prourokinase (rhPro-UK), a novel fibrin-specific thrombolytic agent independently developed in China, has advantages over rt-PA, including lower systemic fibrinolytic activation and reduced bleeding risk, making it potentially more suitable for extended-window thrombolysis. The PROST-2 trial demonstrated that rhPro-UK was non-inferior to rt-PA in efficacy among patients treated within 4.5 hours after acute ischemic stroke onset, while significantly reducing symptomatic intracranial hemorrhage and systemic bleeding events, highlighting its favorable safety profile and potential for extended-window application.
Therefore, this study aims to evaluate whether intravenous thrombolysis with rhPro-UK, compared with standard medical therapy, can achieve better 90-day functional outcomes and improved safety in patients with imaging-confirmed posterior circulation acute ischemic stroke presenting within 4.5-24 hours after symptom onset and not scheduled for endovascular thrombectomy.
研究の種類
入学 (推定)
段階
- フェーズ 3
連絡先と場所
研究連絡先
- 名前：Bo Song, MD
- 電話番号：+86-371-66278068
- メール：fccsongb@zzu.edu.cn
研究場所
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Henan
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Zhengzhou、Henan、中国
- Department of Neurology, the First Affiliated Hospital of Zhengzhou University
-
コンタクト：
- Bo Song, MD
- 電話番号：+86-371-66278068
- メール：fccsongb@zzu.edu.cn
-
-
参加基準
適格基準
就学可能な年齢
- 大人
- 高齢者
健康ボランティアの受け入れ
説明
Inclusion Criteria:
- Age ≥ 18 years;
- AIS with symptom onset 4.5-9 hours before enrollment, including wake-up stroke and unwitnessed stroke (onset time defined as when symptoms were first noticed);
Imaging criteria:
- DWI-FLAIR mismatch: visible lesion on DWI with no marked visible lesion on FLAIR;
- DWI infarct core not exceeding one-third of the middle cerebral artery territory, one-half of the anterior cerebral artery territory, or one-half of the posterior cerebral artery territory;
- NIHSS score 4-25;
- First-ever stroke or previous stroke without significant disability (pre-stroke mRS ≤ 1);
- Signed informed consent from the patient or legally authorized representative.
Exclusion Criteria:
- Planned endovascular treatment;
- Contradictory to MRI examination;
- MRI image not qualified for evaluation;
- Serious neurological deficits before onset (mRS≥2);
- Obvious head injuries or strokes within 3 months;
- Subarachnoid or intracranial hemorrhage;
- History of intracranial hemorrhage;
- Intracranial tumor, arteriovenous malformation or aneurysm;
- Intracranial or spinal cord surgery within 3 months;
- Active internal hemorrhage;
- platelet count of <100000/mm3;
- Aortic arch dissection;
- Heparin therapy within 24 hours;
- Oral warfarin is being taken and INR>1.6 or APTT abnormal;
- Oral anticoagulation therapy;
- Systolic pressure≥185 mmHg or diastolic pressure≥110 mmHg;
- Blood glucose < 50 mg/dl (2.7mmol/L);
- Pregnancy;
- Neurological deficit after epileptic seizures;
- Major surgery within 1 month;
- Gastrointestinal or urinary tract hemorrhage within the previous 30 days;
- Myocardial infarction within 3 months;
- Allergy to study drugs;
- Unlikely to adhere to the trial protocol or follow-up;
- Any condition that, in the judgment of the investigator could impose hazards to the patient if study therapy is initiated or affect the participation of the patient in the study;
- Participation in other interventional clinical trials within the previous 3 months.
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：4倍
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
実験的：rhPro-UK group
On Day 1 after randomization, patients will receive intravenous rhPro-UK plus aspirin placebo (300 mg).
From day 2 to day 90, patients will receive standard care according to the Chinese Guidelines for Diagnosis and Treatment of Acute Ischemic Stroke (2023).
|
rhPro-UK (5 mg/vial), to maximum of 35mg
Asprin (placebo)
|
|
アクティブコンパレータ：Control group
On Day 1 after randomization, patients will receive rhPro-UK placebo plus oral aspirin (300 mg).
From day 2 to day 90, patients will receive standard care according to the Chinese Guidelines for Diagnosis and Treatment of Acute Ischemic Stroke (2023).
|
アスピリン（300mg）
rhPro-UK(placebo)
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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 |
|---|---|---|
|
Modified Rankin Scale (mRS)
時間枠：90 ± 7 days]
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Proportion of subjects of excellent outcome defined as mRS (0-1) at 90 ± 7 days.
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90 ± 7 days]
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
修正ランキンスケール (mRS)
時間枠：90 ± 7 日
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90日±7日時点でmRS（0-2）と定義された良好な転帰を示した被験者の割合。
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90 ± 7 日
|
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Modified Rankin Scale (mRS)
時間枠：90 ± 7 日
|
90日時点のmRSの順位シフト分析
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90 ± 7 日
|
|
国立衛生研究所脳卒中スケール (NIHSS)
時間枠：24時間と7日間
|
NIHSS変化：ベースラインからの変化を24時間および7日後に評価
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24時間と7日間
|
|
バーセル (BI)
時間枠：90 ± 7 日
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90 ± 7日時点でのBarthel Indexスコア。
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90 ± 7 日
|
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EuroQol 5次元（EQ-5D）
時間枠：90 ± 7 日
|
EQ-5Dスケールによる生活の質を90±7日で測定。
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90 ± 7 日
|
|
Modified Rankin Scale (mRS)
時間枠：90 ± 7 日
|
|
90 ± 7 日
|
その他の成果指標
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
死
時間枠：90日
|
90日での全体的な死亡率。
|
90日
|
|
症状性頭蓋内出血（sICH）
時間枠：36時間
|
36時間時点における症状性頭蓋内出血（sICH）の被験者の割合（ECASS III基準による）。
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36時間
|
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全身性出血
時間枠：90日
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90日時点の全身性出血（GUSTO基準による）
|
90日
|
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有害事象（AEs）／重篤な有害事象（SAEs）
時間枠：90日
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90日以内の有害事象（AEs）／重篤な有害事象（SAEs）を有する患者の割合。
|
90日
|
協力者と研究者
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
キーワード
追加の関連 MeSH 用語
その他の研究ID番号
- PROMISE-001
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
米国で製造され、米国から輸出された製品。
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