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
연구 개요
상세 설명
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.
연구 유형
등록 (추정된)
단계
- 3단계
연락처 및 위치
연구 연락처
- 이름: Bo Song, MD
- 전화번호: +86-371-66278068
- 이메일: fccsongb@zzu.edu.cn
연구 장소
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Henan
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Zhengzhou, Henan, 중국
- Department of Neurology, the First Affiliated Hospital of Zhengzhou University
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연락하다:
- Bo Song, MD
- 전화번호: +86-371-66278068
- 이메일: fccsongb@zzu.edu.cn
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참여기준
자격 기준
공부할 수 있는 나이
- 성인
- 고령자
건강한 자원 봉사자를 받아들입니다
설명
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.
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위
- 중재 모델: 병렬 할당
- 마스킹: 네 배로
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
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실험적: 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).
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rhPro-UK (5 mg/vial), to maximum of 35mg
Asprin (placebo)
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활성 비교기: 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).
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아스피린 (300mg)
rhPro-UK(placebo)
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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Modified Rankin Scale (mRS)
기간: 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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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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수정 랭킨 척도 (mRS)
기간: 90 ± 7일
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90±7일 시점에서 mRS(0-2)로 정의된 우수한 결과를 보인 대상자의 비율.
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90 ± 7일
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수정된 랭킨 척도 (mRS)
기간: 90 ± 7일
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90일 mRS의 순위 이동 분석
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90 ± 7일
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국립보건원 뇌졸중 척도(NIHSS)
기간: 24시간 및 7일
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24시간 및 7일째 기준선 대비 NIHSS 변화.
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24시간 및 7일
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바르텔 (BI)
기간: 90 ± 7일
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Barthel Index 점수 (90 ± 7일).
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90 ± 7일
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EuroQol 5-Dimension (EQ-5D)
기간: 90 ± 7일
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EQ-5D 척도로 측정된 삶의 질 (90 ± 7일).
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90 ± 7일
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수정된 랭킨 척도 (mRS)
기간: 90 ± 7일
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90 ± 7일
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기타 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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죽음
기간: 90일
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90일째 전체 사망률.
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90일
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증상성 두개내 출혈 (sICH)
기간: 36시간
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36시간 내에 증상성 두개내 출혈(sICH)이 발생한 대상자의 비율(ECASS III 기준에 따름).
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36시간
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전신 출혈
기간: 90일
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90일 시점의 전신 출혈 (GUSTO 기준에 따름)
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90일
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부작용(AE)/중대한 부작용(SAE)
기간: 90일
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90일 이내에 부작용(AEs)/심각한 부작용(SAEs)이 발생한 환자의 비율.
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90일
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공동 작업자 및 조사자
연구 기록 날짜
연구 주요 날짜
연구 시작 (추정된)
기본 완료 (추정된)
연구 완료 (추정된)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (실제)
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
키워드
추가 관련 MeSH 약관
기타 연구 ID 번호
- PROMISE-001
약물 및 장치 정보, 연구 문서
미국 FDA 규제 의약품 연구
미국 FDA 규제 기기 제품 연구
미국에서 제조되어 미국에서 수출되는 제품
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