Acute Ischemic StrokePhase 3NCT07389460
Intravenous rhPro-UK Before Stroke Thrombectomy in the Extended Time Window (BRIDGE-PUK EXTEND)
A Phase 3 study testing Intravenous rhPro-UK and Endovascular thrombectomy in people with Acute Ischemic Stroke, run by First Affiliated Hospital Xi'an Jiaotong University at 10 sites in China.
Trial summary
This randomized, double-blind, placebo-controlled phase III clinical trial aims to evaluate the efficacy and safety of intravenous recombinant human Prourokinase (rhPro-UK) in acute ischemic stroke patients with large vessel occlusion presenting 4.5-24 hours after last known well. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Ischemic Stroke
- What is being tested?
- Intravenous rhPro-UK and Endovascular thrombectomy
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 820 participants
- Where
- 10 sitesChina
- Study dates
- 7 Apr 2026to 31 Mar 2028
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥18 years;
- Acute ischemic stroke presenting within 4.5-24 hours of last known well;
- No significant pre-stroke functional disability: for age <80 years, pre-stroke modified Rankin scale (mRS) ≤2; for age ≥80 years, prestroke mRS ≤1;
- Baseline NIHSS score ≥6;
- Imaging criteria of BOTH:
- 1. Occlusion on CTA/MRA in one of the following vessels: M1/M2 segment of middle cerebral artery, A1 segment of anterior cerebral artery, V4 segment of vertebral artery, basilar artery, or P1 segment of posterior cerebral artery. For A1, or P1 occlusions, vessel diameter must be ≥0.75 mm; 2. For anterior circulation occlusion: CTP/MRP demonstrating mismatch ratio ≥1.8, absolute mismatch volume ≥15 mL, and ischemic core volume <70 mL; OR have a mismatch between the presence of an abnormal signal on MRI diffusion-weighted imaging and no visible signal change on FLAIR. For posterior circulation occlusion: pc-ASPECTS score ≥6.
- 6. Plan to received endovascular thrombectomy; 7. The patient or their legal representative provides written informed consent.
Who cannot join
- Intracranial hemorrhage confirmed by CT/MRI;
- Onset accompanied by epileptic seizures, resulting in questionable stroke diagnosis and inability to obtain an accurate baseline NIHSS score;
- Women who are pregnant or breastfeeding, or have a positive serum β-HCG test upon admission;
- Already received intravenous thrombolytic after index stroke;
- History of prior intracranial hemorrhage, including cerebral parenchymal hemorrhage, subarachnoid hemorrhage, and subdural/extradural hematoma;
- Active bleeding or bleeding tendency, such as gastrointestinal bleeding, urinary tract bleeding, retinal hemorrhage, etc., or presence of coagulation dysfunction;
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- History of major recent surgery or trauma, such as intracranial or spinal surgery within the past 3 months, major surgery within the past 2 weeks, or severe head trauma within the past 3 weeks;
- Baseline blood glucose <2.8 mmol/L or >22.2 mmol/L;
- Received low molecular weight heparin within 24 hours, or oral anticoagulants with an International Normalized Ratio (INR) >1.7, or thrombin inhibitors within 48 hours, among others;
- Arterial tortuosity or other vascular anomalies precluding endovascular access to target vessel;
- Pre-existing neurological/psychiatric disorders interfering with neurological assessment;
- Space-occupying intracranial tumors (except for small meningiomas);
- Intracranial aneurysm or arteriovenous malformation;
- Terminal illness with life expectancy <6 months;
- Concurrent participation in other investigation clinical trials;
- Presence of other conditions deemed by the investigator as unsuitable for participation in the study.
Trial locations and contacts
10 sites in 1 country. Contact the study team or a site near you to ask about taking part.
10 sites in 1 country
China10 sites, 10 recruiting
- Recruiting
Xuanwu Hospital Capital Medical University
Beijing
Chuanjie Wu, MD, 18911366882, wuchuanjie@xwhosp.org
- Recruiting
The Second Hospital of Dalian Medical University
Dalian, Liaoning
Linyun Zhang, MD, 15940850119, zly542644190@163.com
- Recruiting
The First Hospital of Lanzhou University
Lanzhou, Gansu
Youquan Gu, MD, 139909406189, guyq@lzu.edu.cn
- Recruiting
Loudi Central Hospital
Loudi, Hunan
Cunliang Zhu, MD, 18773882121, 1722291995@qq.com
- Recruiting
The First Affiliated Hospital of Shihezi University
Shihezi, Xinjiang Uygur Autonomous Region
Linzhi Dai, MD, 13677542691, 1805308040@qq.com
- Recruiting
The Third Hospital of Hebei Medical University
Shijiazhuang, Hebei
Pinyuan Zhang, MD, 15028195377, zhpy_76@sina.com
- Recruiting
Shanxi Cardiovascular Hospital
Taiyuan, Shanxi
Weirong Li, MD, 18735133366, weironglee@163.com
- Recruiting
First Affiliated Hospital of Xi'an Jiaotong University
Xi'an, Shaanxi
Fude Liu, MD, 18161823657, liufude101@163.com
- Recruiting
Qinghai Provincial People's Hospital
Xining, Qinghai
Yancheng Lei, MD, 15897188925, leiyancheng7566@163.com
- Recruiting
Henan Provincial People's Hospital
Zhengzhou, Henan
Liangfu Zhu, MD, 13598881630, sumslfzhu@163.com
About this study
Official title: Intravenous rhPro-UK Versus Placebo Before Endovascular Thrombectomy For Stroke Patient With Large Vessel Occlusion In The Extended Time Window: the Randomized, Placebo-controlled, Double-blind Trial (BRIDGE-PUK EXTEND )
This randomized, double-blind, placebo-controlled phase III clinical trial aims to evaluate the efficacy and safety of intravenous recombinant human Prourokinase (rhPro-UK) in acute ischemic stroke patients with large vessel occlusion presenting 4.5-24 hours after last known well. The study will address two primary questions: 1) Whether rhPro-UK enhances pre-thrombectomy reperfusion rates and improves 90-day functional outcomes compared to placebo; 2) Whether rhPro-UK increases the risk of symptomatic intracranial hemorrhage and mortality.
Participants will be randomized to receive an intravenous bolus of rhPro-UK or matching placebo, with a total dose of 35mg (15mg administered as an intravenous push within 5 minutes, and the remaining 20mg continuously infused intravenously over 30 minutes). Key assessments include repeat neuroimaging (CT/CTA or MRI/MRA) at 24 hours post-treatment to evaluate reperfusion, NIH Stroke Scale score at day 5-7, and modified Rankin Scale score assessment at 90 days. Safety monitoring will focus on hemorrhagic transformation and mortality events throughout the study period.
Read the detailed description
This multicenter, phase III trial employs a randomized, double-blind, placebo-controlled design to investigate the therapeutic window extension for rhPro-UK in large vessel occlusion stroke. Eligible participants are adults with large vessel occlusion confirmed by vascular imaging (CTA/MRA), and salvageable brain tissue demonstrated by perfusion imaging (CTP/MRP) mismatch. Exclusion criteria include contraindications to thrombolysis, and large core infarction (>70 mL on CTP).
Patients will be randomized 1:1 to receive either rhPro-UK or placebo, with a total dose of 35mg (15mg administered as an intravenous push within 5 minutes, followed by the remaining 20 mg continuously infused intravenously over 30 minutes) . All participants will undergo endovascular thrombectomy.
The primary outcome is functional independence (mRS 0-2) at 90 days. Secondary outcomes include substantial reperfusion at initial angiogram, first-pass reperfusion, final infarct volume on hour 36 CT, etc. Safety outcomes include symptomatic intracranial hemorrhage per Heidelberg Bleeding Classification criteria within 36 hours, and 90-day mortality.
Safety monitoring includes independent adjudication of hemorrhagic events and all-cause mortality. A sample size of 820 participants provides 80% power to detect a 10% absolute difference in functional independence (α=0.05).
The trial incorporates centralized blinded outcome assessment and intention-to-treat analysis, with data oversight by an independent clinical events committee and data safety monitoring board.
- Conditions
- Acute Ischemic Stroke
- Being tested
- Intravenous rhPro-UK, Intravenous placebo, Endovascular thrombectomy
- Keywords
- Large Vessel Occlusion Stroke, Recombinant Human Prourokinase, Extended Time Window, Intravenous Thrombolytic Therapy, Endovascular Treatment
- Medical subject headings
- Ischemic Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intravenous rhPro-UKDrug
Also called Intravenous PUK, Intravenous recombinant human prourokinase
Patients will receive intravenous rhPro-UK
Intravenous placeboDrug
Also called Intravenous placebo (a visually identical substance without pharmacological activity)
Patients will receive intravenous placebo
Endovascular thrombectomyProcedure or surgery
Also called Endovascular treatment, Mechanical thrombectomy
Patients will receive endovascular thrombectomy
| Study group | Role | What they receive |
|---|---|---|
| rhPro-UK group | Experimental | Patients in this group will be treated with intravenous rhPro-UK and endovascular thrombectomy Receives: Drug: Intravenous rhPro-UK; Procedure: Endovascular thrombectomy |
| Placebo group | Placebo comparator | Patients in this group will be treated with intravenous placebo and endovascular thrombectomy Receives: Drug: Intravenous placebo; Procedure: Endovascular thrombectomy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of patients functionally independent (mRS score 0 to 2) at 90 days
The modified Rankin Scale (mRS) is employed to assess patients' activities of daily living and the degree of disability. It grades patients' functional ability on a scale from 0 to 6, with a score of 0 indicating no symptoms and 6 representing death. An mRS score of 0-2 indicates functional independence.
Measured: 90 days post-randomization
Secondary outcomes (18)
Distribution of mRS scores at 90 days
The Modified Rankin Scale (mRS) is employed to assess patients' activities of daily living and the degree of disability. It grades patients' functional ability on a scale from 0 to 6, with a score of 0 indicating no symptoms and 6 representing death. The mRS score reflects the neurological functional status of stroke patients.
Measured: 90 days post-randomization
Shift in mRS score at 90 days
The modified Rankin Scale (mRS) is employed to assess patients' activities of daily living and the degree of disability. It grades patients' functional ability on a scale from 0 to 6, with a score of 0 indicating no symptoms and 6 representing death. An mRS score shift reflects the improvement in the patient's neurological function.
Measured: 90 days post-randomization
Proportion of excellent functional outcome (mRS score 0 to 1) at 90 days
The modified Rankin Scale (mRS) is employed to assess patients' activities of daily living and the degree of disability. It grades patients' functional ability on a scale from 0 to 6, with a score of 0 indicating no symptoms and 6 representing death. An mRS score of 0-1 indicates excellent functional outcome.
Measured: 90 days post-randomization
Score on the EQ-5D-5L scale at 90 days
The EuroQoL 5-Dimension 5-Level (EQ-5D-5L) is a standardized health-related quality of life measurement instrument developed by the EuroQoL Group, primarily used to assess an individual's health status across multiple dimensions and their overall quality of life. The EQ-5D-5L describes an individual's health state based on five dimensions: Mobility, Self-care, Usual activities, Pain/Discomfort, and Anxiety/Depression. Scores range from 0, representing "the worst imaginable health," to 100, representing "the best imaginable health."
Measured: 90 days post-randomization
Change in NIHSS score from baseline to 5-7 days post-procedure or at discharge
The National Institutes of Health Stroke Scale (NIHSS) is a tool designed for the rapid assessment of neurological deficit severity. Each item is scored from 0 to 4 based on the patient's performance, with a total score ranging from 0 to 42. A higher score indicates a more severe neurological deficit.
Measured: 5-7 days post-procedure or at discharge
NIHSS score at 5-7 days post-procedure or at discharge
The National Institutes of Health Stroke Scale (NIHSS) is a tool designed for the rapid assessment of neurological deficit severity. Each item is scored from 0 to 4 based on the patient's performance, with a total score ranging from 0 to 42. A higher score indicates a more severe neurological deficit.
Measured: 5-7 days post-procedure or at discharge
Final infarct volume on hour 36 NCCT
Infarct volume quantified via NCCT , with manual correction by certified radiologists.
Measured: 36 hours post-randomization
Substantial reperfusion (defined as an eTICI grade of 2b50, 2b67, 2c, or 3) at initial angiogram
The expanded Thrombolysis In Cerebral Infarction (eTICI) reperfusion grading system is a 7-point scale: 0 indicates no reperfusion noted; 1, reduction in thrombus without filling of distal arterial branches; 2a, reperfusion of <50% of the territory; 2b50, a reperfusion of 50-66% of the territory; 2b67, a reperfusion of 67-89% of the territory;2c, near-complete perfusion with distal slow flow or presence of small cortical emboli; and 3, complete reperfusion. Successful reperfusion at initial angiogram prior to thrombectomy was defined as an eTICI grade of 2b50, 2b67, 2c, or 3 on the first intracranial angiogram.
Measured: within 5 minutes at initial angiogram
Successful reperfusion (defined as an eTICI grade of 2b, 2c, or 3) at end-of-procedure angiography
The expanded Thrombolysis In Cerebral Infarction (eTICI) reperfusion grading system is a 7-point scale: 0 indicates no reperfusion noted; 1, reduction in thrombus without filling of distal arterial branches; 2a, reperfusion of <50% of the territory; 2b50, a reperfusion of 50-66% of the territory; 2b67, a reperfusion of 67-89% of the territory;2c, near-complete perfusion with distal slow flow or presence of small cortical emboli; and 3, complete reperfusion. This outcome will be evaluate at the end of procedure.
Measured: 15 minutes after initial angiogram
Modified first-pass reperfusion
defined as Expanded Treatment in Cerebral Infarction 2b50, 2b67, 2c, or 3 after the first thrombectomy pass
Measured: Perioperative (After artery puncture, but the start of procedure)
Time from arterial puncture to successful recanalization or final angiography
The time (in minutes) from arterial puncture to successful recanalization or the final angiogram, reflecting the duration of the procedure.
Measured: Intraoperative
Proportion of balloon angioplasty or stent placement during endovascular treatment
Endovascular treatment includes procedures such as thrombectomy, balloon angioplasty, and stent placement. This outcome specifically focuses on the proportion of patients undergoing balloon angioplasty or stent placement during endovascular therapy.
Measured: Intraoperative
Proportion of patients planned for but ultimately not receiving endovascular treatment
Patients planned for endovascular treatment may fail to undergo the procedure due to various reasons, including economic factors, disagreement among legal representatives, and changes in clinical condition, among others. This outcome focuses on the proportion of patients who were scheduled to receive but ultimately did not undergo endovascular treatment.
Measured: Perioperative (After artery puncture, but the start of procedure)
Symptomatic intracranial hemorrhage within 36 hours
evaluate intracranial hemorrhage (Heidelberg classification)
Measured: within 36 hours after endovascular treatment
Proportion of patients with parenchymal hematoma at 36 hours post-procedure
European Cooperative Acute Stroke Study (ECASS) classification: Hemorrhagic infarction (HI) is divided into: HI1: Small petechial hemorrhages along the margins of the infarct. HI2: Confluent or multiple scattered petechial hemorrhages within the infarcted area. Parenchymal hematoma (PH) is divided into: PH1: Hematoma occupying ≤30% of the infarcted area, with mild mass effect. PH2: Hematoma occupying >30% of the infarcted area, with significant mass effect. This outcome will be evaluate the proportion of patients with PH2-type (parenchymal hematoma type 2) at 36 hours postoperatively.
Measured: within 36 hours after endovascular treatment
Mortality within 90 days
evaluate death rate of the two treatment groups
Measured: 90 days post-randomization
Procedural-related complications
evaluate complications
Measured: within 90 days
Severe adverse events
evaluate any adverse events
Measured: within 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Feb 2026
- Study start7 Apr 2026
- Primary completion31 Dec 2027 (estimated)
- Study completion31 Mar 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Ischemic StrokeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 820 participants (estimated)
Sponsor and investigators
- Lead sponsor
- First Affiliated Hospital Xi'an Jiaotong University
- Sponsor type
- University, hospital or other
- Collaborators
- Tasly Pharmaceutical Group Co., Ltd, Peking Union Medical College Hospital
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07389460
- Sponsor's protocol ID
- XJTU1AF2026LSYY-0065
- Other IDs
- BRIDGE-PUK EXTEND
- Status last verified
- Sep 2026
- First submitted
- 27 Jan 2026
- Last updated
- 9 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: study data without patient information