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
Studie Overzicht
Toestand
Conditie
Interventie / Behandeling
Gedetailleerde beschrijving
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.
Studietype
Inschrijving (Geschat)
Fase
- Fase 3
Contacten en locaties
Studiecontact
- Naam: Bo Song, MD
- Telefoonnummer: +86-371-66278068
- E-mail: fccsongb@zzu.edu.cn
Studie Locaties
-
-
Henan
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Zhengzhou, Henan, China
- Department of Neurology, the First Affiliated Hospital of Zhengzhou University
-
Contact:
- Bo Song, MD
- Telefoonnummer: +86-371-66278068
- E-mail: fccsongb@zzu.edu.cn
-
-
Deelname Criteria
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
- Volwassen
- Oudere volwassene
Accepteert gezonde vrijwilligers
Beschrijving
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.
Studie plan
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: Gerandomiseerd
- Interventioneel model: Parallelle opdracht
- Masker: Verviervoudigen
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
|---|---|
|
Experimenteel: 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)
|
|
Actieve vergelijker: 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).
|
Aspirine (300mg)
rhPro-UK(placebo)
|
Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
|
Modified Rankin Scale (mRS)
Tijdsspanne: 90 ± 7 days]
|
Proportion of subjects of excellent outcome defined as mRS (0-1) at 90 ± 7 days.
|
90 ± 7 days]
|
Secundaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
|
Modified Rankin Scale (mRS)
Tijdsspanne: 90 ± 7 dagen
|
Aandeel van proefpersonen met een uitstekende uitkomst, gedefinieerd als mRS (0-2) na 90 ± 7 dagen.
|
90 ± 7 dagen
|
|
Modified Rankin Scale (mRS)
Tijdsspanne: 90 ± 7 dagen
|
Ordinale verschuivinganalyse van mRS na 90 dagen
|
90 ± 7 dagen
|
|
National Institutes of Health Stroke Scale (NIHSS)
Tijdsspanne: 24 uur en 7 dagen
|
NIHSS-verandering vanaf baseline na 24 uur en 7 dagen.
|
24 uur en 7 dagen
|
|
Barthel (BI)
Tijdsspanne: 90 ± 7 dagen
|
Barthel Index score na 90 ± 7 dagen.
|
90 ± 7 dagen
|
|
EuroQol 5-Dimension (EQ-5D)
Tijdsspanne: 90 ± 7 dagen
|
Kwaliteit van leven gemeten met de EQ-5D-schaal op 90 ± 7 dagen.
|
90 ± 7 dagen
|
|
Modified Rankin Scale (mRS)
Tijdsspanne: 90 ± 7 dagen
|
|
90 ± 7 dagen
|
Andere uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
|
Dood
Tijdsspanne: 90 dagen
|
Algeheel sterftecijfer na 90 dagen.
|
90 dagen
|
|
Symptomatische intracraniële bloeding (sICH)
Tijdsspanne: 36 uur
|
Aandeel proefpersonen met symptomatische intracraniële bloeding (sICH) na 36 uur (volgens de ECASS III-criteria).
|
36 uur
|
|
Systemische bloeding
Tijdsspanne: 90 dagen
|
Systemische bloeding na 90 dagen (volgens de GUSTO-criteria)
|
90 dagen
|
|
Bijwerkingen (AEs)/ ernstige bijwerkingen (SAEs)
Tijdsspanne: 90 dagen
|
Proportie van patiënten met bijwerkingen (AEs)/ ernstige bijwerkingen (SAEs) binnen 90 dagen.
|
90 dagen
|
Medewerkers en onderzoekers
Studie record data
Bestudeer belangrijke data
Studie start (Geschat)
Primaire voltooiing (Geschat)
Studie voltooiing (Geschat)
Studieregistratiedata
Eerst ingediend
Eerst ingediend dat voldeed aan de QC-criteria
Eerst geplaatst (Werkelijk)
Updates van studierecords
Laatste update geplaatst (Werkelijk)
Laatste update ingediend die voldeed aan QC-criteria
Laatst geverifieerd
Meer informatie
Termen gerelateerd aan deze studie
Trefwoorden
Aanvullende relevante MeSH-voorwaarden
- Cerebrovasculaire aandoeningen
- Hersenziekten
- Ziekten van het centrale zenuwstelsel
- Ziekten van het zenuwstelsel
- Vaatziekten
- Hart-en vaatziekten
- Hartinfarct
- Ischemische beroerte
- Organische chemicaliën
- Koolwaterstoffen
- Koolwaterstoffen, cyclisch
- Koolwaterstoffen, aromatisch
- Fenolen
- Benzeenderivaten
- Salicyen
- Hydroxybenzoates
- Aspirine
Andere studie-ID-nummers
- PROMISE-001
Informatie over medicijnen en apparaten, studiedocumenten
Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel
Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct
product vervaardigd in en geëxporteerd uit de V.S.
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