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
Studieoversikt
Status
Forhold
Intervensjon / Behandling
Detaljert beskrivelse
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
Registrering (Antatt)
Fase
- Fase 3
Kontakter og plasseringer
Studiekontakt
- Navn: Bo Song, MD
- Telefonnummer: +86-371-66278068
- E-post: fccsongb@zzu.edu.cn
Studiesteder
-
-
Henan
-
Zhengzhou, Henan, Kina
- Department of Neurology, the First Affiliated Hospital of Zhengzhou University
-
Ta kontakt med:
- Bo Song, MD
- Telefonnummer: +86-371-66278068
- E-post: fccsongb@zzu.edu.cn
-
-
Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
- Voksen
- Eldre voksen
Tar imot friske frivillige
Beskrivelse
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.
Studieplan
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: Randomisert
- Intervensjonsmodell: Parallell tildeling
- Masking: Firemannsrom
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
|
Eksperimentell: 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)
|
|
Aktiv komparator: 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).
|
Asprin (300mg)
rhPro-UK(placebo)
|
Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Modified Rankin Scale (mRS)
Tidsramme: 90 ± 7 days]
|
Proportion of subjects of excellent outcome defined as mRS (0-1) at 90 ± 7 days.
|
90 ± 7 days]
|
Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Modifisert Rankin-skala (mRS)
Tidsramme: 90 ± 7 dager
|
Andel av deltakere med utmerket resultat definert som mRS (0–2) ved 90 ± 7 dager.
|
90 ± 7 dager
|
|
Modified Rankin Scale (mRS)
Tidsramme: 90 ± 7 dager
|
Ordinal skiftanalyse av mRS ved 90 dager
|
90 ± 7 dager
|
|
National Institutes of Health Stroke-skala (NIHSS)
Tidsramme: 24 timer og 7 dager
|
NIHSS-endring fra utgangspunktet etter 24 timer og 7 dager.
|
24 timer og 7 dager
|
|
Barthel (BI)
Tidsramme: 90 ± 7 dager
|
Barthel-indeks score ved 90 ± 7 dager.
|
90 ± 7 dager
|
|
EuroQol 5-Dimensjon (EQ-5D)
Tidsramme: 90 ± 7 dager
|
Livskvalitet målt med EQ-5D-skala ved 90 ± 7 dager.
|
90 ± 7 dager
|
|
Modifisert Rankin-skala (mRS)
Tidsramme: 90 ± 7 dager
|
|
90 ± 7 dager
|
Andre resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Død
Tidsramme: 90 dager
|
Total dødelighet ved 90 dager.
|
90 dager
|
|
Symptomatisk intrakraniell blødning (sICH)
Tidsramme: 36 timer
|
Andel pasienter med symptomatisk intrakraniell blødning (sICH) etter 36 timer (i henhold til ECASS III-kriteriene).
|
36 timer
|
|
Systemisk blødning
Tidsramme: 90 dager
|
Systemisk blødning ved 90 dager (i henhold til GUSTO-kriteriene)
|
90 dager
|
|
Bivirkninger (AEs)/ alvorlige bivirkninger (SAEs)
Tidsramme: 90 dager
|
Andel pasienter med bivirkninger (AEs) / alvorlige bivirkninger (SAEs) innen 90 dager.
|
90 dager
|
Samarbeidspartnere og etterforskere
Studierekorddatoer
Studer hoveddatoer
Studiestart (Antatt)
Primær fullføring (Antatt)
Studiet fullført (Antatt)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Faktiske)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Nøkkelord
Ytterligere relevante MeSH-vilkår
- Cerebrovaskulære lidelser
- Hjernesykdommer
- Sykdommer i sentralnervesystemet
- Sykdommer i nervesystemet
- Vaskulære sykdommer
- Kardiovaskulære sykdommer
- Slag
- Iskemisk hjerneslag
- Organiske kjemikalier
- Hydrokarboner
- Hydrokarboner, syklisk
- Hydrokarboner, aromatisk
- Fenoler
- Benzenderivater
- Salisylater
- Hydroksybenzoater
- Aspirin
Andre studie-ID-numre
- PROMISE-001
Legemiddel- og utstyrsinformasjon, studiedokumenter
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