ProUrokinase in Mild IsChemic strokE (PUMICE)

Ischemic Stroke Clinical Trial

— PUMICE  

Official title:

Recombinant Human Prourokinase（rhPro-UK）for Injection Versus Standard Medical Treatment for Acute Mild Ischemic Stroke (NIHSS≤5) Within 4.5 Hours After Symptom Onset

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05507645
• Other study ID #: HX-A-2022032
• Status: Recruiting
• Phase: Phase 3
• Start date: October 21, 2022
• Est. completion date: June 2024

Study information

• Verified date: October 2022
• Source: Beijing Tiantan Hospital
• Contact: yongjun wang, MD
• Phone: 13911172565
• Email: yongjunwang111[@]aliyun.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to investigate the safety and efficacy of rhPro-UK (35mg) versus standard medical treatment in acute mild ischemic stroke within 4.5 hours of symptom onset.

Description:

After being informed about the study and potential risks, patients who meet the eligibility requirements will be randomized to recombinant human Prourokinase for injection (rhPro-UK) or standard medical treatment in a 1:1 ratio. Written informed consent will be needed.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1446
• Est. completion date: June 2024
• Est. primary completion date: January 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Age =18 years, any gender;

2. Acute ischemic stroke symptom onset within 4.5 hours prior to enrollment; onset time refers to 'last normal time';

3. Pre-stroke mRS score= 1;

4. Baseline NIHSS = 5 (both included);

5. Written informed consent from patients or their legally authorized representatives

Exclusion Criteria:

1. Rapidly improving symptoms at the discretion of the investigator;

2. Intended to proceed to endovascular treatment during 90 days (including mechanical thrombectomy, stent insertion or balloon expansion);

3. Allergy to rhPro-UK and it's components (human albumin, mannitol);

4. NIHSS consciousness score 1a >2, or epileptic seizure, hemiplegia after seizures (Todd's palsy) or combined with other nervous/mental illness unable to cooperate or unwilling to cooperate;

5. Persistent blood pressure elevation (systolic =180 mmHg or diastolic =100 mmHg), despite blood pressure lowering treatment;

6. Blood glucose <2.8 or >22.2 mmol/L (on random glucose testing is acceptable);

7. Active internal bleeding or at high risk of bleeding, e.g.: Major surgery, trauma or gastrointestinal or urinary tract haemorrhage within the previous 21 days, or arterial puncture at a non-compressible site within the previous 7 days;

8. Any known impairment in coagulation due to comorbid disease or anticoagulant use. If on warfarin, then INR >1.7 or prothrombin time >15 seconds; if use of any direct thrombin inhibitors or direct factor Xa inhibitors or new oral anticoagulants (NOAC) during the last 48 hours unless reversal of effect can be achieved with a reversal agent (by idarucizumab) or sensitivity laboratory test values greater than the upper limit of normal (eg, activated partial thromboplastin time (aPTT), international normalized ratio (INR), platelet count, thrombin time (TT), or appropriate factor Xa activity assay); if on any full dose heparin/heparinoid during the last 24 hours or with an elevated aPTT greater than the upper limit of normal;

9. Known defect of platelet function or platelet count below 100,000/mm3 (but patients on antiplatelet agents can be included);

10. Ischemic stroke or myocardial infarction in previous 3 months, previous intracranial haemorrhage, severe traumatic brain injury or intracranial or intraspinal operation in previous 3 months, or known intracranial neoplasm (except for neuroectodermal tumors, such as meningiomas), arteriovenous malformation or giant aneurysm;

11. Any terminal illness such that patient would not be expected to survive more than 1 year

12. Large cerebral infarction (infarct size > 1/3 MCA territory) on CT or MRI;

13. Acute or past intracerebral hemorrhage (ICH) identified by CT or MRI (including intraparenchymal hemorrhage, intraventricular hemorrhage, subarachnoid hemorrhage, subdural/epidural hematoma);

14. Pregnant women, nursing mothers, or reluctant to agree taking effective contraceptive measures during the period of trial subjects;

15. 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;

16. Participation in other interventional clinical trials within the previous 3 months.

Related Conditions & MeSH terms

• Cerebral Infarction
• Ischemia
• Ischemic Stroke
• Stroke
• Thrombosis

Intervention

Drug:
• Recombinant Human Prourokinase for Injection (rhPro-UK)
15mg of rhPro-UK intravenous bolus within 3 minutes, and the remaining 20mg intravenous drip within 30 minutes.
• standard medical treatment
Standard antiplatelet or anticoagulant treatment at the discretion of local investigators.

Locations

Country	Name	City	State
China	Beijing Tiantan Hospital, Capital Medical University	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Beijing Tiantan Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The modified Rankin Scale score (mRS) = 1 at 90 days	The proportion of the modified Rankin Scale score (mRS) = 1 at 90 days.	90 days
Secondary	Ordinal distribution of mRS at 90 days	Ordinal distribution of mRS at 90 days	90 days
Secondary	mRS score = 2 at 90 days	The proportion of mRS score = 2 at 90 days	90 days
Secondary	Early neurological functional improvement	Clinical response rate at 24 hours defined as an improvement on NIHSS score = 4 points compared with the initial deficit or NIHSS score = 1 point	24 hours
Secondary	Barthel index of 75-100 points at 90 days	The proportion of Barthel index of 75-100 points at 90 days	90 days
Secondary	Quality of Life (EQ-5D-5L) at 90 days	The value of Quality of Life (EQ-5D-5L) at 90 days	90 days
Secondary	Activities of Daily Living (Lawton IADL) at 90 days	The score of Activities of Daily Living (Lawton IADL) at 90 days	90 days
Secondary	Symptomatic intracranial hemorrhage within 36 hours	The rate of symptomatic intracranial hemorrhage within 36 hours (as defined by ECASS III)	36 hours
Secondary	All-cause death at 90 days	All-cause mortality at 90 days	90 days
Secondary	Systematic bleeding at 90 days	The rate of systematic bleeding at 90 days (as defined by GUSTO: moderate and severe bleeding)	90 days
Secondary	Adverse events (AEs)/ serious adverse events (SAEs) within 90 days	The proportion of AEs/SAEs within 90 days	90 days