Ischemic Stroke, Acute
Conditions
Brief summary
LUMEN is a multicenter, randomized, double-blind, placebo-controlled superiority trial designed to evaluate whether oral lumbrokinase enteric-coated capsules combined with aspirin improve functional outcomes compared with aspirin alone in patients with moderate-to-severe acute ischemic stroke. Eligible adults aged 18-80 years with a baseline NIHSS score of 4-20, prestroke mRS ≤1, and onset within 24 hours are randomly assigned 1:1 to receive either lumbrokinase (600,000 IU, three times daily for 28 days) plus aspirin 100 mg daily for 90 days, or matching placebo plus aspirin 100 mg daily for 90 days. All participants receive standard medical care according to guidelines. The primary efficacy endpoint is the proportion of patients achieving an excellent functional outcome (modified Rankin Scale score 0-1) at 90 days. The primary safety endpoint is the incidence of severe or moderate bleeding (GUSTO definition) within 90 days.
Interventions
DRUGLumbrokinase
Participants receive lumbrokinase enteric-coated capsules 600,000 IU per dose, three times daily, 30 minutes before meals, for 28 days, plus oral aspirin 100 mg once daily for 90 days. Study drug is started as soon as possible after randomization. Guideline-based standard medical care for acute ischemic stroke is provided throughout.
DRUGLumbrokinase Placebo
Participants receive matching placebo enteric-coated capsules (identical to lumbrokinase capsules in appearance, odor, taste, and packaging) 600,000 IU-equivalent per dose, three times daily, 30 minutes before meals, for 28 days, plus oral aspirin 100 mg once daily for 90 days. Guideline-based standard medical care for acute ischemic stroke is provided throughout.
Sponsors
Xinqiao Hospital of Chongqing
The First Affiliated Hospital of Nanchang University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Age 18-80 years; * Acute ischemic stroke confirmed by CT or MRI; * Baseline NIHSS score 4-20 at enrollment; * Good prestroke functional status (mRS ≤1); * Randomization within 24 hours of last known well; * Written informed consent provided by the participant or legal representative.
Exclusion criteria
* Received or planned intravenous thrombolysis or endovascular treatment after stroke onset; * Cardioembolic stroke (atrial fibrillation, heart valve replacement, atrial myxoma, endocarditis, etc.); * Other causative etiologies of stroke (aortic dissection, cervico-cerebral arterial dissection, vasculitis, vascular malformation, moyamoya disease/syndrome, fibromuscular dysplasia, etc.); * Non-vascular neurological diseases (intracranial tumor, multiple sclerosis, etc.); * Accompanying hemorrhagic transformation of infarction; * Concomitant use of other fibrinolytic therapy (e.g., urokinase, batroxobin, snake-venom preparations) or anticoagulant therapy (e.g., argatroban, rivaroxaban, dabigatran); * Severe hepatic insufficiency (ALT or AST \>2 × upper limit of normal) or renal insufficiency (creatinine \>1.5 × ULN or eGFR \<40 mL/min/1.73 m²), or coagulopathy, or systemic bleeding, or thrombocytopenia (\<100×10⁹/L); * History of intracranial hemorrhage (e.g., intracerebral hemorrhage or subarachnoid hemorrhage); * Bleeding diathesis or major surgery within 90 days (gastrointestinal bleeding, hemoptysis, etc.); * Hypersensitivity to lumbrokinase or aspirin; * Planned surgery or vascular reconstruction within 90 days that may require study-drug interruption; * History of malignancy or aneurysm (including intracranial or peripheral aneurysm); * Received lumbrokinase or other fibrinolytic therapy within 14 days prior to randomization; * Pregnancy or lactation; * Participation in another clinical trial; * Prior neurological or psychiatric disease that would interfere with neurological assessment; * Expected survival less than 90 days; * Expected inability to complete follow-up.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of patients with mRS 0-1 at 90 days | At 90 days after randomization | Proportion of participants achieving an excellent functional outcome, defined as a modified Rankin Scale (mRS) score of 0 (no symptoms) or 1 (no significant disability despite some symptoms) at 90 days after randomization. |
| Incidence of severe or moderate bleeding (GUSTO definition) within 90 days | Within 90 days after randomization | Proportion of participants experiencing severe or moderate bleeding within 90 days, assessed using the GUSTO bleeding classification. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 90-day mRS score distribution (ordinal shift analysis) | At 90 days after randomization | 90-day mRS score distribution (ordinal shift analysis) |
| Change in fibrinogen level from randomization to day 28 | At 28 days after randomization | Change in fibrinogen level from randomization to day 28 |
| Change in hs-CRP level from randomization to day 28 | At 28 days after randomization | Change in hs-CRP level from randomization to day 28 |
| Change in prothrombin time (PT) from randomization to day 28 | At 28 days after randomization | Change in prothrombin time (PT) from randomization to day 28 |
| Change in activated partial thromboplastin time (APTT) from randomization to day 28 | At 28 days after randomization | Change in activated partial thromboplastin time (APTT) from randomization to day 28 |
| Proportion of participants with mRS 0-2 at 90 days | At 90 days after randomization | Proportion of participants with mRS 0-2 at 90 days |
| 90-day EQ-5D-5L score | At 90 days after randomization | 90-day EQ-5D-5L score |
| NIHSS score at 5-7 days after randomization | At 5-7 days after randomization | NIHSS score at 5-7 days after randomization |
| Composite vascular events within 90 days (ischemic stroke, intracranial hemorrhage, myocardial infarction, vascular death) | Within 90 days after randomization | Composite vascular events within 90 days (ischemic stroke, intracranial hemorrhage, myocardial infarction, vascular death) |
| Ischemic stroke recurrence rate within 90 days | Within 90 days after randomization | Ischemic stroke recurrence rate within 90 days |
| Proportion with intracranial hemorrhage within 90 days | Within 90 days after randomization | Proportion with intracranial hemorrhage within 90 days |
| All bleeding events within 90 days | Within 90 days after randomization | All bleeding events within 90 days (including severe/moderate bleeding and intracranial hemorrhage) |
| All-cause mortality within 90 days | Within 90 days after randomization | All-cause mortality within 90 days |
| Investigator-reported adverse events / serious adverse events within 90 days | Within 90 days after randomization | Investigator-reported adverse events / serious adverse events within 90 days |
Contacts
CONTACTDaojun Hong, MD
CONTACTJing Lin, MD
PRINCIPAL_INVESTIGATORZhongming Qiu
Xinqiao Hospital of the Army Medical University
Outcome results
None listed