Efficacy and Safety of Human Urinary Kallidinogenase for Acute Ischemic Stroke Patients Receiving Reperfusion Treatment

Not Applicable

Recruiting

• Conditions: Acute Ischemic Stroke
• Interventions: Drug: Human urinary kallidinogenase (HUK); Drug: Placebo

• Registration Number: NCT06848894
• Lead Sponsor: Beijing Tiantan Hospital

Brief Summary

This study aims to explore the efficacy and safety of Human Urinary Kallidinogenase for acute ischemic stroke patients receiving intravenous thrombolysis and/or endovascular treatment.

Detailed Description

Within 24 hours after symptom onset, eligible participants will be randomly assigned in a 1:1 ratio to the HUK or placebo group, receiving adjunctive HUK or placebo treatment alongside standard intravenous thrombolysis and/or endovascular treatment. All participants will be recommended to continuously inject drugs or placebo for 10 to 14 days according to length of hospitalization.

* Intervention group: HUK (0.15 PNA) and sodium chloride injection (100ml), once per day

* Control group: placebo (0 PNA) and sodium chloride injection (100ml), once per day The total follow-up duration is 90 days.

Study Timeline

• Study First Submitted: 2025-02-20
• Study First Submitted QC: 2025-02-22
• Status Verified: 2025-03
• Study Start: 2025-03
• Study First Posted: 2025-03-25
• Last Update Submitted: 2025-03-25
• Last Update Posted: 2025-03-28
• Primary Completion: 2026-12
• Study Completion: 2027-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 1204

Inclusion Criteria

1. Age ≥18 years.
2. Having anterior circulation AIS within 24 hours of onset.
3. The NIHSS score at enrollment is 4 to 25.
4. Receiving intravenous recombinant tissue plasminogen activator (rt-PA) or TNK-tPA, or endovascular treatment including intra-arterial thrombolysis, mechanical thrombectomy, or intravenous rt-PA /TNK-tPA bridging endovascular treatment.
5. Being independent in daily activities (mRS ≤1) before onset.
6. Patients or their legal representatives are able and willing to sign informed consent forms.

Exclusion Criteria

1. Having an Alberta Stroke Program Early Computed Tomography Score (ASPECT) score of 6 or less confirmed by preoperational computed tomography scan.
2. Being already treated with HUK or any drugs containing HUK after onset.
3. Having an allergy history of HUK or drugs containing HUK, or other drugs and food.
4. Having a history of coagulation dysfunction, systemic bleeding, or thrombocytopenia; having hemorrhagic diseases at the time of enrollment, including cerebral hemorrhage, subarachnoid hemorrhage, epidural or subdural hematoma, gingival bleeding, gastrointestinal bleeding, dermal ecchymosis, etc; taking anticoagulants including warfarin, rivaroxaban, etc.; or taking heparin within 48 hours after stroke onset.
5. Taking angiotensin-converting enzyme inhibitor (ACEI) antihypertensive drugs regularly within one week before enrollment, including captopril, enalapril, benazepril, etc.
6. Having chronic liver disease or liver dysfunction, with elevated ALT/AST (>3.0×ULN ); or having kidney dysfunction or receiving dialysis, with elevated serum creatinine (>2.0×ULN).
7. Having severe cardiopulmonary disease that are deemed unsuitable for the study by the investigators.
8. Having contraindications for intravenous thrombolysis or endovascular treatment, including intra-arterial thrombolysis, mechanical thrombectomy, or intravenous rt-PA /TNK-tPA bridging endovascular treatment.
9. Having lethal diseases with a life expectancy < 3 months.
10. Being pregnant or lactating; or women of child-bearing age not taking effective contraception, or having no negative pregnancy test record.
11. Being unable to complete the study due to mental illness, cognitive or emotional disorder, physical condition, geographical factors, etc.
12. Participating in another clinical trial currently.
13. Other conditions that investigators consider he/she is not appropriate to participate in this study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Intervention group	Human urinary kallidinogenase (HUK)	HUK (0.15 PNA) and sodium chloride injection (100ml), once per day
Control group	Placebo	placebo (0 PNA) and sodium chloride injection (100ml), once per day

Primary Outcome Measures

Name	Time	Method
Proportion of a favorable outcome (mRS 0-2)	at 90 days	The proportion of a favorable outcome, defined by a modified Rankin Scale (mRS) score ranging from 0 to 2, reflects the percentage of patients who attained a functional status from no symptoms to mild disability, enabling them to perform all pre-stroke activities without assistance.

Secondary Outcome Measures

Name	Time	Method
Proportion of a favorable outcome (mRS 0-2)	at 14 days	The proportion of a favorable outcome, defined by a modified Rankin Scale (mRS) score ranging from 0 to 2, reflects the percentage of patients who attained a functional status from no symptoms to mild disability, enabling them to perform all pre-stroke activities without assistance.
Proportion of an excellent outcome (mRS 0-1)	at 90 days	The proportion of an excellent outcome, characterized by a modified Rankin Scale (mRS) score of 0 to 1, represents the percentage of patients who achieved a functional status from no symptoms to no significant disability despite symptoms, allowing them to resume all pre-stroke activities without any aid.
Distribution of mRS score	at 90 days	The distribution of modified Rankin Scale (mRS) scores provides a comprehensive overview of the functional outcomes across a patient population, categorizing the degree of disability from no symptoms (score 0) to severe disability or death (score 6).
Improvement of NIHSS score	at 14 days	The improvement of the National Institutes of Health Stroke Scale (NIHSS) score serves as a quantifiable measure of neurological recovery, reflecting the reduction in stroke-related deficits and the enhancement of patient functional capabilities over time. Minimum Score: 0 (no stroke symptoms) Maximum Score: 42 (severe stroke) Higher NIHSS scores indicate more severe stroke symptoms and are associated with worse outcomes.Lower NIHSS scores indicate milder stroke symptoms and are associated with better outcomes.
Risk of recurrent symptomatic stroke	within 90 days	The risk of recurrent symptomatic stroke quantifies the probability of a subsequent stroke event with clinical manifestations, providing a critical measure for assessing the long-term efficacy of stroke prevention strategies and the ongoing vulnerability of the patient population.
Risk of recurrent symptomatic ischemic stroke	within 90 days	The risk of recurrent symptomatic ischemic stroke delineates the likelihood of a subsequent ischemic stroke event accompanied by clinical symptoms, serving as a pivotal indicator for evaluating the effectiveness of secondary prevention measures and the persistent threat of cerebral ischemia in affected individuals.
Risk of combined vascular events	within 90 days	The risk of combined vascular events encompasses the probability of experiencing any major vascular incident, such as stroke, myocardial infarction, or vascular death, offering a comprehensive metric for assessing the overall burden of vascular disease and the aggregate impact of therapeutic interventions on cardiovascular health.
Improvement of EQ-5D-5L	at 90 days	The improvement of EQ-5D-5L(EuroQol 5-Dimension 5-Level) reflects an enhancement in health-related quality of life, as measured by gains across five dimensions-mobility, self-care, usual activities, pain/discomfort, and anxiety/depression-on a five-level severity scale, indicating a positive shift in the patient's overall health state and well-being.; Minimum Score: 0 (worst imaginable health state) Maximum Score: 100 (best imaginable health state) For the descriptive system, a lower score (closer to 11111) indicates better health-related quality of life, while a higher score (closer to 55555) indicates worse health-related quality of life.; For the VAS, a higher score (closer to 100) indicates better self-rated health, while a lower score (closer to 0) indicates worse self-rated health.
Improvement of MOCA	at 90 days	The improvement of the Montreal Cognitive Assessment (MoCA) score signifies an enhancement in cognitive function, encompassing domains such as attention, memory, language, and executive functions, thereby indicating a positive progression in the patient's cognitive status and potential recovery from cognitive impairment.; Minimum Score: 0 (severe cognitive impairment) Maximum Score: 30 (no cognitive impairment) Higher MoCA scores indicate better cognitive function. Lower MoCA scores indicate worse cognitive function.

Trial Locations

Locations (1)

Beijing Tiantan Hospital, Capital Medical University; 🇨🇳 Beijing, Beijing, China