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

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.

Study Overview

• Status: Recruiting
• Conditions: Acute Ischemic Stroke
• Intervention / Treatment: Drug: Human urinary kallidinogenase (HUK); Drug: Placebo

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 Type: Interventional
• Enrollment (Estimated): 1204
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Wang Yilong, MD, PhD; Phone Number: 0086-010-59976274; Email: yilong528@aliyun.com
• Study Contact Backup: Name: Wang Tingting, MD; Phone Number: 0086-18810956596; Email: wangtingtingdr@sina.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100070
      • Recruiting
      • Beijing Tiantan Hospital, Capital Medical University
      • Contact: Wang Yilong, MD, PhD; Phone Number: 0086-010-59976274; Email: yilong528@aliyun.com
      • Contact: Wang Tingting, MD; Phone Number: 0086-18810956596; Email: wangtingtingdr@sina.com
      • Principal Investigator: Wang Yilong, MD, PhD
      • Sub-Investigator: Wang Tingting, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention group; HUK (0.15 PNA) and sodium chloride injection (100ml), once per day	Drug: Human urinary kallidinogenase (HUK); HUK (0.15 PNA) and sodium chloride injection (100ml), once per day
Placebo Comparator: Control group; placebo (0 PNA) and sodium chloride injection (100ml), once per day	Drug: Placebo; placebo (0 PNA) and sodium chloride injection (100ml), once per day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of a favorable outcome (mRS 0-2)	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.	at 90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of a favorable outcome (mRS 0-2)	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.	at 14 days
Proportion of an excellent outcome (mRS 0-1)	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.	at 90 days
Distribution of mRS score	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).	at 90 days
Improvement of NIHSS score	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.	at 14 days
Risk of recurrent symptomatic stroke	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.	within 90 days
Risk of recurrent symptomatic ischemic stroke	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.	within 90 days
Risk of combined vascular events	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.	within 90 days
Improvement of EQ-5D-5L	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.	at 90 days
Improvement of MOCA	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.	at 90 days

Collaborators and Investigators

• Sponsor: Beijing Tiantan Hospital
• Investigators: Study Chair: Wang Yilong, MD, PhD, Beijing Tiantan Hospital; Study Director: Wang Tingting, MD, Beijing Tiantan Hospital

Publications and helpful links

General Publications

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Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: February 20, 2025
• First Submitted That Met QC Criteria: February 22, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 28, 2025
• Last Update Submitted That Met QC Criteria: March 25, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Acute Ischemic Stroke; Human Urinary Kallidinogenase; Reperfusion Treatment
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Brain Infarction; Brain Ischemia; Infarction; Necrosis; Ischemic Stroke; Stroke; Cerebral Infarction; Ischemia; Physiological Effects of Drugs; Coagulants; Reproductive Control Agents; Fertility Agents; Fertility Agents, Male; Kallikreins
• Other Study ID Numbers: KY2024-320-04

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No