Tenecteplase Plus Urinary Kallidinogenase for Acute Ischemic Stroke (TUKIS)

Tenecteplase Plus Urinary Kallidinogenase for Acute Ischemic Stroke (TUKIS): a Prospective, Randomized, Double Blinded and Multi-center Study

Human urinary kallidinogenase (HUK) is a tissue kallikrein extracted from human urine. Under certain conditions, tissue kallikrein can convert kininogen into kallidin and kinins, thereby promoting vascular endothelial function, and exerting anti-inflammatory and antioxidant effects. Preclinical and clinical studies have demonstrated that HUK can salvage the ischemic penumbra and significantly promote the establishment of collateral circulation. Existing research suggests that the combination of HUK with intravenous alteplase significantly improves neurological function in patients with acute ischemic stroke (AIS) without increasing the risk of hemorrhage. However, whether its combination with tenecteplase can further enhance neurological recovery in patients remains unreported. Based on the above discussion, this study aims to investigate the efficacy and safety of combining tenecteplase with HUK in the treatment of AIS.

Study Overview

• Status: Recruiting
• Conditions: Ischemic Stroke
• Intervention / Treatment: Drug: Human Urinary Kallidinogenase

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Shenyang, China, 110016
    • Recruiting
    • Department of Neurology, General Hospital of Northern Theater Command
    • Contact: Hui-Sheng Chen, Ph.D.; Phone Number: +86 13352452086; Email: chszh@aliyun.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age ≥ 18 year;
• Acute ischemic stroke confirmed by neuroimaging;
• The time from last known well to treatment is within 4.5 hours;
• NIHSS ≥ 6 at randomization;
• Received intravenous tenecteplase (0.25mg/kg);
• First stroke onset or past stroke without obvious neurological deficit (mRS≤1);
• Signed informed consent.

Exclusion Criteria:

• Planed for endovascular treatment;
• Use of Edaravone Injection, Edaravone Dexborneol Injection, Butylphthalide Injection or Capsules after the onset of the current episode；
• Prior use of ACE inhibitors within a period less than 5 half-lives before the intended administration of Urinary Kallidinogenase for Injection；
• Pregnancy；
• Allergy to the investigational drug(s)；
• Comorbidity with other serious diseases;
• Participating in other clinical trials within 3 months;
• Patients not suitable for the study considered by researcher.

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: experimental group; Urinary Kallidinogenase with 0.15 PNA units dissolved in 100 ml of normal saline, administered via slow intravenous drip over no less than 50 minutes, once daily	Drug: Human Urinary Kallidinogenase; Human Urinary Kallidinogenase is administered intravenously, with 0.15 PNA units dissolved in 100 ml of normal saline.
Placebo Comparator: Control group; Urinary Kallidinogenase with placebo dissolved in 100 ml of normal saline, administered via slow intravenous drip over no less than 50 minutes, once daily	Drug: Human Urinary Kallidinogenase; Human Urinary Kallidinogenase is administered intravenously, with 0.15 PNA units dissolved in 100 ml of normal saline.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
proportion of excellent functional outcome (modified Rankin Scale (mRS) 0-1)	The minimum and maximum values of mRS are 0 and 6, respectively; higher score mean a worse outcome	90±7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
proportion of modified Rankin Scale (mRS) 0-2	The minimum and maximum values of mRS are 0 and 6, respectively; higher score mean a worse outcome	90±7 days
ordinal distribution of modified Rankin Scale (mRS)	The minimum and maximum values of mRS are 0 and 6, respectively; higher score mean a worse outcome	90±7 days
occurrence of early neurological improvement (ENI)	ENI is defined as more than 4-point decrease in National Institute of Health stroke scale score	24 (-6/+12) hours
new stroke or other vascular event(s)		90±7 days
change in National Institute of Health stroke scale (NIHSS) score	the minimum and maximum values of NIHSS are 0 and 42, respectively; higher NIHSS mean a worse outcome	24 (-6/+12) hours
change in National Institute of Health stroke scale (NIHSS) score	the minimum and maximum values of NIHSS are 0 and 42, respectively; higher NIHSS mean a worse outcome	10±2 days
symptomatic intracranial hemorrhage (sICH)	sICH was defined as any evidence of bleeding on the head computed tomographic scan associated with clinically significant neurological deterioration (≥4-point increase in NIHSS score).	24 (-6/+12) hours
major systemic bleeding events	Bleeding leading to a decrease in hemoglobin ≥ 2 g/dL or transfusion of ≥ 2 units of blood.	24 (-6/+12) hours
any bleeding events	Including skin and mucosal bleeding, gingival bleeding, bleeding at other organ sites, and other types of hemorrhage.	24 (-6/+12) hours
any intracranial hemorrhage	Heidelberg Bleeding Classification	10±2 days
all-cause mortality	death from any cause	90±7 days

Collaborators and Investigators

• Sponsor: General Hospital of Shenyang Military Region

Study record dates

Study Major Dates

• Study Start (Actual): January 20, 2026
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): December 30, 2027

Study Registration Dates

• First Submitted: December 2, 2025
• First Submitted That Met QC Criteria: December 2, 2025
• First Posted (Actual): December 15, 2025

Study Record Updates

• Last Update Posted (Actual): January 23, 2026
• Last Update Submitted That Met QC Criteria: January 22, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Stroke; Ischemic Stroke
• Other Study ID Numbers: Y (2025) 357

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No