Efficacy and Safety of Human Urinary Kallidinogenase Combined With Reteplase Intravenous Thrombolysis in the Treatment of Acute Ischemic Stroke

Overview

This study is a multicentre, randomized, blinded-endpoint trial that aims to evaluate the efficacy and safety of human urinary kallidinogenase combined with reteplase intravenous thrombolysis in the treatment of acute ischemic stroke

Detailed description

Reteplase intravenous thrombolysis for acute ischemic stroke (AIS) owing to a prolonged half-life and bolus dosing. However, some patients still do not achieve favorable outcomes, likely due to complex pathophysiological processes such as oxidative stress, inflammation, and apoptosis triggered after stroke. Human urinary kallidinogenase primarily acts through the kallikrein-kinin system (KKS). It can improve oxygen supply to ischemic brain tissue, promote the establishment of collateral circulation, alleviate ischemic reperfusion injury, and exert anti-inflammatory and antioxidant effects. Whether its combination with reteplase can further improve neurological recovery in patients without increasing the risk of hemorrhage remains unreported. Therefore, this study aims to investigate the efficacy and safety of combining human urinary kallidinogenase with reteplase in the treatment of AIS.

Interventions

• Drug Human Urinary Kallidinogenase
  Intravenous injections of urinary kallidinogenase (0.15 PNA units) dissolved in 100 ml of normal saline, administered via slow intravenous drip over no less than 50 minutes,once a day. The solvent can be increased and/or slowed down according to the patient's condition for 8±1 days
• Other Clinical Routine Treatment
  Conventional therapy of acute ischemic stroke after based on Chinese guidelines

Primary outcome measures

• Proportion of patients with modified Rankin Scale (mRS) 0-1 [Time frame: 90 days]

Secondary outcome measures (8)

• ordinal distribution of modified Rankin Scale (mRS) [Time frame: 90 days]
• Proportion of patients with modified Rankin Scale (mRS) 0-2 [Time frame: 90 days]
• occurrence of early neurological improvement (ENI) [Time frame: 24 、24-48 hours]
• change of National Institute of Health stroke scale (NIHSS) score [Time frame: 24 、24-48 hours]
• change in National Institute of Health stroke scale (NIHSS) score [Time frame: 8±1 days]
• Changes of Barthel index from baseline [Time frame: 90 days]
• Proportion of patients with Barthel Index (BI) ≥ 95 [Time frame: 90 days]
• Stroke recurrence rate [Time frame: 90 days]

Eligibility criteria

Inclusion criteria

• Meet the diagnostic criteria of the Chinese Guidelines for the Diagnosis and Treatment of Acute Ischemic Stroke 2023
• Age ≥ 18 years
• The time from last known well to treatment is within 4.5 hours
• First-ever ischemic stroke or have history of ischemic stroke but mRS≤1 before onset
• 6 ≤NIHSS≤ 16
• Meet the clinical thrombolysis indications in the Chinese Guidelines for the Diagnosis and Treatment of Ischemic Stroke and receive reteplase intravenous thrombolysis
• Have provided signed written informed consent from the patient or the patient's legal representative

Exclusion criteria

• Preoperative non-contrast head CT shows Alberta Stroke Program Early CT Score (ASPECTS) ≤ 6
• Presence of contraindications to intravenous thrombolysis
• Patients who have been on angiotensin-converting enzyme inhibitor (ACEI) drugs and within 5 half-lives (according to the specific drug instructions) before initiate Human Urinary Kallidinogenase treatment
• Planed for endovascular treatment
• Patients with fracture, claudication and other factors affecting functional outcome score upon admission
• Use of Edaravone Injection, Edaravone Dexborneol Injection, Sublingual Edaravone Dexborneol, Butylphthalide Injection or Capsules after the onset of the current episode
• Severe uncontrolled hypertension: systolic blood pressure ≥ 180 mmHg or diastolic blood pressure ≥ 110 mmHg
• History of severe food or drug allergies, or prior allergy or intolerance to urinary kallidinogenase for injection
• Pregnant or lactating women, or patients planning pregnancy within 90 days
• Renal failure or severe renal impairment (creatinine clearance < 30 mL/min) at screening
• Liver function impairment: Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2.5 times the upper limit of normal, or liver diseases (e.g., acute/chronic hepatitis, cirrhosis)
• Heart failure (NYHA Class III or IV), unstable angina, acute myocardial infarction, severe arrhythmia, or second/third-degree cardiac conduction obstruction within 6 months before randomization
• Drug abuse or addiction in the past year
• Concurrent malignant tumors or severe systemic diseases with an expected survival < 90 days
• Severe mental disorders or dementia unable to complete the informed consent and follow-up
• Participation in any interventional drug or device clinical trial within 3 months before screening
• Patients deemed unsuitable for the study by the investigator

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

China · 1 center

• China-Japan Union Hospital of Jilin University — Changchun

Identifiers

NCT: NCT07483281 · KLK-S029

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗