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

Обзор

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

Подробное описание

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.

Вмешательства

• Препарат 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
• Другое Clinical Routine Treatment
  Conventional therapy of acute ischemic stroke after based on Chinese guidelines

Первичные конечные точки

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

Вторичные конечные точки (8)

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

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Простое слепое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• China-Japan Union Hospital of Jilin University — Changchun

Идентификаторы

NCT: NCT07483281 · KLK-S029

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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