Acute Ischemic Stroke
Conditions
Keywords
Acute Ischemic Stroke, Human Urinary Kallidinogenase, KLK, Reteplase, HUK, Intravenous Thrombolysis
Brief summary
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
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
Conventional therapy of acute ischemic stroke after based on Chinese guidelines
Sponsors
China-Japan Union Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Meet the diagnostic criteria of the Chinese Guidelines for the Diagnosis and Treatment of Acute Ischemic Stroke 2023 2. Age ≥ 18 years 3. The time from last known well to treatment is within 4.5 hours 4. First-ever ischemic stroke or have history of ischemic stroke but mRS≤1 before onset 5. 6 ≤NIHSS≤ 16 6. Meet the clinical thrombolysis indications in the Chinese Guidelines for the Diagnosis and Treatment of Ischemic Stroke and receive reteplase intravenous thrombolysis 7. Have provided signed written informed consent from the patient or the patient's legal representative
Exclusion criteria
1. Preoperative non-contrast head CT shows Alberta Stroke Program Early CT Score (ASPECTS) ≤ 6 2. Presence of contraindications to intravenous thrombolysis 3. 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 4. Planed for endovascular treatment 5. Patients with fracture, claudication and other factors affecting functional outcome score upon admission 6. Use of Edaravone Injection, Edaravone Dexborneol Injection, Sublingual Edaravone Dexborneol, Butylphthalide Injection or Capsules after the onset of the current episode 7. Severe uncontrolled hypertension: systolic blood pressure ≥ 180 mmHg or diastolic blood pressure ≥ 110 mmHg 8. History of severe food or drug allergies, or prior allergy or intolerance to urinary kallidinogenase for injection 9. Pregnant or lactating women, or patients planning pregnancy within 90 days 10. Renal failure or severe renal impairment (creatinine clearance \< 30 mL/min) at screening 11. 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) 12. 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 13. Drug abuse or addiction in the past year 14. Concurrent malignant tumors or severe systemic diseases with an expected survival \< 90 days 15. Severe mental disorders or dementia unable to complete the informed consent and follow-up 16. Participation in any interventional drug or device clinical trial within 3 months before screening 17. Patients deemed unsuitable for the study by the investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of patients with modified Rankin Scale (mRS) 0-1 | 90 days | mRS scores range from 0 to 6. 0=no symptoms,1 = symptoms without clinically significant disability,2 = slight disability,3 = moderate disability,4 = moderately severe disability,5 = severe disability; and 6 = death |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ordinal distribution of modified Rankin Scale (mRS) | 90 days | The minimum and maximum values of mRS are 0 and 6, respectively; higher score mean a worse outcome |
| Proportion of patients with modified Rankin Scale (mRS) 0-2 | 90 days | The minimum and maximum values of mRS are 0 and 6, respectively; higher score mean a worse outcome |
| occurrence of early neurological improvement (ENI) | 24 、24-48 hours | ENI is defined as more than 4-point decrease in National Institute of Health stroke scale score or NIHSS score ≤ 1 |
| change of National Institute of Health stroke scale (NIHSS) score | 24 、24-48 hours | NIHSS ranges from 0 to 42, a low value represents a better outcome |
| change in National Institute of Health stroke scale (NIHSS) score | 8±1 days | NIHSS ranges from 0 to 42, a low value represents a better outcome |
| Changes of Barthel index from baseline | 90 days | Barthel Index is used to assess patients' activities of daily living (ADL), with a total score of 100 points. A higher score indicates better self-care ability |
| Proportion of patients with Barthel Index (BI) ≥ 95 | 90 days | Barthel Index is used to assess patients' activities of daily living (ADL), with a total score of 100 points. A higher score indicates better self-care ability |
| Stroke recurrence rate | 90 days | Stroke recurrence rate within 90 days |
Countries
China
Contacts
CONTACTGuangxian Nan, MD, Ph.D
CONTACTLumei Chi
Outcome results
None listed