Acute Ischemic Stroke, rhTNK-tPA
Conditions
Keywords
Acute Ischemic Stroke, rhTNK-tPA
Brief summary
This is a multicenter, prospective, non-randomized, post-marketing safety surveillance cohort study with rt-PA (Actilyse®) as the control. It is designed to evaluate the safety of intravenous thrombolysis with recombinant human TNK tissue-type plasminogen activator (rhTNK-tPA, Mingfule®) compared with rt-PA (Actilyse®) in patients with acute ischemic stroke in the real-world setting. This is a non-interventional observational study with no randomization. Treatment decisions are made by treating physicians based on routine clinical practice and the patient's condition. Patients are naturally allocated to the rhTNK-tPA group or the rt-PA group according to the actual thrombolytic drug they receive.
Detailed description
This is a multicenter, prospective, non-randomized, parallel-group, post-marketing safety surveillance cohort study conducted in routine clinical practice to compare the safety of intravenous thrombolysis with rhTNK-tPA (Mingfule®) versus rt-PA (Actilyse®) in patients with acute ischemic stroke. As a non-interventional observational study, no randomization or blinding is applied. The choice of thrombolytic agent is determined solely by the treating physician in accordance with clinical guidelines and individual patient circumstances. Patients are assigned to one of two groups based on the actual treatment received: rhTNK-tPA group: Administered 0.25 mg/kg (maximum 25 mg) as a single intravenous bolus injection per the approved package insert. rt-PA group: Administered 0.9 mg/kg per the approved package insert, with 10% of the total dose given as an intravenous bolus and the remaining 90% infused continuously over 60 minutes. The target sample size is approximately 4,500 patients, with about 3,000 in the rhTNK-tPA group and at least 1,500 in the rt-PA group. This sample size is selected to fulfill the regulatory requirements for post-marketing intensive monitoring and to ensure sufficient statistical precision for safety comparisons between the two treatment groups.
Interventions
DRUGrhTNK-tPA
The rhTNK-tPA (Mingfule®) is administered as an intravenous bolus injection at a dose of 0.25 mg/kg, with a maximum dose of 25 mg, in accordance with the approved package insert.
DRUGrt-PA
The rt-PA (Actilyse®) is administered intravenously at a dose of 0.9 mg/kg. The 10% of total dose is given as an intravenous bolus, and the remaining 90% is infused continuously over 60 minutes, in accordance with the approved package insert.
Sponsors
CSPC Mingfule Pharmaceutical (Guangzhou) Co., Ltd.
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Adult patients aged 18 years or older. 2. Time from symptom onset to treatment \< 4.5 hours, with the time of symptom onset defined as "last known normal time". 3. Meet the diagnostic criteria for acute ischemic stroke, confirmed by imaging (head CT or MRI). 4. Baseline National Institutes of Health Stroke Scale (NIHSS) score ≤ 25 points at admission. 5. Planned to receive intravenous thrombolysis with either rhTNK-tPA (Mingfule®) 0.25 mg/kg or rt-PA (Actilyse®) 0.9 mg/kg. 6. Voluntary signing of the informed consent form by the participant or their legal guardian. 7. Have complete clinical and imaging data, and be able to cooperate with follow-up assessments.
Exclusion criteria
1. Patients with absolute contraindications to reperfusion therapy (including intravenous thrombolysis and mechanical thrombectomy), specifically: Intracranial hemorrhage (including parenchymal hemorrhage, intraventricular hemorrhage, subarachnoid hemorrhage, subdural/epidural hematoma, etc.) History of prior intracranial hemorrhage Severe head trauma or stroke within the past 3 months Intracranial tumor or giant intracranial aneurysm Intracranial or intraspinal surgery within the past 3 months Major surgical procedure within the past 2 weeks Gastrointestinal or urinary tract bleeding within the past 3 weeks Active visceral bleeding Aortic arch dissection Arterial puncture at a non-compressible site within the past 1 week 11 Elevated blood pressure: systolic blood pressure ≥ 180 mmHg or diastolic blood pressure ≥ 100 mmHg 12 Acute bleeding diathesis, including platelet count \< 100×10⁹/L or other conditions 13 Treatment with low molecular weight heparin within the past 24 hours 14 Oral anticoagulant use (warfarin) with INR \> 1.7 or PT \> 15 seconds 15 Use of thrombin inhibitors or factor Xa inhibitors within the past 48 hours, or abnormal laboratory tests deemed by the investigator to contraindicate thrombolysis (e.g., APTT, INR, platelet count, ECT, TT, or factor Xa activity assay) 16 Random blood glucose \< 2.8 mmol/L or \> 22.22 mmol/L 17 Head CT or MRI showing large-area infarction (infarct volume \> 1/3 of the middle cerebral artery territory) 2. Known pregnant or lactating female patients (judged by the investigator based on last menstrual period, medical history, or patient/family report). 3. Patients who have received prior reperfusion therapy outside the hospital (including intravenous thrombolysis and endovascular treatment). 4. Patients expected to be unable to complete follow-up (e.g., predicted survival \< 3 months, or inability to comply with follow-up plans for other reasons). 5. Patients participating in other clinical trials where the interventions may affect the results of this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of symptomatic intracerebral hemorrhage (defined according to the ECASS III criteria) within 36 hours after thrombolysis treatment | Within 36 hours after thrombolysis treatment | Defined by ECASS III: any intraparenchymal or intracranial hemorrhage associated with clinical deterioration, where the latter is defined as an increase of ≥4 points in the National Institutes of Health Stroke Scale \[NIHSS\] score or death, with confirmation that the hemorrhage is the cause of neurological deterioration. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall mortality rate at Day 90. | At Day 90 | The proportion of randomized patients who died within 90 days |
| Proportion of adverse drug reactions (ADRs) at Day 90. | At Day 90 | An adverse drug reactions (ADR) refers to any untoward medical occurrence that is judged to be causally related to the use of the study drug. All adverse events related to drug overdose or medication error shall be regarded as ADRs |
| Proportion of serious adverse events (SAEs) at Day 90. | At Day 90 | A Serious Adverse Event (SAE) refers to a special safety event among AEs that meets any of the following criteria: "resulting in death, life-threatening, requiring hospitalization/prolongation of existing hospitalization, causing permanent or severe disability/incapacity, leading to congenital anomalies/birth defects, or being another important medical event. |
| Incidence of stroke recurrence at Day 90. | At Day 90 | Percentage of participants experiencing a new or worsening acute ischemic stroke event occurring after initial thrombolysis treatment through Day 90. |
| Time to stroke recurrence | At Day 90 | The time interval from the start of thrombolysis treatment to the first occurrence of stroke recurrence within 90 days. |
Contacts
CONTACTClinical Trials Information Group officer
PRINCIPAL_INVESTIGATORYongjun Wang, MD
Beijing Tiantan Hospital
Outcome results
None listed