Observational Study to Assess the Safety of rhTNK-tPA (Mingfule®) vs. Rt-PA (Actilyse®) in Treating Acute Ischemic Stroke

A Multicenter, Prospective, Non-Randomized, Parallel-Group, Post-Marketing Observational Patient Registry Study to Evaluate the Safety of Intravenous Thrombolysis With Recombinant Human TNK Tissue-Type Plasminogen Activator for Injection (rhTNK-tPA, Mingfule®) Compared With Recombinant Tissue Plasminogen Activator (Rt-PA, Actilyse®) in Patients With Acute Ischemic Stroke

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Acute Ischemic Stroke; rhTNK-tPA
• Intervention / Treatment: Drug: rhTNK-tPA; Drug: rt-PA

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.

• Study Type: Observational
• Enrollment (Estimated): 4500

Contacts and Locations

• Study Contact: Name: Clinical Trials Information Group officer; Phone Number: 031169085587; Email: ctr-contact@cspc.cn

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

The study population consists of adult patients diagnosed with acute ischemic stroke (AIS) who present to the emergency departments or stroke centers of participating hospitals in China. This cohort includes individuals who are eligible for intravenous thrombolysis (IVT) within the standard therapeutic time window and are treated with rhTNK-tPA or rt-PA in a real-world clinical setting.

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
rhTNK-tPA group	Drug: rhTNK-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.
rt-PA group	Drug: rt-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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of symptomatic intracerebral hemorrhage (defined according to the ECASS III criteria) 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.	Within 36 hours after thrombolysis treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall mortality rate at Day 90.	The proportion of randomized patients who died within 90 days	At Day 90
Proportion of adverse drug reactions (ADRs) 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	At Day 90
Proportion of serious adverse events (SAEs) 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.	At Day 90
Incidence of stroke recurrence at Day 90.	Percentage of participants experiencing a new or worsening acute ischemic stroke event occurring after initial thrombolysis treatment through Day 90.	At Day 90
Time to stroke recurrence	The time interval from the start of thrombolysis treatment to the first occurrence of stroke recurrence within 90 days.	At Day 90

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants with mRS score of 0-1 at Day 90.	The modified Rankin Scale (mRS) is used to assess the status of neurological function recovery in patients after stroke. By evaluating the independence of patients in daily activities, it classifies functional levels into grades 0-6 (Grade 0 indicates no symptoms at all, Grades 1-5 correspond to functional impairments ranging from mild to severe, and Grade 6 indicates death).	At Day 90
Proportion of participants with mRS score of 0-2 at Day 90.	The modified Rankin Scale (mRS) is used to assess the status of neurological function recovery in patients after stroke. By evaluating the independence of patients in daily activities, it classifies functional levels into grades 0-6 (Grade 0 indicates no symptoms at all, Grades 1-5 correspond to functional impairments ranging from mild to severe, and Grade 6 indicates death).	At Day 90
The full ordinal distribution of Modified Rankin Scale (mRS) score at Day 90.	The modified Rankin Scale (mRS) is used to assess the status of neurological function recovery in patients after stroke. By evaluating the independence of patients in daily activities, it classifies functional levels into grades 0-6 (Grade 0 indicates no symptoms at all, Grades 1-5 correspond to functional impairments ranging from mild to severe, and Grade 6 indicates death).	At Day 90

Collaborators and Investigators

• Sponsor: CSPC Mingfule Pharmaceutical (Guangzhou) Co., Ltd.
• Investigators: Principal Investigator: Yongjun Wang, MD, Beijing Tiantan Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): April 10, 2026
• Primary Completion (Estimated): January 10, 2027
• Study Completion (Estimated): April 10, 2027

Study Registration Dates

• First Submitted: March 27, 2026
• First Submitted That Met QC Criteria: April 6, 2026
• First Posted (Actual): April 9, 2026

Study Record Updates

• Last Update Posted (Actual): April 9, 2026
• Last Update Submitted That Met QC Criteria: April 6, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Acute Ischemic Stroke; rhTNK-tPA
• 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: MK02-004

Drug and device information, study documents

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