## Protocol Section
### Identification Module
**NCT ID:** NCT06414499

**Brief Title:** Teneteplase Reperfusion Therapy in Acute Ischemic Cerebrovascular Events-Ⅳ(TRACE Ⅳ)

**Official Title:** TNK-tPA Treatment for Acute Minor Ischemic Stroke：A Multicenter, Prospective, Open Label, Blinded-endpoint, Randomized Controlled Trial

#### Organization Study ID Info
**ID:** NCRC-2024-03
#### Organization
**Class:** OTHER
**Full Name:** Beijing Tiantan Hospital
### Status Module
#### Completion Date
**Date:** 2025-12-31

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-16

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-10

**Overall Status:** RECRUITING

#### Primary Completion Date
**Date:** 2025-07-31

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-05-20

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-16
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-10
**Study First Submit QC Date:** 2024-05-10
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Beijing Tiantan Hospital

#### Responsible Party

**Investigator Affiliation:** Beijing Tiantan Hospital

**Investigator Full Name:** Yongjun Wang

**Investigator Title:** professor

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** True

### Description Module

**Brief Summary:** The trial is a multicenter, prospective, open-label, blinded-endpoint randomized controlled design. Participants with acute minor ischemic stroke (baseline NIHSS≤5) accompanied with measurable neurological deficit will be randomized 1:1 to 0.25mg/kg intravenous tenecteplase or standard medical treatment.

**Detailed Description:** The study will be a multicenter, prospective, open-label, blinded-endpoint randomized controlled trial (2 arms with 1:1 randomization). Participants with acute minor ischemic stroke (baseline NIHSS≤5) within 4.5 hours of symptoms onset (symptom onset is defined by the "last seen normal" principle for wake-up stroke) accompanied with measurable neurological deficit will be enrolled. The measurable neurological deficit is defined as impairment of language or motor function. Participants will be randomized into 2 groups: Intervention group (rhTNK-tPA): 0.25mg/kg, the maximum dose does not exceed 25mg. Control group (standard medical care): Single/dual antiplatelet therapy (aspirin, clopidogrel, ticagrelor, etc.) according to the guideline. The primary endpoint is excellent functional outcome (Modified Rankin Scale score, mRS 0-1) at 90-day.

### Conditions Module

**Conditions:**

- Tenecteplase

- Minor Ischemic Stroke

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** SINGLE

**Who Masked:**

- OUTCOMES_ASSESSOR

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 1874

**Type:** ESTIMATED

**Phases:**

- PHASE3

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Within 4.5 hours of symptom onset:

Intervention group (rhTNK-tPA): 0.25mg/kg, the maximum dose does not exceed 25mg: 1 vial is dissolved in 3ml of sterile water for injection to prepare a medicinal solution with a concentration of 5.33mg/ml. Calculate the total amount of the drug according to the weight of participant, and the maximum dose shall not exceed 25 mg. It is administered as a single bolus intravenous injection, and the injection is completed within 5-10 seconds.

**Intervention Names:**

- Drug: rhTNK-tPA

**Label:** rhTNK-tPA

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** Within 4.5 hours of symptom onset:

Control group (standard medical care): Single/dual antiplatelet therapy (aspirin, clopidogrel, ticagrelor, etc.) according to the guideline.

**Intervention Names:**

- Drug: Single/dual antiplatelet therapy

**Label:** Standard medical care

**Type:** PLACEBO_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- rhTNK-tPA

**Description:** 0.25mg/kg, the maximum dose does not exceed 25mg: 1 vial is dissolved in 3ml of sterile water for injection to prepare a medicinal solution with a concentration of 5.33mg/ml. Calculate the total amount of the drug according to the weight of participant, and the maximum dose shall not exceed 25 mg. It is administered as a single bolus intravenous injection, and the injection is completed within 5-10 seconds.

**Name:** rhTNK-tPA

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- Standard medical care

**Description:** Single/dual antiplatelet therapy (aspirin, clopidogrel, ticagrelor, etc.) according to the guideline.

**Name:** Single/dual antiplatelet therapy

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** Modified Rankin Scale score, mRS 0-1

**Measure:** Excellent functional outcome (Modified Rankin Scale score, mRS 0-1) at 90-day (± 7 days).

**Time Frame:** at 90-day (± 7 days)

#### Secondary Outcomes

**Measure:** Good functional outcome (mRS 0-2) at 90-day (± 7 days)

**Time Frame:** at 90-day (± 7 days)

**Measure:** Ordinal distribution of mRS scores at 90-day (± 7 days)

**Time Frame:** at 90-day (± 7 days)

**Measure:** NIHSS 0-1 at 24-hour, 7-day or discharge (analyze which occurs first) or/ neurological improvement (NIHSS decreased≥2 from baseline)

**Time Frame:** at 24-hour, 7-day or discharge (analyze which occurs first)

**Measure:** Neurological impairment (NIHSS increased≥4 from baseline) at 90-day (± 7 days)

**Time Frame:** at 90-day (± 7 days)

**Measure:** New clinical vascular events (ischemic stroke/ hemorrhagic stroke/ myocardial infarction/vascular death) at 90-day (± 7 days), with each vascular event being independently evaluated.

**Time Frame:** at 90-day (± 7 days)

**Measure:** Symptomatic intracranial hemorrhage according to the ECASSIII criteria at 36-hour, 7-day or discharge (analyze which occurs first).

**Time Frame:** at 36-hour, 7-day or discharge (analyze which occurs first)

**Measure:** Symptomatic intracranial hemorrhage according to the ECASSIII criteria at 90-day (± 7 days)

**Time Frame:** at 90-day (± 7 days)

**Measure:** PH2 type intracranial hemorrhage according to the SITS criteria at 90-day (± 7 days)

**Time Frame:** at 90-day (± 7 days)

**Measure:** Any intracranial hemorrhage at 90-day (± 7 days)

**Time Frame:** at 90-day (± 7 days)

**Measure:** Moderate and severe bleeding events according to the GUSTO criteria at 90-day (± 7 days)

**Time Frame:** at 90-day (± 7 days)

**Measure:** Total mortality at 90-day (± 7 days)

**Time Frame:** at 90-day (± 7 days)

**Measure:** Adverse events/Severe adverse events reported by investigators at 90-day (± 7 days)

**Time Frame:** at 90-day (± 7 days)

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria

1. Age ≥ 18 years;
2. Can be treated with study drug within 4.5 hours of symptoms onset\*(\*Symptom onset is defined by the "last seen normal" principle);
3. Clinical diagnosis of minor ischemic stroke (baseline NIHSS≤5) with a measurable neurological deficit defined as impairment of language or motor function;
4. Pre-stroke mRS 0-1;
5. Informed consent signed.

Exclusion Criteria

1. Planned or likely to receive acute endovascular treatments (any angioplasty or vascular surgery);
2. NIHSS 1a \> 2;
3. Known allergic to rhTNK-tPA;
4. Known history of intracranial hemorrhage;
5. Clinical stroke or serious head/spinal trauma within 3 months;
6. Intracranial or spinal surgery within 3 months;
7. Known history of gastrointestinal or urinary tract hemorrhage in the previous 21 days.
8. Participants with a history of major surgery in the previous 14 days;
9. Arterial puncture at a non-compressible site in the previous 7 days.
10. Participants with intracranial tumors (excluding neuroectoderm origin, such as meningioma), huge intracranial aneurysm, or arterio-venous malformation.
11. Intracranial hemorrhage (including cerebral parenchymal hemorrhage, intraventricular hemorrhage, subarachnoid hemorrhage, subdural/epidural hematoma)
12. Participants with active visceral bleeding;
13. Participants with aortic arch dissection;
14. Participants with a known bleeding diathesis or with a platelet count \< 100×10\^9/L;
15. Participants with a systolic blood pressure ≥ 180 or a diastolic blood pressure ≥ 100 mmHg after repeated measurements and aggressive treatments;
16. Blood glucose \<50 or \> 400 mg/dl (\< 2.8 or \> 22.2 mmol / l);
17. Clear indication for anticoagulation (presumed cardiac source of embolus, e.g., atrial fibrillation, prosthetic cardiac valves known or suspected endocarditis);
18. Receive intravenous thrombolysis within 24 hours;
19. Receive direct oral anticoagulant therapy with international normalized ratio (INR) \> 1.7s or PT \> 15 s;
20. Receive low molecular weight heparin or heparinoid within 24 hours;
21. Receive thrombin inhibitors or factor Xa inhibitors within 48 hours;
22. Receive GP2b3a inhibitors within 72 hours;
23. Participants who have large areas (greater than one third of middle cerebral artery territory) of obvious low density on the baseline CT scan;
24. Participants with a seizure at onset thought to be presenting with postictal paralysis (Todd's paralysis) mimicking stroke.
25. Participants with severe infection, such as bacterial endocarditis, pericarditis, acute pancreatitis;
26. Pregnant, currently trying to become pregnant, or of child-bearing potential and not using birth control;
27. Participation in another clinical study with an experimental product in the previous 3 months;
28. Participants deemed unsuitable for participation in this trial by the investigator or those for whom participation in this trial may result in greater risks.

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** yongjunwang@ncrcnd.org.cn

**Name:** Yongjun Wang, MD, PhD

**Phone:** 86-13911172565

**Role:** CONTACT

**Contact 2:**

**Email:** jingj_bjttyy@163.com

**Name:** Jing Jing, MD, PhD

**Phone:** 86-15810312511

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Beijing

**Contacts:**

***Contact 1:***

- **Email:** yongjunwang111@aliyun.com

- **Name:** Yongjun Wang, Dr.

- **Role:** CONTACT

**Country:** China

**Facility:** Beijing Tiantan Hospital

**State:** Beijing

**Status:** RECRUITING

#### Overall Officials

**Official 1:**

**Affiliation:** Beijing Tiantan Hospital

**Name:** Yongjun Wang, MD, PhD

**Role:** STUDY_DIRECTOR

### IPD Sharing Statement Module

**IPD Sharing:** NO

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000020521

- Term: Stroke

- ID: D000002561

- Term: Cerebrovascular Disorders

- ID: D000001927

- Term: Brain Diseases

- ID: D000002493

- Term: Central Nervous System Diseases

- ID: D000009422

- Term: Nervous System Diseases

- ID: D000014652

- Term: Vascular Diseases

- ID: D000002318

- Term: Cardiovascular Diseases

- ID: D000010335

- Term: Pathologic Processes

### Condition Browse Module - Browse Branches

- Abbrev: BC10

- Name: Nervous System Diseases

- Abbrev: BC14

- Name: Heart and Blood Diseases

- Abbrev: All

- Name: All Conditions

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M22306

- Name: Stroke

- Relevance: LOW

- As Found: Unknown

- ID: M2400

- Name: Ischemic Stroke

- Relevance: HIGH

- As Found: Ischemic Stroke

- ID: M10543

- Name: Ischemia

- Relevance: HIGH

- As Found: Ischemic

- ID: M5810

- Name: Cerebrovascular Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M5204

- Name: Brain Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M5742

- Name: Central Nervous System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M17400

- Name: Vascular Diseases

- Relevance: LOW

- As Found: Unknown

- ID: T170

- Name: Acute Graft Versus Host Disease

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000083242

- Term: Ischemic Stroke

- ID: D000007511

- Term: Ischemia

### Intervention Browse Module - Browse Branches

- Abbrev: PhSol

- Name: Pharmaceutical Solutions

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: PlAggInh

- Name: Platelet Aggregation Inhibitors

- Abbrev: Antipy

- Name: Antipyretics

- Abbrev: Infl

- Name: Anti-Inflammatory Agents

- Abbrev: ARhu

- Name: Antirheumatic Agents

- Abbrev: FiAg

- Name: Fibrinolytic Agents

- Abbrev: Analg

- Name: Analgesics

### Intervention Browse Module - Browse Leaves

- ID: M21860

- Name: Pharmaceutical Solutions

- Relevance: LOW

- As Found: Unknown

- ID: M1669

- Name: Clopidogrel

- Relevance: LOW

- As Found: Unknown

- ID: M4548

- Name: Aspirin

- Relevance: LOW

- As Found: Unknown

- ID: M1812

- Name: Ticagrelor

- Relevance: LOW

- As Found: Unknown

- ID: M13849

- Name: Tissue Plasminogen Activator

- Relevance: LOW

- As Found: Unknown

- ID: M1911

- Name: Tenecteplase

- Relevance: LOW

- As Found: Unknown

### Misc Info Module

- Version Holder: 2024-05-31
