rhTNK-tPA for Acute Ischemic Stroke Under Simplified Imaging in the Extended Time Window (SIMPLIFIED)

rhTNK-tPA for Acute Ischemic Stroke Under Simplified Imaging in the Extended Time Window: A Multicenter, Prospective, Randomized Controlled, Open-label, Blinded-Endpoint Trial

The PEARL-SIMPLIFIED trial is a multicenter, prospective, randomized controlled, open-label, blinded-endpoint study. It aims to evaluate the efficacy and safety of intravenous tenecteplase (TNK) in patients with acute ischemic stroke (AIS) presenting in the extended 4.5-24 hour window, using a simplified imaging selection strategy based solely on non-contrast CT (NCCT).

Study Overview

• Status: Not yet recruiting
• Conditions: Acute Ischemic Stroke
• Intervention / Treatment: Drug: Tenecteplase (rhTNK-tPA) (0.25 mg/kg, to maximum of 25mg); Drug: Standard medical treatment

Detailed Description

The PEARL-SIMPLIFIED trial is a multicenter, prospective, randomized controlled, open-label, blinded-endpoint study with a target enrollment of at least 750 patients. The trial focuses on individuals with acute ischemic stroke (AIS) presenting within a 4.5 to 24-hour window who are not planned for endovascular thrombectomy (EVT). Patients meeting simplified imaging criteria based on non-contrast CT (NCCT) are randomized 1:1 to receive a single intravenous bolus of 0.25 mg/kg tenecteplase (TNK) or standard medical treatment. The primary outcome is the 90-day excellent functional outcome, defined as a modified Rankin Scale (mRS) score of 0-1. Safety outcomes include symptomatic intracranial hemorrhage (sICH) and 90-day mortality.

• Study Type: Interventional
• Enrollment (Estimated): 750
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Jinyuan Wang; Phone Number: 86-18558992193; Email: wangjy257@mail2.sysu.edu.cn
• Study Contact Backup: Name: Xinguang Yang, MD, PhD; Email: yangxinguang0926@163.com

Study Locations

• China
  • Guangzhou, China, 510120
    • Sun Yat-sen Memorial Hospital, Sun Yat-sen University
    • Contact: Jinyuan Wang; Phone Number: 86-20-81332619; Email: wangjy257@mail2.sysu.edu.cn
    • Contact: Xinguang Yang, MD, PhD; Email: yangxinguang0926@163.com
    • Principal Investigator: Yamei Tang, MD, PhD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age 18 years or older.
2. Presumed acute ischemic stroke of the anterior circulation.
3. Acute ischemic stroke symptom onset between 4.5 to 24 hours prior to enrollment; including wake-up stroke and unwitnessed stroke, onset time refers to 'last-known well time'.
4. Baseline National Institutes of Health Stroke Scale (NIHSS) 6-25 (inclusive).
5. Limited early ischemic changes on non-contrast CT (NCCT).
6. Written informed consent signed by patients or their legally authorized representatives.

Exclusion Criteria:

1. Clearly demarcated hypodensity on non-contrast CT related to the current stroke, with limited anticipated clinical benefit as judged by the investigator.
2. Intracranial or subarachnoid hemorrhage identified on baseline NCCT.
3. Endovascular thrombectomy (EVT) planned at the time of randomization.
4. Pre-stroke mRS≥2.
5. Allergy to the test drug and its ingredients.
6. Severe head trauma or ischemic stroke in the last 3 months.
7. Intracranial or intraspinal surgery within 3 months before enrollment.
8. Intracranial tumor or large-size aneurysm found before enrollment.
9. Gastrointestinal or urinary system hemorrhage within the past 3 weeks.
10. Active visceral bleeding.
11. Aortic arch dissection confirmed by examination or medical history.
12. Infective endocarditis confirmed by examination or medical history.
13. Platelet count less than 100 × 109 /L.
14. Patients received heparin or low-molecular-weighted heparin treatment within 24h before enrollment.
15. Pregnant or lactating women.
16. Blood glucose <50 mg/dl (2.78mmol/L) or >400 mg/dl (22.2mmol/L) during screening.
17. Uncontrolled hypertension with persistent systolic blood pressure >185 mmHg or diastolic blood pressure >110 mmHg, refractory to medical management.
18. Life expectancy less than 6 months due to malignancy, severe cardiopulmonary disease, or other terminal illness.
19. Participating in other trials.
20. Other conditions deemed unsuitable for the study by the investigator, such as inability to comprehend or comply with study procedures or follow-up due to mental illness, cognitive or emotional disorder.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention Arm; Intravenous tenecteplase	Drug: Tenecteplase (rhTNK-tPA) (0.25 mg/kg, to maximum of 25mg); Patients randomized to the intervention arm will receive tenecteplase via a single intravenous bolus (0.25 mg/kg; maximum dose 25 mg), administered immediately following randomization.
Active Comparator: Control Arm; Standard medical treatment	Drug: Standard medical treatment; Patients in the control arm will receive standard medical treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Excellent functional outcome	The proportion of mRS score 0-1 at 90 (±14) days.	at 90 (±14) days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ordinal distribution of mRS	The proportion of mRS distribution at 90 (±14) days	at 90 (±14) days
Favorable functional outcome	The proportion of mRS score 0-2 at 90 (±14) days	at 90 (±14) days
Change in NIHSS Score at 24 (±12) hours	NIHSS score change from baseline at 24 (±12) hours	at 24 (±12) hours
Change in NIHSS Score at 7 (±1) days or discharge	NIHSS score change from baseline at 7 (±1) days or discharge	at 7 (±1) days or discharge
Quality of life (EQ-5D-5L)	Quality of life measured by EQ-5D-5L at 90 (±14) days	at 90 (±14) days
Symptomatic intracranial hemorrhage	Symptomatic intracranial hemorrhage (sICH) within 36 hours from randomization (SITS-MOST criteria)	within 36 hours
Any intracranial hemorrhage	Any intracranial hemorrhage within 36 hours	within 36 hours
Major extracranial bleeding	Major extracranial bleeding within 36 hours (GUSTO criteria: moderate and severe bleeding)	within 36 hours
Mortality	All-cause mortality within 90 days	within 90 days

Collaborators and Investigators

• Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
• Investigators: Principal Investigator: Yamei Tang, MD, PhD, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: April 22, 2026
• First Submitted That Met QC Criteria: May 19, 2026
• First Posted (Actual): May 26, 2026

Study Record Updates

• Last Update Posted (Actual): May 26, 2026
• Last Update Submitted That Met QC Criteria: May 19, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Tenecteplase; Intravenous Thrombolysis; Extended Time Window; Non-contrast CT; Simplified Imaging
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Stroke; Ischemic Stroke; Amino Acids, Peptides, and Proteins; Proteins; Hydrolases; Enzymes; Enzymes and Coenzymes; Blood Proteins; Endopeptidases; Peptide Hydrolases; Serine Endopeptidases; Serine Proteases; Plasminogen Activators; Blood Coagulation Factors; Tissue Plasminogen Activator; Tenecteplase
• Other Study ID Numbers: PEARL-SIMPLIFIED

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The IPD will be available from the Principal Investigator upon reasonable request 6 months after the trial completion.
• IPD Sharing Time Frame: 6 months after the trial completion.
• IPD Sharing Access Criteria: The IPD will be available from the Principal Investigator upon reasonable request 6 months after the trial completion.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No