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

June 11, 2026 updated by: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

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

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
750

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • China
      • Guangzhou, China, 510120
        • Recruiting
        • Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University
        • Contact:
        • Contact:
        • Principal Investigator:
          • Yamei Tang, MD, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Excellent functional outcome
Time Frame: at 90 (±14) days
The proportion of mRS score 0-1 at 90 (±14) days.
at 90 (±14) days

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Ordinal distribution of mRS
Time Frame: at 90 (±14) days
The proportion of mRS distribution at 90 (±14) days
at 90 (±14) days
Favorable functional outcome
Time Frame: at 90 (±14) days
The proportion of mRS score 0-2 at 90 (±14) days
at 90 (±14) days
Change in NIHSS Score at 24 (±12) hours
Time Frame: 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
Time Frame: 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)
Time Frame: at 90 (±14) days
Quality of life measured by EQ-5D-5L at 90 (±14) days
at 90 (±14) days
Symptomatic intracranial hemorrhage
Time Frame: within 36 hours
Symptomatic intracranial hemorrhage (sICH) within 36 hours from randomization (SITS-MOST criteria)
within 36 hours
Any intracranial hemorrhage
Time Frame: within 36 hours
Any intracranial hemorrhage within 36 hours
within 36 hours
Major extracranial bleeding
Time Frame: within 36 hours
Major extracranial bleeding within 36 hours (GUSTO criteria: moderate and severe bleeding)
within 36 hours
Mortality
Time Frame: within 90 days
All-cause mortality within 90 days
within 90 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Yamei Tang, MD, PhD, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 1, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2028

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2028

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 22, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 19, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 26, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 15, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 11, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • SYSKY-2026-479-02

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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