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

Official title

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

Overview

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).

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.

Interventions

• 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.
• Drug Standard medical treatment
  Patients in the control arm will receive standard medical treatment.

Primary outcome measures

• Excellent functional outcome [Time frame: at 90 (±14) days]

Secondary outcome measures (9)

• Ordinal distribution of mRS [Time frame: at 90 (±14) days]
• Favorable functional outcome [Time frame: at 90 (±14) days]
• Change in NIHSS Score at 24 (±12) hours [Time frame: at 24 (±12) hours]
• Change in NIHSS Score at 7 (±1) days or discharge [Time frame: at 7 (±1) days or discharge]
• Quality of life (EQ-5D-5L) [Time frame: at 90 (±14) days]
• Symptomatic intracranial hemorrhage [Time frame: within 36 hours]
• Any intracranial hemorrhage [Time frame: within 36 hours]
• Major extracranial bleeding [Time frame: within 36 hours]
• Mortality [Time frame: within 90 days]

Eligibility criteria

Inclusion criteria

• Age 18 years or older.
• Presumed acute ischemic stroke of the anterior circulation.
• 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'.
• Baseline National Institutes of Health Stroke Scale (NIHSS) 6-25 (inclusive).
• Limited early ischemic changes on non-contrast CT (NCCT).
• Written informed consent signed by patients or their legally authorized representatives.

Exclusion criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

China · 1 center

• Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University — Guangzhou

Identifiers

NCT: NCT07606807 · SYSKY-2026-479-02

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗