Repeated Intravenous Thrombolysis for Ischemic Stroke Within 3.0 Hours of Onset With Tenecteplase (RITIS-TNK)

Official title

Repeated Intravenous Thrombolysis for Ischemic Stroke Within 3.0 Hours of Onset With Tenecteplase (RITIS-TNK): a Prospective, Randomized, Open Label, Blinded Assessment of Outcome, and Multi-center Study

Overview

Despite being the standard pharmacological reperfusion therapy for acute ischemic stroke, intravenous thrombolysis is limited by suboptimal recanalization rates. Tenecteplase (TNK), a newer thrombolytic agent, offers practical advantages over alteplase, including single bolus administration. However, a significant proportion of patients fail to achieve early clinical improvement after standard thrombolysis, likely due to persistent vessel occlusion. This study proposes to investigate a rescue strategy for patients who do not show significant neurological improvement within one hour after receiving standard intravenous tenecteplase within 3 hours of stroke onset. The primary objective is to evaluate the safety and feasibility of administering a second dose of tenecteplase in this scenario. The study will also explore the potential efficacy of this approach in improving recanalization and functional outcomes.

Interventions

• Drug Tenecteplase
  Tenecteplase is administered intravenously at a dose of 16 mg, with a maximum dose of 0.25 mg/kg.

Primary outcome measures

• proportion of excellent functional outcome (modified Rankin Scale (mRS) 0-1) [Time frame: 90±7 days]

Secondary outcome measures (11)

• proportion of modified Rankin Scale (mRS) 0-2 [Time frame: 90±7 days]
• ordinal distribution of modified Rankin Scale (mRS) [Time frame: 90±7 days]
• occurrence of early neurological improvement (ENI) [Time frame: 24 (-6/+12) hours]
• change in National Institute of Health stroke scale (NIHSS) score [Time frame: 24 (-6/+12) hours]
• change in National Institute of Health stroke scale (NIHSS) score [Time frame: 10±2 days]
• new stroke or other vascular event(s) [Time frame: 90±7 days]
• symptomatic intracranial hemorrhage (sICH) [Time frame: 24 (-6/+12) hours]
• any intracranial hemorrhage [Time frame: 24 (-6/+12) hours]
• major systemic bleeding event [Time frame: 24 (-6/+12) hours]
• any bleeding event [Time frame: 24 (-6/+12) hours]
• all-cause mortality [Time frame: 90±7 days]

Eligibility criteria

Inclusion criteria

• Age ≥ 18 year;
• Acute ischemic stroke within 3 hours of onset, having received standard intravenous thrombolysis;
• Measurable neurological deficit before the first intravenous thrombolysis, with NIHSS ≥ 4;
• No significant clinical improvement (reduction in NIHSS ≤ 2) or neurological deterioration after initial improvement at 1 hour after the first thrombolysis, with intracranial hemorrhage ruled out by neuroimaging;
• The second intravenous thrombolysis can be administered within 4.5 hours of onset;
• First stroke onset or past stroke without obvious neurological deficit (mRS≤1);
• Signed informed consent.

Exclusion criteria

• Planed for endovascular treatment;
• Significant cerebral white matter hyperintensities (Fazekas score 3)；
• Any coagulation abnormality before the first thrombolysis, including INR > 1.5；
• Pregnancy；
• Allergy to the investigational drug(s)；
• Receipt of dual antiplatelet therapy within 24 hours prior to thrombolysis;
• Comorbidity with other serious diseases;
• Participating in other clinical trials within 3 months;
• Patients not suitable for the study considered by researcher.

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

• Yu Cui — Shenyang

Identifiers

NCT: NCT07375953 · Y (2025) 501

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗