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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Ischemic Stroke
• Intervention / Treatment: Drug: Tenecteplase

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • None Selected
    • Shenyang, None Selected, China, 110840
      • Recruiting
      • Yu Cui
      • Contact: Yu Cui; Phone Number: 02428897499; Email: cuiyu.spu@hotmail.com

Participation Criteria

Eligibility Criteria

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

Description

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.

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: TNK group; Tenecteplase is administered intravenously at a dose of 16 mg, with a maximum dose of 0.25 mg/kg.	Drug: Tenecteplase; Tenecteplase is administered intravenously at a dose of 16 mg, with a maximum dose of 0.25 mg/kg.
No Intervention: Control group; No tenecteplase

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
proportion of excellent functional outcome (modified Rankin Scale (mRS) 0-1)	The minimum and maximum values of mRS are 0 and 6, respectively; higher score mean a worse outcome	90±7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
proportion of modified Rankin Scale (mRS) 0-2	The minimum and maximum values of mRS are 0 and 6, respectively; higher score mean a worse outcome	90±7 days
ordinal distribution of modified Rankin Scale (mRS)	The minimum and maximum values of mRS are 0 and 6, respectively; higher score mean a worse outcome	90±7 days
new stroke or other vascular event(s)		90±7 days
all-cause mortality		90±7 days
major systemic bleeding event		24 (-6/+12) hours
any bleeding event		24 (-6/+12) hours
symptomatic intracranial hemorrhage (sICH)		24 (-6/+12) hours
any intracranial hemorrhage		24 (-6/+12) hours
occurrence of early neurological improvement (ENI)	ENI is defined as more than 4-point decrease in National Institute of Health stroke scale score (NIHSS); the minimum and maximum values of NIHSS are 0 and 42, respectively; higher NIHSS mean a worse outcome	24 (-6/+12) hours
change in National Institute of Health stroke scale (NIHSS) score	the minimum and maximum values of National Institute of Health stroke scale (NIHSS) are 0 and 42, respectively; higher NIHSS score mean a worse outcome	24 (-6/+12) hours
change in National Institute of Health stroke scale (NIHSS) score	the minimum and maximum values of National Institute of Health stroke scale (NIHSS) are 0 and 42, respectively; higher NIHSS score mean a worse outcome	10±2 days

Collaborators and Investigators

• Sponsor: General Hospital of Shenyang Military Region

Study record dates

Study Major Dates

• Study Start (Actual): March 25, 2026
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): December 30, 2027

Study Registration Dates

• First Submitted: January 22, 2026
• First Submitted That Met QC Criteria: January 22, 2026
• First Posted (Actual): January 29, 2026

Study Record Updates

• Last Update Posted (Actual): April 1, 2026
• Last Update Submitted That Met QC Criteria: March 31, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• 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: Y (2025) 501

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No