Repeated Intravenous Thrombolysis for Ischemic Stroke With Medium to Large Vessel Occlusion Presenting Within 4.5 Hours of Onset With Tenecteplase (RITIS-TNK2) (RITIS-TNK2)

Repeated Intravenous Thrombolysis for Ischemic Stroke With Medium to Large Vessel Occlusion Presenting Within 4.5 Hours of Onset With Tenecteplase (RITIS-TNK2): a Prospective, Randomized, Open Label, Blinded Assessment of Outcome, and Multi-center Study

While intravenous thrombolysis (IVT) within 4.5 hours is the standard medical reperfusion therapy, its efficacy is limited, particularly for large or medium vessel occlusions (LVO/MeVO), with low recanalization rates for IVT with rt-PA. The newer thrombolytic agent, tenecteplase (TNK), offers practical advantages-including single bolus administration, a longer half-life, and potentially higher fibrin specificity-and has been shown to be non-inferior to rt-PA.

Despite advances, a significant proportion of patients with LVO/MeVO do not achieve early clinical improvement after standard IVT, likely due to persistent occlusion from a high thrombus burden. Endovascular therapy, while highly effective for LVO, has limited accessibility. Therefore, there is an urgent need for more effective and widely accessible pharmacological strategies.

This study proposes a rescue strategy based on the hypothesis that a second dose of IVT may improve outcomes in patients with imaging-confirmed LVO or MeVO who show no significant neurological improvement one hour after standard TNK thrombolysis (administered within 4.5 hours of stroke onset). The primary aim of this study is to formally evaluate the efficacy and safety of a repeated dose of intravenous tenecteplase in this specific patient population.

Study Overview

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

• Study Type: Interventional
• Enrollment (Estimated): 198
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Liaoning
    • Shenyang, Liaoning, China, 110840
      • Recruiting
      • Lu Wang
      • Contact: Yu Cui; Phone Number: 862428897491; 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 presumably caused by large or medium vessel occlusion within 4.5 hours of onset, having received standard-dose intravenous thrombolysis, and with no planned thrombectomy;
• Measurable neurological deficit before the first intravenous thrombolysis, with NIHSS ≥ 4;
• Baseline pc-ASPECTS/ASPECTS ≥ 6, and for posterior circulation infarction, a Pontine-Midbrain Index ≤ 2 (assessed by CT or DWI);
• No significant clinical improvement (reduction in NIHSS ≤ 2) or neurological deterioration after initial improvement at 1 hour after the first thrombolysis;
• Follow-up imaging (CTA or MRA) at 1 hour after the first thrombolysis rules out intracranial hemorrhage and confirms the presence of large or medium vessel occlusion (internal carotid artery, M1-M3 segments of the middle cerebral artery, A1-A3 segments of the anterior cerebral artery, P1-P3 segments of the posterior cerebral artery, basilar artery or V4 segment of the vertebral artery, PICA, AICA, or SCA);
• The second intravenous thrombolysis can be administered within 6 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 white matter hyperintensities (Fazekas score 3);
• Any coagulation abnormality before the first thrombolysis, including INR > 1.5;
• Receipt of dual antiplatelet therapy within 24 hours prior to thrombolysis.；
• Pregnancy；
• Allergy to the investigational drug(s)；
• 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	Time Frame
rate of vessel recanalization	24 (-6/+12) hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
all-cause mortality		10±2 days
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
change in National Institute of Health stroke scale (NIHSS) score	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 NIHSS are 0 and 42, respectively; higher NIHSS mean a worse outcome	10±2 days
proportion of favorable functional outcome (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
occurence of symptomatic intracranial hemorrhage (sICH)		24 (-6/+12) hours
occurence of any intracranial hemorrhage		24 (-6/+12) hours
occurence of major systemic bleeding event		24 (-6/+12) hours
occurence of any bleeding event		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; the minimum and maximum values of NIHSS are 0 and 42, respectively; higher NIHSS mean a worse outcome	24 (-6/+12) hours

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) 502

Drug and device information, study documents

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