Repeated intravenous thrombolysis for ischaemic stroke with medium to large vessel occlusion presenting within 4.5 hours of onset with tenecteplase in China (RITIS-TNK2): protocol for a prospective, randomised, open-label, blinded assessment of outcome and multicentre study.
RITIS-TNK2 is a prospective, randomised, open-label, blinded endpoint, multicentre, superiority trial designed to evaluate the efficacy and safety of a second intravenous dose of tenecteplase (0.25 mg/kg, capped at 16 mg) in acute ischaemic stroke patients with persistent medium or large vessel occlusion 1 hour after standard intravenous thrombolysis.
Key Findings
Background
Recanalisation rates following standard intravenous thrombolysis for acute ischaemic stroke due to medium or large vessel occlusion remain unsatisfactory, motivating investigation of a rescue second dose strategy.
The study targets patients with acute anterior and posterior circulation MeVO/LVO who have not recanalised 1 hour after standard IVT.
The expected recanalisation rate at 24 hours in the control group (standard medical care alone) is estimated at 45%.
Poor recanalisation rates are described as leading to poor clinical outcomes.
Background
Tenecteplase is described as having potential advantages over alteplase, including higher recanalisation rates in large vessel occlusion.
Tenecteplase is characterised as a fibrin-specific thrombolytic agent.
Preliminary evidence is cited suggesting that a second dose of thrombolytic in patients with persistent vessel occlusion after initial IVT 'may be feasible and beneficial.'
The trial uses TNK as the rescue agent rather than alteplase.
Methods
The trial protocol randomly assigns eligible patients 1:1 to receive a second dose of tenecteplase plus standard medical care or standard medical care alone.
The second dose of TNK is 0.25 mg/kg intravenously, capped at a maximum total dose of 16 mg.
The second dose is administered to patients who have not recanalised 1 hour after standard IVT.
The design is prospective, randomised, open-label, blinded endpoint (PROBE), and multicentre.
The trial is a superiority design with a two-sided 0.05 level of significance.
Methods
The primary efficacy outcome is the recanalisation rate of the occluded artery at 24 hours after randomisation, and the primary safety outcome is symptomatic intracranial haemorrhage within 24 hours.
Secondary outcomes include functional status at 90 days assessed by the modified Rankin Scale score.
The trial covers both anterior and posterior circulation MeVO/LVO.
Patients are eligible if presenting within 4.5 hours of stroke onset.
Methods
The study hypothesises that rescue tenecteplase will raise the 24-hour recanalisation rate from 45% to 65%, representing an absolute 20 percentage-point improvement and a relative 44.4% increase.
A maximum of 198 patients are required to test the superiority hypothesis.
The sample size provides 80% statistical power at a two-sided 0.05 significance level.
The trial is registered as NCT07375966 and approved by the General Hospital of Northern Theater Command IRB: Y (2025) 502.
The study is conducted in China and described as multicentre.
What This Means
This paper describes the design of a clinical trial called RITIS-TNK2, which is testing whether giving a second dose of a clot-dissolving drug (tenecteplase) to stroke patients can improve outcomes when the first dose fails to reopen a blocked blood vessel. Currently, when someone has an ischaemic stroke caused by a blocked medium or large artery, doctors give a clot-busting drug intravenously, but this only successfully reopens the artery in roughly half of patients. The trial will enroll up to 198 patients in China who arrive within 4.5 hours of their stroke and still have a blocked artery one hour after their initial treatment. Half will receive a second dose of tenecteplase (0.25 mg/kg, maximum 16 mg) on top of standard care, and half will receive standard care alone.
This research suggests that if the second dose works as hypothesised, it could raise the rate of artery reopening at 24 hours from about 45% to 65% — a meaningful improvement that could translate into better recovery for stroke patients. The trial is also carefully monitoring for the key safety risk of a second thrombolytic dose, namely bleeding inside the brain (symptomatic intracranial haemorrhage). Longer-term functional outcomes will be assessed at 90 days using a standard disability scale.
The practical significance of this study is that it addresses a common and frustrating gap in stroke care: patients who do not respond to initial clot-busting therapy currently have limited options if they cannot immediately access or are not candidates for mechanical clot removal. If a simple second intravenous injection proves safe and effective, it could offer an accessible rescue strategy, particularly in settings where advanced interventional stroke care is not readily available. The results will be published regardless of whether they are positive or negative.
Yao Z, Chen M, Wang L, Wang Y, Zhou Z, Chen H. (2026). Repeated intravenous thrombolysis for ischaemic stroke with medium to large vessel occlusion presenting within 4.5 hours of onset with tenecteplase in China (RITIS-TNK2): protocol for a prospective, randomised, open-label, blinded assessment of outcome and multicentre study.. BMJ open. https://doi.org/10.1136/bmjopen-2026-120918