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BRETIS-TNK

Intra-arterial tenecteplase during thrombectomy for acute stroke (BRETIS-TNK II): rationale and design

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Year of Publication: 2024

Authors: Zi-Ai Zhao, Jing Qiu, Wei Li, ..., Hui-Sheng Chen

Journal: Stroke & Vascular Neurology

Citation: Stroke Vasc Neurol 2024;9:e002377. doi:10.1136/svn-2023-002377

Link: https://doi.org/10.1136/svn-2023-002377

PDF: https://www.researchgate.net/profile/Hui...mxpY2F0aW9uIn19

Clinical Question

Does intra-arterial tenecteplase during endovascular treatment improve clinical outcomes in acute ischemic stroke patients with large vessel occlusion?

Bottom Line

Protocol paper for the first RCT of intra-arterial tenecteplase during EVT for LVO stroke. Two-phase IA-TNK strategy: 4mg distal to clot pre-retrieval, then continuous infusion during stent retriever deployment. Pilot showed first-pass reperfusion 53.8% vs 36.0% and 90-day good outcome 50% vs 34.6%. Planned 380 patients, ~30 Chinese centers. Adaptive enrichment design with interim at n=150.

        Major Points
        First RCT of IA-TNK during (not after) EVT for LVO stroke. Protocol paper — no results yet.
Unique two-phase IA strategy: 4mg TNK distal to clot, then 0.4 mg/min during retriever deployment.
Max cumulative IA-TNK: 9-12 mg depending on number of passes.
Pilot (BRETIS-TNK): first-pass reperfusion 53.8% vs 36.0%; good outcome 50% vs 34.6%.
Planned 380 patients (190/arm), ~30 Chinese centers. 80% power for 15% absolute improvement.
Adaptive enrichment: interim at n=150 may adjust dose, remove subgroups, or terminate.
0-24h window, anterior + posterior circulation. ASPECTS ≥6.
Dose reduced to 0.15 mg/min if concurrent IV thrombolysis.
Builds on CHOICE trial (IA alteplase post-EVT) with TNK instead.
ClinicalTrials.gov NCT05657444. Enrollment March 2023 to March 2025.

      

Design

Study Type: Randomized, open-label, blinded-endpoint, adaptive enrichment trial

Randomization: 1

Blinding: Outcomes assessed by blinded assessors

Enrollment Period: March 2023 to March 2025

Follow-up Duration: 90 days

Centers: 30

Countries: China

Sample Size: 380

Analysis: Intention-to-treat; logistic regression, ANOVA, Cox regression; stratified by age, NIHSS, ASPECTS, prior IVT use, stroke subtype

Inclusion Criteria

Age ≥18 years
Large vessel occlusion (ICA, M1, M2, basilar, intracranial vertebral artery)
Eligible for endovascular treatment within 24 hours
Pre-stroke mRS ≤2
ASPECTS ≥6
Informed consent obtained

Exclusion Criteria

Hemorrhagic stroke
Tandem occlusion
Coagulopathy, thrombocytopenia (<100,000/mm3)
Severe hepatic/renal dysfunction
Severe uncontrolled hypertension (SBP >200 or DBP >110 mm Hg)
Contraindication to study drugs
Pregnancy or breastfeeding
Suspected septic embolus or endocarditis
Life expectancy <6 months from other causes
Other investigator-determined reasons

Baseline Characteristics

Characteristic	Control	Active
Pre-stroke mRS	≤2	≤2
ASPECTS	≥6	≥6

Arms

Field	Intra-arterial TNK + EVT	Control
Intervention	Intra-arterial TNK (4 mg distal to clot, then 0.4 mg/min for 5 min during first stent retriever release; followed by 0.15–0.2 mg/min infusion depending on recanalization success and prior IVT)	Standard mechanical thrombectomy using local practices; no intra-arterial thrombolysis
Duration	Single EVT session; TNK up to 12 mg per procedure	Single EVT session

Outcomes

Outcome	Type	Control	Intervention	HR / OR / RR	P-value
Proportion of patients with mRS 0–2 at 90±7 days	Primary
mRS 0–1 at 90±7 days	Secondary
Successful reperfusion (mTICI 2b–3) after first or final pass	Secondary
Early neurological improvement (≥4 point NIHSS drop within 24h)	Secondary
Symptomatic ICH	Adverse
Parenchymal hemorrhage (PH1, PH2)	Adverse
Death (7-day or in-hospital)	Adverse
Severe adverse events (within 24h)	Adverse

Subgroup Analysis

Planned stratification by age, sex, SBP, baseline NIHSS and ASPECTS, stroke territory and etiology, time from onset to puncture, prior IVT, and anesthesia type

Criticisms

Trial not yet completed; results pending
Adaptive design may limit comparison to traditional RCTs
Complex intervention protocol could reduce generalizability

Funding

Science and Technology Project Plan of Liao Ning Province (2022JH2/101500020); Tenecteplase donated by CSPC Recomgen Pharmaceutical (Guangzhou)

Based on: BRETIS-TNK (Stroke & Vascular Neurology, 2024)