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CHABLIS-T II

Tenecteplase Thrombolysis for Stroke up to 24 Hours After Onset With Perfusion Imaging Selection: The CHABLIS-T II Randomized Clinical Trial

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Year of Publication: 2025

Authors: Xin Cheng, Lan Hong, Longting Lin, ..., et al. on behalf of the CHABLIS-T II Collaborators

Journal: Stroke

Citation: Stroke. 2025;56:344–354. DOI: 10.1161/STROKEAHA.124.048375

Link: https://www.ahajournals.org/doi/10.1161/STROKEAHA.124.048375

PDF: https://www.ahajournals.org/doi/epub/10....EAHA.124.048375

Clinical Question

Is tenecteplase effective and safe for patients with ischemic stroke due to large/medium vessel occlusion within 4.5–24 hours of last known well using perfusion imaging selection?

Bottom Line

Tenecteplase significantly improved major reperfusion and recanalization but did not improve 90-day functional outcomes compared with best medical treatment. Symptomatic ICH rates were similar.

        Major Points
        CHABLIS-T II was a multicenter, phase IIb, randomized trial comparing IV tenecteplase with best medical treatment (BMT) in 224 ischemic stroke patients within 4.5–24 hours using perfusion imaging selection.
Tenecteplase significantly improved the rate of major reperfusion at 24–48h (33.3% vs 10.8%, RR 3.08, 95% CI 1.63–5.83).
Recanalization rate was also significantly higher in the tenecteplase group (35.8% vs 14.3%, RR 2.50, 95% CI 1.40–4.47).
There was no difference in 90-day functional outcomes (mRS 0–1: 30.6% vs 33.6%, P=0.67; mRS 0–2: 45% vs 46%, P=0.82).
Symptomatic ICH occurred in 5.4% of tenecteplase and 4.4% of BMT patients (P=0.70).

      

Design

Study Type: Multicenter, phase IIb, prospective, open-label, blinded-endpoint randomized clinical trial

Randomization: 1

Blinding: Open-label with blinded outcome assessment

Enrollment Period: October 2021 to June 2023

Follow-up Duration: 90 days

Centers: 23

Countries: China

Sample Size: 224

Analysis: Modified Poisson regression with robust standard errors; adjusted for time from last known well, vessel occlusion site, and EVT strategy

Inclusion Criteria

Age 18–80 years
Acute ischemic stroke with NIHSS-defined deficit
Time from last known well 4.5–24 hours
Anterior circulation large or medium vessel occlusion
Favorable perfusion mismatch (core <70 mL, mismatch ratio >1.2, mismatch volume >10 mL)

Exclusion Criteria

Posterior circulation stroke
Unfavorable perfusion profile
Presence of intracranial hemorrhage
High bleeding risk or thrombolysis contraindications
Prestroke mRS >2
Other comorbidities affecting safety or interpretation

Baseline Characteristics

Characteristic	Control	Active
Mean Age	64.3 ± 12.7	63.4 ± 12.6
Male %	70.8%	66.7%
NIHSS	13.5 ± 5.3	13.6 ± 5.4
Hypertension	62.8%	64.9%
Diabetes	29.2%	28.8%
Received EVT	67.3%	64.0%

Arms

Field	Tenecteplase	Control
Intervention	Single IV bolus of tenecteplase 0.25 mg/kg (max 25 mg)	Supportive medical care, including IV alteplase or EVT per physician discretion
Duration	Single administration	As indicated

Outcomes

Outcome	Type	Control	Intervention	HR / OR / RR	P-value
Major reperfusion (>50% perfused territory) without symptomatic ICH on follow-up perfusion imaging (24–48h)	Primary	10.8%	33.3%	Adjusted RR 3.0 (95% CI 1.5-5.8)	0.001
Recanalization	Secondary	14.3%	35.8%	RR 2.50 (95% CI 1.40–4.47)	0.002
mRS 0–1 at 90 days	Secondary	33.6%	30.6%		0.67
mRS 0–2 at 90 days	Secondary	46.0%	45.0%		0.82
NIHSS change from baseline to 24h	Secondary	-5.5 ± 5.0	-5.6 ± 5.3		0.94
Infarct growth	Secondary	37.2 ± 54.6 mL	35.7 ± 52.3 mL		0.86
Symptomatic ICH	Adverse	4.4%	5.4%		0.70
Any ICH	Adverse	18.6%	24.3%		0.30
Systemic Bleeding	Adverse	6.2%	4.5%		0.56

Subgroup Analysis

Tenecteplase improved reperfusion in EVT-treated patients (RR 2.91, 95% CI 1.49–5.69), but showed no functional benefit. Patients without EVT also had higher reperfusion with tenecteplase.

Criticisms

Trial was underpowered to detect differences in functional outcomes at 90 days.
Highly selected population (only 3.6% of screened patients enrolled), limiting generalizability.
Perfusion mismatch criteria were not based on standardized thresholds (used delay time >3s).
Trend toward worse infarct growth in EVT subgroup not fully explained.
Open-label design could introduce bias despite blinded endpoint assessment.

Funding

Clinical Research Plan of Shanghai Hospital Development Center (SHDC2020CR1041B); tenecteplase supplied by CSPC Recomgen

Based on: CHABLIS-T II (Stroke, 2025)