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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://doi.org/10.1161/strokeaha.124.048375

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

Clinical Question

Is IV tenecteplase 0.25 mg/kg effective and safe for patients with ischemic stroke due to anterior-circulation large/medium vessel occlusion within 4.5–24 hours of last known well when selected by CT perfusion mismatch?

Study Overview

Objective

To determine whether IV tenecteplase is effective and safe in achieving reperfusion in large/medium vessel occlusion strokes up to 24 hours from last known well using perfusion imaging selection.

Study Summary

Tenecteplase significantly increased reperfusion (33.3% vs 10.8%) without increasing symptomatic ICH.
No significant difference in NIHSS outcomes at 24–48 hours or in 90-day mRS 0–2.
Safety outcomes were similar.

Intervention

Tenecteplase 0.25 mg/kg IV bolus up to 25 mg within 4.5–24 hours from last known well.

Bottom Line

Tenecteplase 0.25 mg/kg IV in the 4.5–24 hour window significantly increased major reperfusion and recanalization but did not change 90-day functional outcomes compared with best medical treatment; symptomatic ICH rates were similar.

        Major Points
        CHABLIS-T II was a multicenter, phase IIb, block-randomized, open-label, blinded-endpoint trial comparing IV tenecteplase 0.25 mg/kg with best medical treatment (BMT) in 224 anterior-circulation LVO/MeVO ischemic stroke patients presenting 4.5–24 hours from last known well, selected by CTP mismatch (delay time >3s ratio >1.2, absolute mismatch >10 mL, core <70 mL).
Primary composite (major reperfusion without sICH at 24–48 h) occurred in 33.3% of tenecteplase vs 10.8% of BMT patients (adjusted RR 3.0, 95% CI 1.6–5.7; P=0.001).
Recanalization at initial catheter angiography or 4- to 6-h repeat CTA was higher with tenecteplase (35.8% vs 14.3%; adjusted RR 2.5, 95% CI 1.4–4.4; P=0.002).
No significant difference in 90-day functional outcomes (mRS 0–1: 39.6% tenecteplase vs 36.3% BMT, P=0.8; mRS 0–2: 50.5% vs 58.4%, P=0.4; ordinal cOR 0.8, P=0.3).
Symptomatic ICH occurred in 5.4% tenecteplase vs 4.4% BMT (aRR 1.3, P=0.7); parenchymal hematoma type 2 numerically higher (9.0% vs 3.5%, P=0.1). In the preplanned-EVT subgroup, tenecteplase strongly increased reperfusion but showed a trend toward larger infarct growth and worse mRS shift.

      

Design

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

Randomization: 1

Blinding: Open-label with blinded outcome assessment (central core imaging lab; independent neuroradiologists)

Enrollment Period: October 2021 to June 2023

Follow-up Duration: 90 days

Centers: 23

Countries: China

Sample Size: 224

Analysis: Intention-to-treat; modified Poisson regression with log-link and robust error variance; adjusted for time from last known well to randomization (4.5–9 vs 9–24 h), site of vessel occlusion (internal carotid artery vs other), and whether EVT was preplanned (yes vs no); ordinal analysis of 90-day mRS via ordinal regression (common odds ratio); infarct-growth via median regression

Inclusion Criteria

Age 18–80 years
Premorbid modified Rankin Scale (mRS) 0–2
Acute ischemic stroke with a clinically significant NIHSS-defined neurological deficit
Time from last known well 4.5–24 hours
Large or medium vessel occlusion in the anterior circulation on CTA (extracranial/intracranial ICA, M1, M2, A1, A2)
Favorable perfusion mismatch on CTP: hypoperfusion (delay time >3s) to ischemic core (rCBF <30%) ratio >1.2, absolute mismatch volume >10 mL, and ischemic core volume <70 mL

Exclusion Criteria

Posterior circulation stroke
Absence of favorable perfusion mismatch
Presence of intracranial hemorrhage on baseline imaging
High bleeding risk or contraindications to thrombolysis
Prestroke mRS >2
Other comorbidities affecting safety or interpretation (per protocol)

Baseline Characteristics

Characteristic	Control	Active
Mean Age	63.6 ± 11.0	64.2 ± 10.4
Male %	70.8%	72.1%
NIHSS	9 (6-16), median (IQR)	9 (5-14), median (IQR)
Hypertension	69.9%	64.0%
Diabetes	23.0%	28.8%
Preplanned EVT	56.6%	53.2%

Arms

Field	Tenecteplase	Control
Intervention	Single IV bolus of tenecteplase 0.25 mg/kg (max 25 mg) over 5–10 seconds, followed by a 2 mL saline flush	Best medical treatment excluding tenecteplase; IV alteplase permitted within the EXTEND (Extending the Time for Thrombolysis in Emergency Neurological Deficits) time-window; emergent EVT optional at neurointerventionalist's discretion
Duration	Single administration	As indicated

Outcomes

Outcome	Type	Control	Intervention	HR / OR / RR	P-value
Major reperfusion (restoration of blood flow >50% of the involved ischemic territory) without symptomatic intracranial hemorrhage within 24–48 hours after randomization; assessed at initial catheter angiography (for preplanned EVT) or on 4- to 6-hour repeat CTP (hypoperfusion volume decreased to <50% of baseline)	Primary	10.8% (12/111)	33.3% (37/111)	Adjusted RR 3.0 (95% CI 1.6–5.7)	0.001
Recanalization at initial catheter angiography or 4- to 6-hour repeat CTA	Secondary	14.3% (16/112)	35.8% (39/109)	Adjusted RR 2.5 (95% CI 1.4–4.4)	0.002
mRS 0–1 at 90 days	Secondary	36.3% (41/113)	39.6% (44/111)	Adjusted RR 1.1 (95% CI 0.7–1.6)	0.8
mRS 0–2 at 90 days	Secondary	58.4% (66/113)	50.5% (56/111)	Adjusted RR 0.8 (95% CI 0.6–1.2)	0.4
mRS distribution at 90 days (ordinal shift)	Secondary			Adjusted common OR 0.8 (95% CI 0.5–1.3)	0.3
Major neurological improvement at 24–48 h (≥8-point NIHSS reduction or NIHSS 0–1)	Secondary	23.1% (26/112)	21.8% (24/110)	Adjusted RR 0.9 (95% CI 0.5–1.6)	0.8
Change in NIHSS from baseline to 24–48 h, median (IQR)	Secondary	-1 (-5 to 0)	-1 (-4 to 0)	Adjusted difference 0.2 (-1.0 to 1.4)	0.7
Infarct growth at 3–5 days, mL, median (IQR)	Secondary	16.5 (2.6–42.3)	18.9 (4.2–59.6)	Adjusted difference 5.0 (-2.8 to 12.9)	0.2
Symptomatic ICH	Adverse	4.4% (5/113)	5.4% (6/111)	Adjusted RR 1.3 (95% CI 0.4–4.2)	0.7
Any ICH at 24–48 h	Adverse	18.6% (21/113)	24.3% (27/111)	Adjusted RR 1.4 (95% CI 0.8–2.4)	0.3
Parenchymal Hematoma Type 2 at 24–48 h	Adverse	3.5% (4/113)	9.0% (10/111)	Adjusted RR 2.7 (95% CI 0.8–8.5)	0.1
mRS 5–6 at 90 days (poor functional outcome)	Adverse	17.7% (20/113)	19.8% (22/111)	Adjusted RR 1.1 (95% CI 0.6–2.1)	0.7
Systemic Bleeding before discharge	Adverse	6.2% (7/113)	4.5% (5/111)	Adjusted RR 0.8 (95% CI 0.2–2.4)	0.6

Subgroup Analysis

Preplanned EVT interaction: tenecteplase markedly improved the primary composite in EVT-treated patients (27.6% [16/58] vs 1.6% [1/64]; adjusted RR 18.5, 95% CI 2.5–139.2; P=0.005; P interaction=0.01) and recanalization (37.9% vs 6.3%; adjusted RR 6.3, 95% CI 2.2–18.2; P=0.001; P interaction=0.01). In patients without preplanned EVT, tenecteplase still increased reperfusion (39.6% vs 23.4%; aRR 1.6, 95% CI 0.8–3.4). However, within the preplanned-EVT subgroup, tenecteplase showed trends toward larger infarct growth and a worse 90-day mRS distribution (cOR 0.5, 95% CI 0.3–0.98; P=0.04; P interaction=0.06).

Criticisms

Trial was underpowered for 90-day functional outcomes; primary endpoint was a composite of imaging reperfusion and safety, not clinical function.
Highly selected population — only 3.6% (224/6205) of screened patients enrolled, limiting generalizability.
Nonstandard mismatch criteria (delay time >3s with mismatch volume >10 mL and ratio >1.2) rather than the more commonly used Tmax >6s with 15 mL / ratio 1.8.
Trend toward larger infarct growth and worse mRS shift in the tenecteplase + preplanned-EVT subgroup not fully explained.
Open-label design (with blinded endpoint) leaves potential for bias in management decisions.
Predominantly (~76%) large-artery atherosclerotic stroke and exclusively Chinese population limits generalizability to other stroke etiologies and populations.

Funding

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

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