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ROSE-TNK

Intravenous Tenecteplase for Acute Ischemic Stroke Within 4.5–24 Hours of Onset (ROSE-TNK): A Phase 2, Randomized, Multicenter Study

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Year of Publication: 2023

Authors: Lu Wang, Ying-Jie Dai, Yu Cui, ..., Hui-Sheng Chen

Journal: Journal of Stroke

Citation: J Stroke. 2023;25(3):371-377. doi:10.5853/jos.2023.00668

Link: https://doi.org/10.5853/jos.2023.00668

PDF: https://j-stroke.org/upload/pdf/jos-2023-00668.pdf

Clinical Question

Is intravenous tenecteplase safe and effective for treating acute ischemic stroke 4.5–24 hours from onset in MRI-selected patients with DWI-FLAIR mismatch?

Bottom Line

Intravenous tenecteplase within 4.5–24 hours of onset appeared safe and feasible in MRI-selected acute ischemic stroke patients, and was associated with significantly higher early neurological improvement compared to standard care, though no difference in 90-day functional outcomes was observed.

        Major Points
        80 patients with acute ischemic stroke were randomized to receive either intravenous tenecteplase (0.25 mg/kg) or standard care within 4.5–24 hours of onset based on MRI DWI-FLAIR mismatch.
Tenecteplase significantly improved early neurological improvement (27.5% vs 7.5%, P=0.03).
No significant difference in 90-day mRS 0–1 (52.5% vs 50%) or mRS 0–2 (65% vs 60%) between groups.
No symptomatic intracranial hemorrhage occurred; asymptomatic hemorrhagic transformation occurred in 7.5% of TNK group.
This is the first randomized trial of TNK in extended-window AIS using MRI-based selection.

      

Design

Study Type: Phase 2 randomized, open-label trial with blinded endpoint assessment

Randomization: 1

Blinding: Blinded endpoint assessors

Enrollment Period: March 2021 – July 2022

Follow-up Duration: 90 days

Centers: 14

Countries: China

Sample Size: 80

Analysis: Intention-to-treat; adjusted binary logistic regression for outcomes, including age, sex, SBP, NIHSS, ischemic stroke, and onset-to-randomization time as covariates; ordinal logistic regression and generalized linear models

Inclusion Criteria

Age 18–80 years
Acute ischemic stroke 4.5–24 hours from onset (including wake-up stroke)
NIHSS score 6–25
Pre-stroke mRS 0–1
MRI with DWI-FLAIR mismatch and infarct volume <70 mL
No hemorrhage on CT

Exclusion Criteria

Planned thrombectomy
Premorbid mRS ≥2
Contraindications to intravenous thrombolysis
Infarct involving >1/3 of MCA territory
Poor quality MRI
Uncontrolled hypertension

Baseline Characteristics

Age - TNK: 62.68 ± 8.87

Age - Control: 62.80 ± 8.56

Sex - Female: 22.5% (TNK), 35.0% (Control)

NIHSS Median: 7.5 (IQR 6.00–10.75) (TNK), 7.0 (IQR 6.00–8.75) (Control)

Hypertension: 60.0% (TNK), 70.0% (Control)

Wake-up stroke: 60.0% (TNK), 57.5% (Control)

Baseline infarct volume: 0.32 mL (IQR 0.00–2.28) (TNK), 0.40 mL (IQR 0.09–1.48) (Control)

Arms

Field	IV Tenecteplase	Control
Intervention	Single IV bolus of tenecteplase 0.25 mg/kg (max 25 mg) within 4.5–24 hours of onset	Standard care per acute ischemic stroke guidelines (antiplatelets, statins, BP/glucose control, supportive care)
Duration	Single dose, 90-day follow-up	90-day follow-up

Outcomes

Outcome	Type	Control	Intervention	HR / OR / RR	P-value
Proportion of patients with mRS 0–1 at 90 days	Primary	50.0% (20/40)	52.5% (21/40)		0.85
mRS 0–2 at 90 days	Secondary	60.0%	65.0%	1.44	0.50
Early Neurological Improvement (≥4 point NIHSS drop within 24h)	Secondary	7.5%	27.5%	5	0.03
Symptomatic Intracranial Hemorrhage	Adverse	0%	0%		>0.99
Asymptomatic Intracranial Hemorrhage	Adverse	0%	7.5% (3/40)		>0.99
Death at 14 days	Adverse	0%	0%		>0.99

Subgroup Analysis

No prespecified subgroup analysis reported; trial not powered for subgroup efficacy. ENI benefit consistent across groups but not statistically broken down.

Criticisms

Small sample size (n=80) limits statistical power to detect differences in functional outcomes
Open-label design may introduce bias despite blinded endpoint assessment
DWI-FLAIR mismatch alone may not capture all eligible late-window patients
Exclusion of patients planned for thrombectomy limits generalizability
Predominance of wake-up strokes (58.8%) may bias applicability to late-presenting known-onset strokes

Funding

Liaoning Province Science and Technology Project (2019JH2/10300027)

Based on: ROSE-TNK (Journal of Stroke, 2023)

Authors: Lu Wang, Ying-Jie Dai, Yu Cui, ..., Hui-Sheng Chen

Citation: J Stroke. 2023;25(3):371-377. doi:10.5853/jos.2023.00668

Content summarized and formatted by NeuroTrials.ai.

ROSE-TNK

(2023)

Objective

To evaluate the safety and feasibility of intravenous tenecteplase (TNK) for acute ischemic stroke patients treated 4.5–24 hours after onset, selected using MRI DWI-FLAIR mismatch.

Study Summary

• TNK within 4.5–24h was safe with no sICH events
• Early neurological improvement was significantly higher with TNK
• No difference in 90-day functional outcome (mRS 0–1: 52.5% vs 50%)

Intervention

Phase 2, randomized, open-label, blinded-endpoint study of IV TNK (0.25 mg/kg) vs standard care in MRI-selected stroke patients with DWI-FLAIR mismatch beyond 4.5h of onset.

Inclusion Criteria

• Age 18–80
• NIHSS 6–25
• mRS 0–1 before stroke
• Stroke onset 4.5–24h or wake-up stroke
• DWI-FLAIR mismatch with infarct <70 mL

Study Design

Arms: IV TNK vs Standard Medical Treatment

Patients per Arm: 40 TNK, 40 control

Outcome

• mRS 0–1 at 90d: 52.5% (TNK), 50% (control)
• ENI: 27.5% (TNK) vs 7.5% (control), p=0.03
• sICH: 0%; any ICH: 7.5% (TNK), 0% (control)

Bottom Line

Major Points

80 patients with acute ischemic stroke were randomized to receive either intravenous tenecteplase (0.25 mg/kg) or standard care within 4.5–24 hours of onset based on MRI DWI-FLAIR mismatch.
Tenecteplase significantly improved early neurological improvement (27.5% vs 7.5%, P=0.03).
No significant difference in 90-day mRS 0–1 (52.5% vs 50%) or mRS 0–2 (65% vs 60%) between groups.
No symptomatic intracranial hemorrhage occurred; asymptomatic hemorrhagic transformation occurred in 7.5% of TNK group.
This is the first randomized trial of TNK in extended-window AIS using MRI-based selection.

Study Design

Study Type: Phase 2 randomized, open-label trial with blinded endpoint assessment
Randomization: Yes
Blinding: Blinded endpoint assessors
Sample Size: 80
Follow-up: 90 days
Centers: 14
Countries: China

Primary Outcome

Definition: Proportion of patients with mRS 0–1 at 90 days

Control	Intervention	HR/OR	P-value
50.0% (20/40)	52.5% (21/40)	- (0.41–2.97)	0.85

Limitations & Criticisms

Small sample size (n=80) limits statistical power to detect differences in functional outcomes
Open-label design may introduce bias despite blinded endpoint assessment
DWI-FLAIR mismatch alone may not capture all eligible late-window patients
Exclusion of patients planned for thrombectomy limits generalizability
Predominance of wake-up strokes (58.8%) may bias applicability to late-presenting known-onset strokes

Citation

J Stroke. 2023;25(3):371-377. doi:10.5853/jos.2023.00668

View Original Publication →

ROSE-TNK

Intravenous Tenecteplase for Acute Ischemic Stroke Within 4.5–24 Hours of Onset (ROSE-TNK): A Phase 2, Randomized, Multicenter Study

Clinical Question

Bottom Line

Major Points

Design

Inclusion Criteria

Exclusion Criteria

Baseline Characteristics

Arms

Outcomes

Subgroup Analysis

Criticisms

Funding

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