← Back

ANGEL-TNK

Intra-arterial Tenecteplase for Acute Stroke After Successful Endovascular Therapy

Share Share Copied! Compare

Year of Publication: 2025

Authors: Zhongrong Miao, PhD; Gang Luo, PhD; Ligang Song, ..., PhD; for the ANGEL-TNK Investigators

Journal: JAMA

Citation: JAMA. 2025;334(7):582-591. doi:10.1001/jama.2025.10800

Link: https://jamanetwork.com/journals/jama/fullarticle/2823104

Clinical Question

Does intra-arterial tenecteplase after successful thrombectomy improve clinical outcomes in patients with acute large vessel occlusion presenting between 4.5 and 24 hours after symptom onset?

Bottom Line

In patients with acute LVO presenting between 4.5 and 24 hours of symptom onset, intra-arterial tenecteplase after successful thrombectomy had a greater likelihood of excellent neurological outcome at 90 days without increasing the risk of symptomatic ICH or mortality.

        Major Points
        Prospective, open-label, blinded end point, randomized trial across 19 centers in China
Primary outcome of excellent neurological function (mRS 0-1) at 90 days was significantly higher with tenecteplase (40.5% vs 26.4%, RR 1.44, P = 0.02)
Secondary efficacy outcomes did not show statistically significant differences between groups
No increase in symptomatic intracranial hemorrhage (5.6% vs 6.2%) or 90-day mortality (21.4% vs 21.7%)
Patients with higher blood glucose levels (≥100 mg/dL) showed greater benefit from tenecteplase (interaction effect P = 0.02)
Follow-up angiography showed improved eTICI scores after intra-arterial thrombolysis

      

Design

Study Type: Prospective, open-label, blinded end point, randomized clinical trial

Randomization: 1

Blinding: Open-label with blinded end point assessment (mRS scores assessed by neurologists unaware of treatment assignment)

Enrollment Period: February 16, 2023 to March 23, 2024

Follow-up Duration: 90 days with final follow-up on July 4, 2024

Centers: 19

Countries: China

Sample Size: 256

Analysis: Intention-to-treat analysis using generalized linear model with log link and binomial error distribution, performed with SAS version 9.4

Inclusion Criteria

Age 18 years or older
Time last known well to randomization of 4.5 to 24 hours
NIHSS score ≥2
Prestroke mRS score of 0 or 1
Intracranial occlusion of ICA, M1, or dominant M2 segment on CTA or MRA
ASPECTS ≥6 on non-contrast CT or DWI
Ischemic infarct core <70 mL
Mismatch ratio ≥1.2 and mismatch volume ≥10 mL on CT/MR perfusion
Successful endovascular therapy (eTICI 2b50 to 3)

Exclusion Criteria

Received intravenous thrombolysis on admission
Received intravenous heparin during treatment
Would likely require antiplatelet therapy within first 24 hours after endovascular treatment
Midline shift or clinical signs of herniation
Mass effect or high risk of hemorrhage
Acute bilateral strokes
Multiple intracranial occlusions

Baseline Characteristics

Characteristic	Control	Active
Age - Median (IQR)	71.7 (61.7-79.0) years	71.5 (60.6-79.5) years
Sex - Female	43.4%	46.0%
Sex - Male	56.6%	54.0%
Stroke classification - Cardioembolic	64.3%	70.6%
Stroke classification - Atherothrombotic	28.7%	23.8%
Baseline mRS score of 1	8.5%	6.3%
NIHSS at admission - Median (IQR)	16 (12-19)	15 (12-19)
Occlusion site - ICA	29.5%	26.2%
Occlusion site - M1	49.6%	46.0%
Occlusion site - M2	20.9%	27.8%
ASPECTS - Median (IQR)	7.00 (6.00-8.00)	7.00 (6.00-8.00)
Baseline infarct volume - Median (IQR)	18.10 (4.30-51.00) mL	19.83 (3.80-39.90) mL
Time onset to randomization - Median (IQR)	9.5 (6.9-13.0) hours	9.31 (6.7-13.5) hours

Arms

Field	Control	Intra-arterial Tenecteplase
Intervention	Standard medical management according to Chinese Stroke Association guidelines with additional control follow-up angiography	Recombinant human tenecteplase (rhTNK-tPA) 0.125 mg/kg (maximum 12.5 mg) infused slowly over 15 minutes through microcatheter in horizontal segment of MCA distal to lenticulostriate branches
Duration	Through 90-day follow-up	Single administration after successful endovascular therapy

Outcomes

Outcome	Type	Control	Intervention	HR / OR / RR	P-value
Excellent outcome at 90 days, defined as modified Rankin Scale (mRS) score of 0 to 1	Primary	34/129 (26.4%)	51/126 (40.5%)	8	0.02
mRS score at 90 days (shift analysis)	Secondary	Median 3 (1-4)	Median 3 (1-5)		0.41
mRS score of 0-2 at 90 days	Secondary	60/129 (46.5%)	58/126 (46.0%)		0.63
mRS score of 0-3 at 90 days	Secondary	72/129 (55.8%)	67/126 (53.2%)		0.45
NIHSS 0-1 or improved ≥10 points at 36 hours	Secondary	20/129 (15.5%)	17/126 (13.5%)		0.49
European Quality of Life Visual Analogue Scale at 90 days	Secondary	Median 70.00 (25.00-90.00)	Median 75.00 (40.00-95.00)		0.38
Time to maximum volume >6 s at 24 hours	Secondary	Median 4.50 (0.00-46.20)	Median 0.00 (0.00-28.70)		0.42
Infarct core volume change from baseline	Secondary	Median -8.00 (-28.50 to 0.00)	Median -11.30 (-37.00 to 0.00)		0.94
Symptomatic intracranial hemorrhage within 48 hours	Adverse	8/129 (6.2%)	7/126 (5.6%)		0.92
Any intracranial hemorrhage within 48 hours	Adverse	36/129 (27.9%)	31/126 (24.6%)		0.63
Death within 90 days	Adverse	28/129 (21.7%)	27/126 (21.4%)		0.78

Subgroup Analysis

Significant interaction found with admission glucose levels: patients with glucose ≥100 mg/dL showed greater benefit from tenecteplase (RR 1.82, P<0.001) compared to those with glucose <100 mg/dL (RR 0.59, P=0.23); interaction P=0.02. Other prespecified subgroups showed no significant interactions.

Criticisms

Trial excluded patients who received IV thrombolysis, periprocedural IV heparin, or antiplatelet use, limiting generalizability
Open-label design may introduce bias despite blinded endpoint assessment
Single country (China) study limits external validity
Secondary efficacy endpoints did not support the primary finding
Dose of intra-arterial tenecteplase was empirically chosen based on previous experience
Population was primarily cardioembolic stroke patients due to exclusion criteria
Small sample size for some subgroup analyses

Funding

China Shijiazhuang Pharmaceutical Company Recomgen Pharmaceutical (Guangzhou) Co Ltd. provided tenecteplase and an unrestricted research grant to support trial infrastructure

Based on: ANGEL-TNK (JAMA, 2025)

Authors: Zhongrong Miao, PhD; Gang Luo, PhD; Ligang Song, ..., PhD; for the ANGEL-TNK Investigators

Citation: JAMA. 2025;334(7):582-591. doi:10.1001/jama.2025.10800

Content summarized and formatted by NeuroTrials.ai.

ANGEL-TNK

(2025)

Objective

To assess the efficacy and safety of intra-arterial tenecteplase after successful thrombectomy in patients with anterior circulation LVO presenting 4.5–24 hours from last known well.

Study Summary

• Intra-arterial tenecteplase (TNK) administered after successful thrombectomy increased the rate of excellent outcomes (mRS 0–1 at 90 days) compared to standard care without lytics. • No significant increase in bleeding or mortality was observed.

Intervention

Intra-arterial tenecteplase 0.125 mg/kg (max 12.5 mg) over 15 minutes post-thrombectomy vs no IA thrombolytics (standard care).

Inclusion Criteria

Patients with anterior circulation LVO, 4.5–24 hours from LKW, eTICI 2b50–3 reperfusion after thrombectomy. Excluded if received intravenous thrombolysis on admission, received intravenous heparin during treatment, or would likely require antiplatelet therapy within the first 24 hours after endovascular treatment.

Study Design

Arms: IA Tenecteplase vs Standard Medical Treatment (no lytic)

Patients per Arm: 126 IA tenecteplase vs 129 standard medical treatment (256 randomized, 255 in full analysis); mRS 0–1: 40.5% vs 26.4%

Outcome

• mRS 0–1 at 90 days: 40.5% vs 26.4% (RR 1.44, 95% CI 1.06–1.95, P = 0.02).<br>• sICH within 48h: 5.6% vs 6.2%.<br>• Any ICH: 24.6% vs 27.9%.<br>• 90-day mortality: 21.4% vs 21.7% (NS for all safety outcomes).

Bottom Line

Major Points

Prospective, open-label, blinded end point, randomized trial across 19 centers in China
Primary outcome of excellent neurological function (mRS 0-1) at 90 days was significantly higher with tenecteplase (40.5% vs 26.4%, RR 1.44, P = 0.02)
Secondary efficacy outcomes did not show statistically significant differences between groups
No increase in symptomatic intracranial hemorrhage (5.6% vs 6.2%) or 90-day mortality (21.4% vs 21.7%)
Patients with higher blood glucose levels (≥100 mg/dL) showed greater benefit from tenecteplase (interaction effect P = 0.02)
Follow-up angiography showed improved eTICI scores after intra-arterial thrombolysis

Study Design

Study Type: Prospective, open-label, blinded end point, randomized clinical trial
Randomization: Yes
Blinding: Open-label with blinded end point assessment (mRS scores assessed by neurologists unaware of treatment assignment)
Sample Size: 256
Follow-up: 90 days with final follow-up on July 4, 2024
Centers: 19
Countries: China

Primary Outcome

Definition: Excellent outcome at 90 days, defined as modified Rankin Scale (mRS) score of 0 to 1

Control	Intervention	HR/OR	P-value
34/129 (26.4%)	51/126 (40.5%)	- (1.06-1.95)	0.02

Limitations & Criticisms

Trial excluded patients who received IV thrombolysis, periprocedural IV heparin, or antiplatelet use, limiting generalizability
Open-label design may introduce bias despite blinded endpoint assessment
Single country (China) study limits external validity
Secondary efficacy endpoints did not support the primary finding
Dose of intra-arterial tenecteplase was empirically chosen based on previous experience
Population was primarily cardioembolic stroke patients due to exclusion criteria
Small sample size for some subgroup analyses

Citation

JAMA. 2025;334(7):582-591. doi:10.1001/jama.2025.10800

View Original Publication →

ANGEL-TNK

Intra-arterial Tenecteplase for Acute Stroke After Successful Endovascular Therapy

Clinical Question

Bottom Line

Major Points

Design

Inclusion Criteria

Exclusion Criteria

Baseline Characteristics

Arms

Outcomes

Subgroup Analysis

Criticisms

Funding

Ask about ANGEL-TNK