Intra-arterial tenecteplase after successful endovascular recanalisation in patients with acute posterior circulation arterial occlusion (ATTENTION-IA): multicentre randomised controlled trial

Abstract

Objective: To assess whether intra-arterial tenecteplase administered after successful endovascular recanalisation improves outcomes in patients with acute arterial occlusion of the posterior circulation.

Design: Multicentre randomised controlled trial.

Setting: 31 hospitals in China, 24 January 2023 to 24 August 2023.

Participants: 208 patients with successful recanalisation (grade 2b50-3 on the extended thrombolysis in cerebral infarction scale) of an occlusion in the V4 segment of the vertebral artery; proximal, middle, or distal segment of the basilar artery; or P1 segment of the posterior cerebral artery: 104 were randomly allocated to receive tenecteplase and 104 to receive standard care.

Interventions: Intra-arterial tenecteplase (0.0625 mg/kg, maximum dose 6.25 mg) administered proximal to the residual thrombus (if still present) or distal to the origin of the main pontine perforator branches over 15 seconds, or endovascular treatment only (control group).

Main outcome measures: The primary outcome was freedom from disability (modified Rankin scale score 0 or 1) at 90 days after randomisation. Primary safety outcomes included symptomatic intracranial haemorrhage within 36 hours and all cause mortality at 90 days. All efficacy and safety analyses were conducted by intention to treat and adjusted for age, pre-stroke modified Rankin scale score, time from onset of moderate to severe stroke (National Institutes of Health stroke scale score ≥6) to randomisation, hypertension, and baseline stroke severity.

Results: At 90 days, 36 patients (34.6%) in the tenecteplase group and 27 (26.0%) in the control group had a modified Rankin scale score of 0 or 1 (adjusted risk ratio 1.36, 95% confidence interval 0.92 to 2.02; P=0.12). Mortality at 90 days was similar between the tenecteplase and control groups: 29 (27.9%) v 28 (26.9%), adjusted risk ratio 1.13, 0.73 to 1.74. Symptomatic intracranial haemorrhage within 36 hours occurred in eight patients (8.3%) in the tenecteplase group and three (3.1%) in the control group (adjusted risk ratio 3.09, 0.78 to 12.20).

Conclusions: In patients with acute ischaemic stroke due to acute posterior large or proximal vessel occlusion, intra-arterial tenecteplase administered after successful recanalisation was not associated with a statistically significant reduction in combined disability and mortality at 90 days.

Trial registration: ClinicalTrials.gov NCT05684172.

Fig 1

Trial profile of patients randomly assigned in a 1:1 ratio to receive either endovascular treatment plus intra-arterial tenecteplase (tenecteplase group) or endovascular treatment only (control group)

Fig 2

Distribution of modified Rankin scale scores (functional outcomes) at 90 days in intention-to-treat population (no patients lost to follow-up). Scores range from 0 to 6: 0=no symptoms; 1=no clinically important disability; 2=slight disability (patients can look after themselves without assistance but are not able to carry out previous activities); 3=moderate disability (patients require some help but are able to walk unassisted); 4=moderately severe disability (patients are unable to attend to bodily needs without assistance and are unable to walk unassisted); 5=severe disability (patients require constant nursing care and attention); and 6=death

Fig 3

Subgroup analyses of modified Rankin scale scores of 0 or 1 at 90 days (primary outcome). The trial had no prespecified correction for multiple comparisons for a definitive analysis of subgroups. CI=confidence interval; CT=computed tomography; eTICI=extended thrombolysis in cerebral infarction; NIHSS=National Institutes of Health stroke scale; pc-ASPECTS=posterior circulation-acute stroke prognosis early CT score