Importance: The optimal dose, safety, and efficacy of intra-arterial tenecteplase after successful reperfusion by endovascular thrombectomy for large vessel occlusion (LVO) is unknown.Objective: To evaluate the dose-dependent adverse events and signals of efficacy of intra-arterial tenecteplase in LVO after successful reperfusion with thrombectomy, defined as an Extended Treatment in Cerebral Infarction score of 2b-3.Design, Setting, and Participants: This open-label, blinded-outcome assessment trial, incorporating a 14 + 8 dose-escalation (phase 1b, nonrandomized) and dose-expansion (phase 2a, randomized) design, was conducted in China between 2023 and 2024, with follow-up continuing through November 2024. This was a multicenter clinical trial including patients with LVO and successful reperfusion within 24 hours of last known well.Interventions: In phase 1b, intra-arterial tenecteplase, 0.0313, 0.0625, 0.1250, 0.1875 mg/kg; in phase 2a, intra-arterial tenecteplase 0.0313 or 0.0625 mg/kg, or control (without intra-arterial thrombolysis).Main Outcomes and Measures: The primary outcome in phase 1b was symptomatic intracranial hemorrhage (sICH) within 24 hours. The primary outcome in phase 2a was 90-day no-disability outcome (modified Rankin Scale score 0-1).Results: A total of 205 patients (phase 1b: 48, phase 2a: 157) were enrolled and analyzed. The median (IQR) age was 71 (60-77) years, and 113 (55.1%) were male. In phase 1b, 1 of 14 and 2 of 22 patients with sICH were observed at dose tiers 0.0313 and 0.0625 mg/kg, respectively. Three of 12 patients had sICH at dose tier 0.1250 mg/kg, exceeding the prespecified safety threshold (P = .04). In phase 2a, eligible patients were randomly assigned to receive tenecteplase, 0.0313 mg/kg (n = 46) and 0.0625 mg/kg (n = 46), and 65 patients composed the control group. The primary outcome occurred in 22 of 65 patients (33.8%) in the control group, 17 of 46 patients (37.0%) in the tenecteplase, 0.0313 mg/kg, group (adjusted risk ratio [RR] vs control, 0.85; 95% CI, 0.54-1.35; P = .50), and 20 of 46 patients (43.5%) in the tenecteplase, 0.0625 mg/kg, group (adjusted RR, 1.15; 95% CI, 0.73-1.80; P = .55). No significant difference in the safety outcomes was observed among the 3 groups.Conclusions and Relevance: Results of this phase 1 and 2 randomized clinical trial reveal that adjunctive intra-arterial tenecteplase dosages of 0.0313 mg/kg or 0.0625 mg/kg after successful reperfusion in patients with anterior circulation LVO showed adequate safety to advance to larger trials to determine the potential therapeutic benefits.Trial Registration: ChiCTR.org.cn Identifier: ChiCTR2300073787 and ChiCTR2400080624

Background: Among patients with acute ischemic stroke (AIS) secondary to large vessel occlusion (LVO) who undergo successful reperfusion following endovascular thrombectomy (EVT), only one-third are disability-free at 90 days, which may be related to persistent microvascular hypoperfusion after thrombectomy known as the “no-reflow phenomenon”. Adenosine is administered to prevent percutaneous coronary intervention (PCI)-related no-reflow through microvasculature dilation and neutrophil-mediated inflammation modulation. However, its role in in the setting of AIS has not been clearly elucidated. Objective: To evaluate the safety and efficacy of adjunctive intra-arterial adenosine following successful EVT in LVO patients. Methods and design: In this multicenter, open-label, randomized, phase 2 trial, we evaluated the safety and efficacy of adjunctive intra-arterial adenosine following successful EVT in AIS patients. Up to 160 eligible stroke patients with anterior intracranial large vessel occlusion presenting within 24 hours from symptom onset (time last known well) are planned to be consecutively randomized. The primary outcome was the shift in the distribution of mRS scores at 90 days. Safety outcomes included symptomatic intracranial hemorrhage (sICH) within 48 hours and mortality at 90 days. Discussions: This pivotal trial will provide first-hand data on the efficacy and safety of adjunctive intra-arterial adenosine following successful EVT in patients with acute ischemic stroke due to LVO. Trial registry number: ChiCTR2400092051 ( www.chictr.org.cn ).

This study aimed to examine the association between admission total serum calcium (Ca) levels and clinical outcomes in patients with large ischemic stroke

The optimal treatment strategy of Intracranial atherosclerotic disease-related large vessel occlusion (ICAD-LVO) remains undetermined. Current evaluation criteria focus on 90-day functional independence for acute-phase management, yet this timeframe does not represent the therapeutic endpoint given the persistent risk of recurrent stroke in this patient population. This study aims to examine whether stent angioplasty in patients with ICAD-LVO reduces long-term stroke recurrence risk while achieving successful vascular recanalization. In this retrospective cohort study of 131 ICAD-LVO patients (June 2022-January 2024), 65 underwent emergency stenting and 66 received nonstenting therapy. The primary outcome was 30-day to 1-year stroke recurrence, analyzed using competing risks regression (Fine-Gray model). Secondary outcomes included safety and 90-day functional status. The 1-year cumulative incidence of recurrence was 4.9% in the stent group versus 13.7% in the nonstent group (Gray's test, P = 0.088). After adjustment, stenting was significantly associated with a lower recurrence risk (subdistribution hazard ratio 0.19, 95% confidence interval 0.04-0.82; P = 0.026). A history of stroke/transient ischemic attack predicted higher risk (subdistribution hazard ratio 8.81, P = 0.002). Stenting was not associated with increased symptomatic intracranial hemorrhage, parenchymal hematoma type 2, 90-day mortality, or differences in 90-day functional independence. In this retrospective cohort study, emergency stent angioplasty was associated with a lower risk of 30-day to 1-year stroke recurrence in intracranial atherosclerotic occlusions and was not associated with an increased risk of procedural complications.

Background: Although successful recanalization of the occluded artery is achieved, no-reflow phenomenon (NRP) becomes a main contributor to poor prognosis in patients with acute ischemic stroke. There are some laboratory results to represent biomarkers of the no-reflow phenomenon. However, few studies have characterized the metabolomic signature of NRP. Using high-performance liquid chromatography–tandem mass spectrometry (LC–MS)-based method, this study aims to characterize the plasma metabolites associated with NRP. Methods: A total of 34 patients with acute large vessel occlusion in anterior circulation who underwent successful thrombectomy with final angiographic expanded Treatment in Cerebral Infarction score of 2c-3 score were enrolled (19 without NRP and 15 with NRP). Fasting venous blood collected 24 h after the procedure was centrifuged and subjected to metabolomic analysis. Results: We identified 29 differentially expressed plasma metabolites, the majority of which were phosphatidylcholine (PC) species. Among them, PC(20:4(5Z,8Z,11Z,14Z)/P-16:0) showed the most significant alteration and exhibited robust predictive performance (AUC = 0.846). The most prominently disrupted metabolic pathway was glycerophospholipid metabolism, particularly PC-mediated pathways, which appeared to play a central role in the association with of NRP. Conclusion: This study depict the plasma metabolic profile of NRP patients following stroke thrombectomy, and discover that phosphatidylcholine-dominated metabolites and related pathways may play a potential role in the occurrence of NRP. These metabolic biomarkers demonstrate promising discriminative ability and may help identify high-risk patients at an early stage, providing new targets for mechanism research and therapeutic intervention.

Background: Despite the high stroke burden in the elderly, their thrombolysis utilization is suboptimal partly due to heightened hemorrhagic risk. Observational data suggest that low-dose thrombolysis may offer comparable efficacy to standard-dose with a trend toward reduced symptomatic intracranial hemorrhage (sICH), yet high-level evidence for low-dose thrombolysis in this broad population remains absent. Objective: To evaluate the safety and efficacy of low-dose intravenous tenecteplase thrombolysis in elderly stroke patients within 4.5 hours of ischaemic stroke onset. Methods and design: The DATE-AGING trial is a multicenter, prospective, randomized, open-label, blinded-end point (PROBE) non-inferiority study. Eligible participants are elderly patients (aged ≥70 years) with acute ischemic stroke who meet current guideline recommendations for intravenous thrombolysis within 4.5 hours of symptom onset will be randomly assigned to Low-dose Tenecteplase group (0.175 mg/kg, max 17.5 mg) or Standard-dose Tenecteplase group (0.25 mg/kg, max 25 mg). The primary outcome is excellent functional outcome, defined as modified Rankin Scale(mRS) 0-1 at 90 days. Safety outcomes include sICH within 36 hours and mortality at 90 days. Discussions: The DATE-AGING trial is intended to provide high-quality evidence for low-dose tenecteplase intravenous thrombolysis in elderly patients with acute ischemic stroke. Trial registry number: NCT07294209.