A similar effect of fibrinogen on efficacy and safety of tenecteplase alteplase in acute ischemic cerebrovascular events (TRACE II) trial.

Background And Objectives: Hemostasis factors affecting clot patterns, particularly fibrinogen, may influence the effectiveness of intravenous thrombolysis (IVT). We aimed to investigate the impact of differences in fibrinogen plasma levels on the efficacy and safety of tenecteplase alteplase in an acute ischemic cerebrovascular events-II (TRACE-II) trial.

Methods: In a multi-center, prospective, open-label, end-point blinded, randomized, controlled trial. Adults with acute ischemic stroke (AIS) were enrolled. Patients received intravenous tenecteplase (0-25 mg/kg) or alteplase (0-9 mg/kg) within 4-5 h. Patients were divided into three groups according to their plasma fibrinogen level: low fibrinogen level (< 2 g/L), normal fibrinogen level (2-4 g/L), and high fibrinogen level (> 4 g/L). The Modified Rankin Score (mRS) from 2 to 6 was used to define the efficacy outcome. The safety outcomes were the occurrence of symptomatic intracranial hemorrhage (sICH) within 36 h and 90 days, parenchymal hematoma 2 (PH) within 36 h, any intracranial hemorrhage (ICH), other significant hemorrhagic events, and death at 3 months. SAS software version 9.4 was used for statistical analysis. Binary logistic regression was used to evaluate the efficacy and safety outcomes differences between tenecteplase and alteplase in the three fibrinogen groups. The interaction between treatment and fibrinogen subgroups was used to assess the effect of fibrinogen levels on the efficacy and safety of different treatments. All -values are two-tailed and significance was defined as < 0.05.

Results: The trial enrolled 1409 patients with AIS. Among them, 705 patients received tenecteplase treatment and 704 patients received alteplase treatment. Six percent of all patients had a low plasma fibrinogen level ( < 2 g/L), 81% had a normal fibrinogen level (2-4 g/L), and 13% had a high plasma fibrinogen level ( > 4 g/L). The efficacy of tenecteplase compared to alteplase remained consistent across varying fibrinogen levels (interaction = 0.30). Additionally, the safety outcomes were comparable between the two treatments across all fibrinogen levels [sICH at 36 h (interaction = 0.94); sICH at 90 days (interaction = 0.77); PHICH at 36 h (interaction = 0.84); Other symptomatic hemorrhagic events within 90 days (interaction = 0.54)]. Similarly, there was no significant difference in mortality rates between patients treated with tenecteplase and alteplase across different plasma fibrinogen levels (interaction = 0.58).

Conclusion: The results of the study suggest that the efficacy and safety of tenecteplase in treated AIS patients within 4.5 h are comparable to those of alteplase, regardless of plasma fibrinogen levels.