CAVA (Ultrasound‐Accelerated Catheter‐Directed Thrombolysis on Preventing Post‐Thrombotic Syndrome) Trial: Long‐Term Follow‐Up Results

Background The CAVA (Ultrasound‐Accelerated Catheter‐Directed Thrombolysis Versus Anticoagulation for the Prevention of Post‐Thrombotic Syndrome) trial did not show a reduction of post‐thrombotic syndrome (PTS) after additional ultrasound‐accelerated catheter‐directed thrombolysis in patients with acute iliofemoral deep vein thrombosis at 1‐year follow‐up. This prespecified analysis of the CAVA trial aimed to determine the impact of additional thrombolysis on outcomes of PTS at long‐term follow‐up. Methods and Results Patients aged 18 to 85 years with a first‐time acute iliofemoral deep vein thrombosis were included and randomly assigned (1:1) to either standard treatment plus ultrasound‐accelerated catheter‐directed thrombolysis or standard treatment alone. The primary outcome was the proportion of PTS (Villalta score ≥5 on 2 occasions ≥3 months apart or venous ulceration) at the final follow‐up visit. Additionally, PTS according to the International Society on Thrombosis and Haemostasis (ISTH) consensus definition was assessed to allow external comparability. Major bleedings were the main safety outcome. At a median follow‐up of 39.0 months (interquartile range, 23.3–63.8), 120 patients (79.8%) participated in the final follow‐up visit: 62 from the intervention group and 58 from the standard treatment group. PTS developed in 19 (30.6%) versus 26 (44.8%) patients, respectively (odds ratio [OR], 0.54; 95% CI, 0.26 to 1.15 [P=0.11]), with an absolute difference between groups of −14.2% (95% CI, −32.0% to 4.8%). Using the ISTH consensus definition, a significant reduction in PTS was observed (29 [46.8%] versus 40 [69.0%]) (OR, 0.40; 95% CI, 0.19–0.84 [P=0.01]) with an absolute difference between groups of −22.2% (95% CI, −39.8% to −2.8%). No new major bleedings occurred following the 12‐month follow‐up. Conclusions The impact of additional ultrasound‐accelerated catheter‐directed thrombolysis on the prevention of PTS was found to increase with time. Although this study was limited by its sample size, the overall findings indicate a reduction of mild PTS without impact on quality of life. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT00970619