Improved Functional Outcome After Additional Catheter-Directed Thrombolysis for Acute Iliofemoral Deep Vein Thrombosis: Results of a Randomized Controlled Clinical Trial (The CaVenT Study)

Abstract

Abstract LBA-1 Background: Following acute deep vein thrombosis (DVT) of the lower limb, approximately 1 in 4 patients treated with anticoagulation (AC) and elastic compression stockings (ECS) in accordance with current guidelines, are still at risk for developing a chronically reduced functional outcome, i.e., the post-thrombotic syndrome (PTS). Additional treatment with catheter-directed thrombolysis (CDT) enhances clot removal and is suggested to favor venous competence and patency, thereby reducing the risk for PTS. This interventional therapy is expensive, associated with life-threatening bleeding, and converts an outpatient disease to an inpatient disease. However, it has become standard care in some centers despite a complete lack of evidence from randomized, controlled trials (RCT). The CaVenT study, representing the first RCT in this area, aimed to evaluate whether additional CDT with alteplase improved the functional outcome by reducing PTS development following acute iliofemoral DVT. Methods: The CaVenT study was an open, multicenter RCT that recruited patients from 20 hospitals in the Norwegian south-eastern health region. Patients of age 18–75 years with a first-time objectively verified acute iliofemoral DVT above mid-thigh level and symptoms for up to 21 days were eligible for recruitment. Study patients were randomly assigned with a 1:1 ratio to standard (control) treatment with AC and ECS grade II (30 mmHg) or to CDT with alteplase in addition to standard treatment. The present report concerns the primary clinical end-point; the frequency of PTS after 24 months follow-up. The study was designed to detect a reduction in PTS from 25% to 10% with a 5% significance level and with 80% power. Follow-up visits were conducted at 6 months ± 2 weeks and 24 months ± 4 weeks and included evaluation of PTS by the Villalta scale as recommended by the International Society on Thrombosis and Haemostasis. Iliofemoral patency was assessed with ultrasonography and air-plethysmography. A two-sided uncorrected Chi-square test was used for comparing dichotomous variables in the two treatment groups. Results: 209 patients with acute iliofemoral DVT were randomized during 2006–2009; 101 patients were allocated the CDT arm and 108 the control arm. At the completion of 24 months follow-up, data on clinical status were available and included in the intention to treat analyzes for 90 patients in the CDT arm and 99 control patients. Mean age was 51.5 years (SD 15.8), 36% were female, and mean duration of symptoms was 6.6 days (SD 4.6). 80/90 patients receiving CDT had successful lysis. At 24 months follow-up 37 (41.1%, 95% CI 31.5–51.4%) allocated additional CDT presented with PTS compared to 55 (55.6%, 95% CI 45.7–65.0%) in the control group (p=0.047), including one control with severe PTS. The difference in PTS corresponds to an absolute risk reduction of 14.4% (95% CI 0.2–27.9), and the number needed to treat was 7 (95% CI 4–502). No patients presented with venous ulcer. In total 20 bleeding complications were reported; 3 were classified as major and 5 as clinically relevant. The majority of bleedings were related to the puncture site. The major bleedings included 1 abdominal wall hematoma requiring blood transfusion, 1 compartment syndrome of the calf requiring surgery, and 1 inguinal puncture site hematoma. No bleeding led to a permanently reduced outcome, and there were no deaths, pulmonary embolism or cerebral hemorrhage related to CDT. Patients who had regained venous patency after 6 months, developed PTS in 38/103 (36.9%, 95% CI 28.2–46.5%) as compared to 49/80 (61.3%, 95% CI 50.3–71.2%) of patients with insufficient recanalization (p<0.001). During follow-up 28 patients experienced recurrent venous thromboembolism and 11 were diagnosed with cancer; the differences were not statistically significant between the two treatment groups. Conclusion: Additional CDT with alteplase significantly reduced the rate of PTS compared to standard treatment alone. CDT resulted in successful lysis in the great majority of patients with iliofemoral DVT. However, it also entailed an additional risk of bleeding, emphasizing the importance of patient selection and safely performed CDT procedures. Overall this first RCT on the efficacy and safety of CDT suggests a net clinical benefit of additional CDT. Our findings have implications for update of guidelines, and CDT should be considered in patients with upper femoral or iliac DVT. Disclosures: No relevant conflicts of interest to declare.