Ultrasound Accelerated Catheter-directed Thrombolysis for Primary Iliofemoral Deep Vein Thrombosis (IFDVT) Compared to Non-invasive Conventional Anticoagulant Therapy Alone: a Dutch Randomized Controlled Multicenter Clinical Trial

Rationale: Iliofemoral deep venous thrombosis (IFDVT) is associated with significant post thrombotic morbidity. The presence of both obstruction and reflux significantly increases the chances for development of post-thrombotic syndrome (PTS). Early thrombolysis may reduce the incidence of PTS as compared to treatment with conventional anticoagulant medication alone. Improvement of the health related quality of life (HRQOL) has been reported after surgical clot removal. The investigators hypothesize that such improvements could also be reached after catheter-directed thrombolysis (CDT).

Objective: To assess whether CDT for the treatment of IFDVT can safely and effectively reduce post-thrombotic morbidity after one year. The secondary objective is to study whether CDT intervention has a positive effect on the HRQOL of patients with IFDVT and to assess late PTS.

Study design: Prospective, multicenter, single-blind, allocation concealed, randomized controlled trial Study population: All consecutive patients with IFDVT presenting at the emergency or outpatient departments of the participating centers. The thrombus should not be older than 14 days at randomization.

Intervention: After randomization patients will be allocated to either conservative anticoagulant treatment or to CDT combined with conservative anticoagulant treatment.

Main study parameters/endpoints: The primary efficacy outcome is the proportion of PTS at one year; a decline in PTS incidence from 25% to 8% is anticipated. The secondary outcome is the Health related Quality of life. The principal safety outcome is major bleeding during anticoagulant therapy. Bleeding as well as events of recurrent thrombosis will be monitored. Measurements of markers of coagulation and inflammation will be performed during follow-up. After CDT the patency of the venous system in the affected lower limb will be assessed as well as the percentage of clot lysis. The development of late PTS during follow-up will also be monitored.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: For patients who are randomized to CDT a hospital stay for 24-96 hours is mandatory. All patients will undergo additional imaging by magnetic resonance venography and air phletysmography (if available) at baseline and after 12 months; blood will be taken at these visits. Clinical follow-up visits will be matching usual care at 3, 6, 12 months. Health-related quality of life (HRQOL) questionnaires will be filled out by all patients at baseline, 3, 6 and 12 months after the event; and once a year during the entire study duration. Further treatment will be in accordance with current guidelines for antithrombotic treatment. There may be an enhanced risk of bleeding in the thrombolysis group. The expected benefit is reduction of PTS from 25% to 8%, together with an improved quality of life.