by Pauline T. Mayer
Ultrasound-accelerated catheter directed thrombolysis is state-of-the art technology for treatment of deep venous thrombosis (DVT) and particularly iliofemoral DVT. The technology was engineered in the United States by EKOS corporation located in Bothel, Washington. It is the only endovascular system that can deliver ultrasonic microsonic energy and thrombolytic drugs simultaneously, which many experts agree is safer, faster and a more complete way to remove clots by emphasizing accelerating dissolution. The EKOS device is four times faster than conventional catheter-directed thrombolysis with no evidence of thrombus breakage or hemolysis. Vein Magazine has learned that vascular surgeons worldwide are utilizing the EKOS technology for the treatment of iliofemoral deep venous thrombosis. A new trial, known as the cAVA-trial: cAtheter Versus Anticoagulation Alone For Acute Primary (ilio) Femoral DVT is actively underway in Europe.
In a telephone interview with Dr. cees Wittens, a vascular surgeon from Maastricht University Medical centre, Maastricht, the Netherlands, and one of the lead principals in this study, Dr. Wittens provided background on the DUTcH cAVA-trial. Following are Dr. Wittens’ responses in which he elaborates on the objectives, patient eligibility, timing and technology pertaining to this trial.
Pauline Mayer: Q: Dr. Wittens, who are the principal investigators behind the trial?
Dr. Wittens: A: First and foremost, thank you for giving me this opportunity to provide the Vein Magazine readership with information on the DUTcH cAVA-trial. In addition to myself, Professor Dr. H. Ten cate, a noted specialist in internal medicine and hematology, serve as principal investigators. The trial is managed from Maastricht University Medical centre in the Netherlands.
Q: When did the trial commence and how long is it expected to run?
Dr. Wittens: A: The trial commenced on July 2, 2010 and the expected primary outcome evaluation will occur the end of 2013.
Q: How many sites have been designated to conduct this study?
Dr. Wittens: A: In addition to Maastricht University Medical centre, there are eight participating Dutch centers in the Netherlands. All local investigators are specialists in internal medicine and hematology. Local investigators and sites include: Drs. A. Jie and g. Mostard of Atrium Medical centre, Heerlen, Dr. M. van de Poel, Laurentius Hospital, Roermond, Drs. A. Koster and E. Bouwmans, Viecuri Medical centre, Venlo-Venray, Dr. A. Stork,
St. Anna Hospital, geldrop, Drs. M. Nijziel and L. Tick, Máxima Medical centre, Eindhoven-Veldhoven, Dr. W. Peters, catharina-Hospital, Eindhoven, and Dr. E. Jacobs, Elkerliek Hospital, Helmond.
Q: Dr. Wittens, in your own personal opinon, why is the trial necessary?
Dr. Wittens: A: No doubt an excellent question. Iliofemoral deep ve-nous thrombosis (IFDVT) is associated with signifi-cant post throm-botic morbidity referred to as post thrombotic syndrome (PTS).
The presence of both obstruction and reflux significantly in-creases the chances for development of PTS. Early thrombolysis may reduce the incidence of PTS as compared to treatment with standard anticoagulant therapy alone. Improvement of the health-related quality of life (HR-QOL) has been reported after surgical clot removal. We hypothesize that such improvements could also be reached after ultrasound-accelerated catheter-
directed thrombolysis.
Q: Let’s address objectives. What is the first objective of the DUTCH CAVA-trial?
Dr. Wittens: A: The primary objective of the DUTcH cAVA-trial is to assess whether ultrasound-accelerated catheter directed thrombolysis combined with standard anticoagulant and compression therapy (intervention group, arm 1) in acute primary IFDVT can significantly reduce the PTS incidence after one year compared with standard anticoagulant and compression therapy alone (control group, arm 2).
Q: And the second objective?
Dr. Wittens: A: The secondary objective is to investigate the effects on clot lysis, patency of the affected vein, valve function, recurrent thrombosis rate, HR-QOL and medical costs.
Q: What about patient eligibility?
Dr. Wittens: A: All eligible cAVA-trial patients are 18-85 years old.
Q: How many patients are currently enrolled in the trial?
Dr. Wittens: A: currently (as of 8/14/2010) there are 5 patients enrolled in the cAVA-trial. We hope to enroll 180 patients (90 patients per arm) by the end of 2012. The follow-up for evaluation of the primary outcome (1-year PTS incidence) is 1 year.
Q: How do you see ultrasound-assisted thrombolysis as being the best therapy for the treatment of IFDVT?
Dr. Wittens: A: Ultrasound-accelerated thrombolysis functions as a catalyst to catheter directed thrombolysis, reducing the median Urokinase infusion time by more than 50% and the mean total Urokinase dose by nearly 75%. Furthermore, the complete clot lysis rates are promising (over 80%) with ultrasound-accelerated catheter directed thrombolysis. What is significant is that the bleeding rates are very low (around 3%, equal to standard oral anticoagulant therapy) with no thrombo-embolic events observed so far.
Q: What about the future?
Dr. Wittens: A In conclusion, ultrasound-accelerated catheter directed thrombolysis may be a safe and promising candidate for front line therapy in DVT, having the benefits of thrombolysis and minimizing the potential side effects. However, large RcTs (like the cAVA-trial) are needed to confirm its superiority over standard cDT and elucidate whether or not ultrasound accelerated catheter directed thrombolysis can also effectively prevent PTS, improve quality of life and reduce costs.
