Hamilton researchers from the Ontario Clinical Oncology Group (OCOG) – Thrombosis Division at the Juravinski Cancer Centre played a key role in a US-funded study that looked at the efficacy of pharmacomechanical catheter-directed thrombolysis (PCDT) for deep-vein thrombosis (DVT) patients. The ATTRACT Trial was sponsored by the National Heart Lung and Blood Institute (NHLBI) of the National Institutes of Health (NIH). Clinical research for this landmark study was conducted in 56 US hospitals while Hamilton’s OCOG researchers were responsible for trial methodology, data management, and data analysis. NIH-funded studies rarely involve research centres outside of the United States, so the Hamilton collaboration is noteworthy for a number of reasons.
“McMaster and HHS have a long tradition of doing venous thromboembolism research which is what prompted the US-Canadian collaboration that resulted in this study,” said the Data Coordinating Centre’s principal investigator, Clive Kearon, MD, a professor of medicine at McMaster University and a thromboembolism consultant at the Juravinski Hospital.
OCOG is an academic-based cancer and venous thrombosis clinical trial development and coordination organization. Researchers from Hamilton Health Sciences and McMaster University approach OCOG with research ideas that often lead to the design of local, provincial, national and international clinical trials. These trials are then conducted by the Data Coordinating Centre located at the Juravinski Hospital and Cancer Centre.
“The OCOG group played an important central role in the successful completion of this eight-year study,” said Jim Julian, OCOG associate director and ATTRACT co-investigator.
Final results of the trial were published in the current issue of The New England Journal of Medicine (NEJM), and are expected to affect policy in the United States and Canada. While a number of key findings were presented, the primary study results should dramatically reduce the use of an invasive procedure that is often used to treat deep-vein thrombosis in the United States, and head off expanded use of this procedure in Canada where it is much less often performed.
About 600,000 Americans have deep-vein thrombosis each year, roughly 300,000 of those are first time cases. Despite treatment with anticoagulant therapy, about 40% of DVT patients develop a long-term complication called post-thrombotic syndrome (PTS).
Patients who develop moderate-to-severe PTS experience major disability that can prevent them from walking, working, or conducting normal daily activities. Some patients develop painful open sores on the leg called “venous ulcers” that are difficult to heal.
Pharmacomechanical catheter-directed thrombolysis (“PCDT”) is an invasive treatment that removes blood clots using the clot-busting drug tissue plasminogen activator (TPA) delivered through a catheter that can also chew up the clots mechanically. The benefits and risks of PCDT have not before been evaluated for DVT treatment in a rigorous study.
Research Goals and Objectives:
To evaluate the benefits and risks of PCDT for the treatment of DVT; in particular, to determine if PCDT reduces the frequency and severity of the long-term complication of PTS, and the safety of the procedure in terms of major bleeding.
The trial randomly assigned 692 patients with acute proximal DVT to receive either anticoagulation alone (the control group) or PCDT in addition to anticoagulation. Participants were enrolled in 56 clinical centers in the United States and followed for two years. Outcomes included resolution of acute symptoms and signs, the frequency and severity of PTS, quality of life, bleeding and other procedure-related complications, and cost-effectiveness.
PCDT did not reduce the chance of developing PTS (47 vs. 48 percent of patients), but did reduce the severity of moderate to severe PTS (18 vs. 24 percent). The procedure also alleviated pain and swelling in the early stages of the disease. Major bleeding, however, was increased by PCDT (1.7 vs. 0.3 percent). Neither disease-specific or generic health-related quality of life differed between the two treatment groups.
For patients with acute proximal DVT, the addition of PCDT to anticoagulation did not result in a lower risk of post-thrombotic syndrome but did result in a higher risk of major bleeding. There was a hint, however, that PCDT’s benefits may outweigh risks in patients with exceptionally large clots.
Value / Study Impact :
Study results indicate that PCDT should rarely be used to treat DVT. Therefore, its use should be reduced in a setting where it is currently commonly performed, and should not be expanded in a setting where it is currently rarely performed (such as Hamilton and Canada generally).
The Acute Venous Thrombosis: Thrombus Removal with Adjunctive Catheter-Directed Thrombolysis (ATTRACT) Trial
Study start / end dates:
December 2009 / December 2016
Lead PI and PI for the Clinical Coordinating Centre: Dr. Suresh Vedantham, MD, Professor of Radiology and Surgery, Washington University School of Medicine,
Data Coordinating Centre PI at OCOG, Juravinski Hospital and Cancer Centre: Dr. Clive Kearon, MD, Jack Hirsh Professor in Thromboembolism, Professor of Medicine at McMaster University, and consultant in Clinical Thromboembolism at the Juravinski Hospital in Hamilton
Jim Julian (chief statistician and co-investigator); Chu-Shu Gu (biostatistician); Sameer Parpia (biostatistician); Marc Filion (study coordinator); Lucy Spadafora (adjudication coordinator); Erin McGean (data management assistant); Donna McCarty (research administrator)
The ATTRACT Trial was supported by the National Heart, Lung and Blood Institute of the National Institutes of Health (NIH), with separate grants for the CCC (PI; Dr.Vedantham) and the DCC (PI; Dr.Kearon). Additional funding was provided by Boston Scientific, Covidien (now Medtronic), and by Genentech (a Roche Company). Study drug was provided by Genentech and compression stockings were donated by BSN Medical.
More information / contact:
Dr. Clive Kearon (firstname.lastname@example.org)
For full protocol, please see Supplemental Material at NEJM link.