In 2018, Suresh Vedantham, MD, FSIR, of the Mallinckrodt Institute of Radiology, Washington University in St. Louis, received funding from the National Heart, Lung and Blood Institute (NHLBI) of the National Institutes of Health (NIH) to lead a multicenter, randomized trial called Chronic Venous Thrombosis: Relief with Adjunctive Catheter-directed Therapy (C-TRACT). For this trial, 20–40 clinical centers will be recruited with plans to enroll approximately 374 subjects. SIR Foundation encourages SIR members to participate in this important effort to support evidence-based IR care by serving as site investigators or by referring patients to study sites.
We recently sat down with Dr. Vedantham to discuss C-TRACT and its potential for IR.
What is C-TRACT and what was it designed to study?
The C-TRACT clinical trial is a recently started, pivotal, NIH-sponsored, multicenter randomized trial that is evaluating the effects of endovascular therapy (iliac vein stenting followed by saphenous ablation) on patients with established, moderate-to-severe post-thrombotic syndrome (PTS). The study is designed to determine if the use of endovascular therapy reduces the clinical severity of PTS and improves quality of life, compared with standard PTS care without endovascular therapy.
What does C-TRACT expect to find?
We expect to characterize the risk-benefit ratio and cost-effectiveness of endovascular therapy. We don’t know how that will look, which justifies conducting a randomized trial. As an IR who has performed these procedures for many years, my personal bias is to believe that we will see at least a short-term benefit (reduction in PTS severity) with use of endovascular therapy.
But physicians with different backgrounds and experiences may reasonably believe otherwise. However good we may feel about our own experiences, how certain can we be that getting a chronically occluded iliac vein open is generalizable to a larger range of providers? How do we know the vein will stay open, given the strong proclivity of PTS patients towards recurrent thrombosis? Projecting in the long term is difficult. I doubt we will see major safety issues. Cost-effectiveness will depend on the extent of the treatment effect—it will need to be robust and sustained to outweigh the assuredly high costs of endovascular treatment.
Why is this trial important?
First and foremost, many thousands of patients suffer from PTS without effective treatment. The ATTRACT Trial showed that preventing PTS is not straightforward and that mechanisms beyond “open veins” must be involved—so patients will continue to contend with this condition for the foreseeable future.
Although IRs have delivered endovascular therapy to PTS patients for years, there are no high-quality studies and there are important concerns about long-term effectiveness. For example, studies suggest that more than one-third of stented PTS patients will experience recurring symptoms or stent occlusions within a few years.
Finally, CMS has recently been giving attention to the evidence basis around these costly interventions. In 2016, a Medicare Evidence Development and Coverage Advisory Committee (MEDCAC) panel found limited evidence to support use of any therapy for chronic venous disease. In the current economic climate, it is our duty to conduct the needed studies to secure access to appropriate care for our patients.
What are the benefits for investigators who want to participate as clinical centers in C-TRACT?
IR investigators who participate in C-TRACT can offer their patient access to study participation, which is essentially a structured program of quality PTS care and monitoring. Participation in an NIH-sponsored randomized trial enables IRs to present themselves as highly credible, evidence-driven and balanced, which can enhance relationships with other providers and lead to more referrals for consultation.
Investigators will also gain familiarity with the rigor and process associated with NIH-sponsored, FDA-monitored clinical trials, adding to their own professional development as researchers. I think any site investigator who participated in the ATTRACT Trial would agree that being part of a large, collaborative network is motivating and educational, and the same will be true for someone who joins our C-TRACT community. There is incredible expertise and commitment in our research consortium.
If an institution or investigator is interested in participating in C-TRACT, who do they contact? Are criteria must an investigator meet to participate?
Interested investigators can contact me directly at vedanthams@mir.wustl.edu. We seek teams that deliver high-quality, multidisciplinary venous care and that specifically possess a strong ability to re-open occluded iliac veins; ability to deliver anticoagulation, compression and professional venous ulcer care; institutional ability to function in a rigorous trial with NIH and FDA oversight; and a willingness to be highly proactive in putting in place mechanisms to identify and enroll PTS patients, working with us.
How does the collaborative scope of this study compare to the ATTRACT Trial?
The two studies are similar. Both were funded by large NIH grants and both have the support of a large, diverse medical community. Like ATTRACT, the C-TRACT Steering Committee and investigator network includes experts from IR, vascular surgery, vascular medicine, cardiology, hematology, thrombosis epidemiology, economics and biostatistics. Professional society endorsements for C-TRACT include SIR Foundation, American Venous Forum, American College of Venous and Lymphatic Medicine, the North American Thrombosis Forum, the National Blood Clot Association, and the Society for Vascular Medicine. We have an incredible community of providers, scientists and others to support us.
How do the results of the ATTRACT Trial influence your expectations for, and conduct of, C-TRACT?
On the one hand, ATTRACT provided a sobering reminder that the treatment effects that are reported in preliminary experiences often exceed what is found when an intervention is subjected to rigorous, controlled testing with strong precautions against bias, by a broader group of providers. But in December 2018, we published the results of the ATTRACT Trial in its iliofemoral DVT subgroup in the journal Circulation. We found that in this subgroup, catheter-directed thrombolytic therapy did reduce the severity of PTS and improve health-related quality of life. So it is true that, in light of the overall study results, strong caution is indicated in using thrombolysis as first-line DVT therapy. But when you think about it, the ATTRACT iliofemoral subgroup analysis probably represents the strongest currently available evidence in favor of the idea that an open iliac vein may be good for patients. This is exactly what we are studying in the C-TRACT Trial, in the chronic phase of the same disease.
Tell us more about the C-TRACT referral app. What is it and how do investigators use it for C-TRACT?
With a somewhat narrow study population (moderate-to-severe PTS with iliac vein obstruction), this study will be hard to enroll with just 20–40 sites. So, it is important for us to be able to offer study participation to patients outside our investigator network. To accomplish this, we have made study referral easy by developing a smartphone app. It is is currently available for download in the Apple and Google app stores by searching “C-TRACT” or you can go to the bottom of the page at bloodclotstudy.wustl.edu/c-tract/health-provider-referral.
In the app, you answer three quick yes/no questions and provide a contact number for you or an assistant (no patient identifiers are transmitted), a message is sent to us, and we call back and connect you up with the nearest study site. The whole idea is that, in 10 seconds and without breaking stride, a provider can refer a patient to the study, and we will do the work of sorting out whether it makes sense to connect up to a study site and help to engineer that connection.
Do you have any other comments on the C-TRACT trial?
It is no small thing for the NIH to make another large investment in an IR-led venous disease trial. This likely reflects a sense that we may be onto something that can meaningfully improve patient care. Hopefully, it also reflects continued awareness of the bigger-picture potential for IR to contribute to important research that advances care.
But this depends on how well we can come together as a community to make sure the trial gets done successfully and to continue to make the NIH aware of the incredible innovative capacity of our specialty.
As investigators, we greatly appreciate the incredible support that we received for the ATTRACT Trial from many parties but especially SIR Foundation. This community support was instrumental in our success, and we have no doubt it will prove so again.
