There continues to be great optimism about the potential for interventional therapies to transform the management of venous disease, due in part to new tools (e.g., direct-acting anticoagulant drugs, intravascular ultrasound and venous stents) and new trial results. For example, in January 2020, the detailed quality of life (QOL) results of the ATTRACT trial were published, showing that patients with acute iliofemoral deep vein thrombosis (DVT) experience improved venous QOL (especially within the first 6 months) with use of pharmacomechanical catheter-directed thrombolysis.
However, there are also reasons for concern. Although we live in an era where personalization of care is desired, there is increasing recognition that venous treatments are not always targeted to “the right patient at the right time” and that long-term risks and unknowns are often neglected in patient discussions and treatment decisions. Constructive expressions of this concern within the venous endovascular community have included an increased focus on medical ethics at meetings held by venous provider organizations, development of acceptable use criteria (AUC) documents by professional societies including SIR, and successful collaborations on important research studies (e.g., PRESERVE study of IVC filters).
Notwithstanding these efforts, physicians who care for patients with chronic DVT and post-thrombotic syndrome (PTS) continue to be in a particularly difficult, “low-information” situation. When an iliac vein obstructive lesion is identified in a patient with PTS, many IRs have been trained to place stents to try to alleviate the patient’s current difficulty. However, this aggressive but short-sighted approach places the patient and their IR provider at risk since: 1) it is not known how often a patient will experience a sizable benefit and how long and to what degree it will last, because many factors beyond iliac vein status influence venous disease severity; 2) early studies suggest that iliac vein stent patencies are mediocre for patients with PTS; and 3) in the modern medicolegal and communications environment, physicians who implant permanent devices into patients shoulder major reputational risks.
The modern IR is committed to their patients and is comfortable taking on such risks when the overall risk-benefit proposition is clearly understood and shared with patients. But because there are no multicenter randomized studies of stent placement for PTS, this is simply not possible at the current time.
Fortunately, there is a solution: the NIH-sponsored Chronic Venous Thrombosis: Relief with Adjunctive Catheter-directed Therapy (C-TRACT) clinical trial.
On March 1–2, 2020, the C-TRACT Trial held its annual Investigator Meeting in Amelia Island, Florida, in conjunction with the 2020 Meeting of the American Venous Forum (AVF). At the meeting, Suresh Vedantham, MD, FSIR, C-TRACT principal investigator, and Brajesh Lal, MD, AVF president, reflected the newly announced formal partnership between C-TRACT and AVF and together highlighted the close alignment between the historical legacy of the AVF in promoting evidence-based venous practice and the goal of C-TRACT to develop randomized trial data to support iliac vein stenting for management of PTS.
At the start of the meeting, Dr. Vedantham highlighted the positive impact of the trial: the opportunity to help patients by bringing PTS care into the era of evidence-based medicine; the tremendous multidisciplinary commitment and expertise of the C-TRACT Steering Committee and investigator network; and the strong community support from organizations including SIR Foundation.
However, Dr. Vedantham was candid about the existential challenges facing the trial. Despite being active for more than a year, the study has only enrolled 55 of the needed 374 patients, far below its NIH-monitored target. He challenged attendees to explain how this slow accrual, having occurred simultaneously with thousands of venous stent placements in clinical practice, would be perceived, and how it could be reconciled with the vascular community’s stated commitment to the trial and evidence-based PTS practice. He noted that if community support enables just 1% of upcoming patients to be enrolled in C-TRACT rather than stented off-study, the trial would be completed in a year. He asked the audience how often it had seen the NIH invest $12 million in an IR-led investigator group to study PTS treatment, as they have for C-TRACT, and what message it would send to NIH and others if this once-in-a-lifetime opportunity was squandered.
In his presentation, Andrei Kindzelski, MD, NHLBI project officer, reiterated the importance of ATTRACT and C-TRACT to patients, the scientific community and the NHLBI, as outstanding examples of effective and impactful collaboration. He also emphasized the fact that financial support cannot be continued unless a major uptick in participant enrollment is seen during the upcoming months.
Attendees responded with vigor—most encouragingly, they expressed overwhelming agreement that there continues to be substantial uncertainty around the long-term benefits and risks of permanent stent implantation in PTS patients, clearly justifying randomization of patients into a high-quality trial.
Subsequent presentations included an open discussion on barriers to enrollment, a debate between IR Kush Desai, MD, FSIR, and vascular internist Suman Wasan, MD, on the best PTS treatment strategy; a dramatic re-enactment of the consent process by “patients” Ronald Winokur, MD, FSIR, and Kanti Kolli, MD, FSIR; expert guidance on best practices for medical, compressive and ulcer therapies for PTS, participant recruitment science and other study execution issues; and discussions on recently completed and ongoing/planned PTS studies.
The audience left with a clear understanding of the benefits of study participation to a potential patient:
- Close monitoring and excellent communication from a dedicated research coordinator
- Outstanding multimodality PTS care delivered using protocols endorsed by national experts and the NIH
- Free compression stockings (donated by Medi USA) and ultrasound exams
- For applicable patients, stenting in a closely monitored study environment with independent safety oversight
- For patients not randomized to endovascular therapy, excellent medical, compressive and ulcer care with the opportunity to be stented later should the study’s results demonstrate that this is the right thing to do
Dr. Vedantham closed the meeting by reiterating the value of the study for the future of venous care. In addition to providing high-quality data on optimal PTS care, success will demonstrate the effectiveness of an IR-led clinical trial network to the NIH, which can bolster the prospects of other studies and the inclusion of IRs in NIH strategic discussions and program initiatives. Participation in a study network of this kind provides IR investigators tremendous opportunities for networking with outstanding scientists and mentors and for gaining new insights into venous care and research and real-world clinical trial implementation.
Accordingly, SIR leadership entreats SIR members to support the study either by referring patients to study centers or by applying to participate as a study center. Interested members can download the C-TRACT referral app by typing “C-TRACT” into their phone’s Apple or Google-play App Store. Members can obtain more information at bloodclotstudy.wustl.edu/C-TRACT or by contacting Dr. Vedantham.
Hear more about the C-TRACT Trial from Dr. Vedantham in episode 5 of The Kinked Wire podcast. Learn more about this new IRQ podcast at sirweb.org/kinkedwire.
