C-TRACT Trial: Endovascular Therapy for Post-Thrombotic Syndrome with Dr. Susan Kahn

Post-thrombotic syndrome (PTS) affects up to half of patients following deep vein thrombosis and can significantly impair quality of life. Yet treatment options have historically been limited.

In this episode of CLOT Conversations, David Airdrie and Dr. Jameel Abdulrehman speak with Dr. Susan Kahn about the recently published C-TRACT trial in The New England Journal of Medicine.

The trial evaluated whether endovascular therapy, including iliac vein stenting, could improve outcomes for patients with moderate-to-severe post-thrombotic syndrome and iliac vein obstruction.

Dr. Kahn discusses the rationale behind the study, key findings related to symptom burden and quality of life, the increased bleeding risk observed with intervention, practical patient selection considerations, and the unanswered questions that remain regarding long-term management after venous stenting.

This episode provides clinicians with practical insights into one of the most important recent studies in the management of post-thrombotic syndrome.

Reference:

Vedantham S, Kahn SR, Marston WA, Weinberg I, Sista AK, Magnuson EA, Cohen DJ, Wasan SM, Razavi MK, Goldhaber SZ, Sanfilippo KM. Endovascular Therapy for Post-Thrombotic Syndrome—A Randomized Trial. New England Journal of Medicine. 2026 Apr 13.

https://www.nejm.org/doi/abs/10.1056/NEJMoa2519001

Transcript

CLOT Conversations – C-TRACT Trial

Welcome back to CLOT Conversations, the podcast where we explore the latest research and clinical insights in thrombosis.

I'm David Airdrie, executive director of Thrombosis Canada, and I'm joined by my co-host, Dr. Jameel Abdulrehman from Toronto General Hospital. Dr. Othman is away this week.

Today we're discussing an important and highly anticipated study focused on post-thrombotic syndrome, or PTS, a chronic and often debilitating complication following deep vein thrombosis.

We'll be reviewing the recently published C-TRACT study in the, from the New England Journal of Medicine, which evaluated whether endovascular therapy with iliac vein stenting can improve its symptoms and quality of life in patients with moderate or severe post-thrombotic syndrome and iliac vein obstruction.

We're very pleased to welcome one of the study authors, Dr. Susan Kahn.

Thanks for having me.

Dr Susan Kahn is a clinical epidemiologist and internist based at the Jewish General Hospital in Montreal, where she is a founder and director of the Center of Excellence in Thrombosis and Anticoagulant Care.

She's a professor of medicine at McGill University and the founder of the McGill Royal College AFC in Adult Thrombosis Medicine. Dr. Susan Kahn co-founded and co-directed the CanVECTOR Network from 2015 to 2025 and is internationally recognized for her work in venous thromboembolism, particularly research focused on the prevention and management of post-thrombotic syndrome. She has published more than 360 papers in thrombosis research, and in 2026 received the International Society on Thrombosis and Hemostasis Esteemed Career Award.

Dr Susan Kahn, thank you very much for joining us today.

Pleasure.

Susan, for listeners who may be less familiar with post-thrombotic syndrome, can you start by explaining what PTS is, how commonly it occurs after DVT, and why it was important to conduct the C-TRACT trial? Sure.

The post-thrombotic syndrome, as you mentioned, is a chronic complication after deep vein thrombosis. Indeed, it's the most frequent complication of deep vein thrombosis, and occurs in upwards of 20 to 50% of patients after an acute DVT.

Certain DVT patients are at higher risk than others, and that's relevant to our study, particularly patients who have a more extensive type of deep vein thrombosis. They tend to be at higher risk of developing post-thrombotic syndrome.  And in terms of what it is, it represents a kind of constellation of symptoms and signs that may differ from patient to patient.

Common themes are leg heaviness and pain that's worse at the end of the day and somewhat relieved by resting the leg. There can be swelling of the leg, a visible discoloration, development of, what we call secondary varicose veins, within the leg, and in more severe cases, venous ulcers or skin breakdown can actually occur.

And the reason this condition, post-thrombotic syndrome, is so important is that it's been shown to really affect the quality of life of those affected. Some patients have trouble working because they can't sit or stand for prolonged lengths of time. In general, it can be quite a burdensome, condition and as mentioned earlier, it's a very frequent condition.

So that was one of the reasons why we decided to conduct this trial.

Great.

And you conducted a multicenter open label assessor blinded randomized control trial comparing standard PTS care alone with endovascular therapy plus enhanced antithrombotic therapy and standard care. Could you walk us through the study design and the treatment strategies used in each arm? Sure.

I meant to mention in my last response as well that one of the reasons for conducting a trial where we're looking at an actual intervention to treat post-thrombotic syndrome is because up until now there really has not been any effective treatment using more conservative type of measures, which I'll discuss in a moment.

For this trial, we enrolled patients who had moderate to severe post-thrombotic syndrome. So we weren't focused on those with the mild condition, but those with moderate or severe who, for whom conservative approaches just don't work.

And they were randomized to either have what we call best conservative therapy where, for example, they were using compression stockings on a regular basis taking very good care of their legs and other types of sort of conservative measures.

Alternatively, they might have been randomized to receive this interventional approach which is delivered by an interventional radiologist and involves the deployment of a stent into an obstructed, a chronically obstructed vein. Sometimes veins are dilated with little balloons. The operator, or the interventional radiologist, decides what's most appropriate for each individual patient.

In addition to that intervention, they also received sort of best conservative therapy.

So once again, patients with moderate or severe post-thrombotic syndrome were randomized to one of these two interventions, either a more conservative approach or receiving this interventional radiology delivered intervention to open up the vein, clear out the vein, plus the conservative management that all the patients in the other arm got as well.

Could you tell us a bit more about the enhanced antithrombotic therapy that was used in the intervention arm? 

So because the intervention itself involves, it's invasive, it involves going into the veins, putting in a stent, kind of trying to open up a vein, with the potential for trauma because you're going into a vein, it was really important to make sure that none of these patients, later on sort of occluded the vein because of those traumas.

So, patients were recommended to remain on antithrombotic therapy as well as antiplatelet therapy for a period of six months after the intervention. And the fact is we don't really have any standard guidelines as to how to manage patients after these venous interventions. For example, if a stent is put in, we don't know if they should just be on antiplatelets or antithrombotics alone or antithrombotics plus antiplatelets.

That's sort of, in a way, a topic for a different trial.

But in this trial, to sort of maintain the integrity of the intervention, we wanted to make sure that patients were well anticoagulated, for a period of six months.

So, yes, that was sort of part of the intervention itself, was to remain on these medications for a six-month period, and after that, the individual physician managing the patient could decide what to do with their anticoagulants and/or anti-platelet drug. Six months, you found the endovascular therapy group had a lower severity of post-thrombotic syndrome compared with standard care alone, with an adjusted difference in the VCSS score of minus two points.

So what does this mean, and how do we put this score into clinical context? Okay.

So yes, the primary endpoint of the trial is the Venous Clinical Severity Score, and that's a measure that's perhaps a bit less known to us medical thrombosis docs who tend to use the Villa Alta scale, although that was measured too in this trial.

But VCSS is a measure that, traditionally, has been used very often by vascular surgeons and also interventional radiologists as a way of measuring the severity of chronic venous disease.

And it basically taps into a number of clinical signs.

I think there's only one symptom question on, on the scale, and also asks whether the patient is regularly wearing compression stockings, which is kind of a surrogate marker of bad post-thrombotic syndrome.

So a decision had been made at the onset to use VCSS as a primary outcome.

And indeed, it was powered to find a difference in VCSS between groups and at the six-month follow-up, which was the follow-up period at which the primary outcome was assessed, indeed, there was a two-point lower on average VCSS score in those who had received the endovascular therapy compared to the control arm, and this was a statistically significant difference and also considered to be a clinically significant difference because two points kind of represents midway between the four points that would be needed to jump a severity class from mild to moderate or moderate to severe.

So it is also a clinically relevant difference.

Okay, great.

And you also looked at quality of life outcomes.

Can you tell us what you found there? Sure.

So in terms of quality of life outcomes, and, and just want to make the point that when you're dealing with a chronic condition like post-thrombotic syndrome, you would be really mistaken or remiss not to measure quality of life because of the fact that patients are suffering on a day-to-day basis with their quality of life being affected.

So the measures that were chosen as endpoints for this trial are the VEINS-QOL, which is a venous disease-specific, well-validated, quality of life measure.

And then we also use the SF-36, which is a more generic physical quality of life measure. In both cases, those in the endovascular therapy group had statistically significant improvements in the quality of life measures, and the differences, between the groups, endovascular versus no endovascular, were substantial.

So for example, for VEINS-QOL,  where let's say a four to five-point difference between groups would be considered to be clinically relevant, in this case, there was close to a fifteen-point difference between groups in favor of endovascular therapy arm.

Along the same lines for SF-36, there was a six-point difference between groups where for that measure, about a three-point difference is considered clinically relevant.

The, the quality of life results were certainly aligned with the results for the primary outcome, the VCSS.

Okay.

And you also looked at bleeding outcomes as well. Can you tell us about what you found there? Yes, of course.

So any treatment that involves an intervention that involves puncturing the skin or puncturing a vein, of course  It's going to be very important,  to look at bleeding as a part, as a possible adverse outcome. Bleeding was indeed more frequent in those who received endovascular therapy. The fact is that bleeding was assessed, throughout the six-month follow-up period, but indeed it mostly happened during those initial 30 days. Bleeding was assessed throughout the six-month follow-up period, and just to remember that this was the period where patients were receiving both antithrombotic and antiplatelet therapy and indeed,  most of the bleeds occurred sort of later on in the six-month follow-up period.

So I think we can consider that it's more likely to be attributable to the co-intervention, so to speak, with the antithrombotic and antiplatelet therapy than from the actual interventional radiology procedure itself.

But with that proviso it does have to be considered when you're thinking about whether or not a patient should be selected for these types of approaches, and we can maybe talk about that a little bit later.

 But you have to consider the fact that there is a higher risk of bleeding in patients.

Interesting.

So how did the results of the C-TRACT trial compare with prior studies looking at endovascular treatments to treat post-thrombotic syndrome? So this is in fact the first  multicenter, rigorously designed, trial of endovascular therapy, compared to the control of,  no in-endovascular therapy and standard post-thrombotic syndrome care to improve the post-thrombotic syndrome.

There have been a couple of,  previous single center trials, small trials that looked at a similar intervention in similar types of patients, and results were similar in the sense that the intervention did show, a reduction in severity of post-thrombotic syndrome, which was measured in various ways in these two prior smaller trials.

And aside from those two prior single center smaller trials, there have been a few, single center kind of registry studies with sort of pre-post measures. Looking at how the patient was doing before they got the intervention, and then seeing how they do after the intervention without there being an actual, control group.

So, this trial, the C-TRACT trial, represents a new, you know, large multicenter study that provides information that is kind of supported by the previous smaller trials that were done.

Okay.

So what are some of the key limitations of the trial that clinicians should keep in mind when interpreting the results and applying them in practice? Right.

So maybe before the limitations, I could talk for a minute about the strengths, because there were a lot of strengths to this study.

Let's do that.

I think the fact that all of the outcome measures for efficacy were moving in similar directions, although each of the efficacy measures tapped into slightly different aspects of post-thrombotic syndrome, sort of strengthens the causal inference in terms of an effect of endovascular therapy, to improve the post-thrombotic syndrome.

There was also blinded outcome adjudication, independent safety oversight with a data safety monitoring board, and there was, as we often do, a centralized concealed randomization. So all of these aspects reduces the risk of systematic bias.

And I also would like to point out that unlike in some of our Canadian trials, quite a diverse population was enrolled. So there were 47% women, 24% Black participants, 12% Hispanic or Latino, and I think that this also tends to enhance the external, validity of the trial.

 In terms of limitations, the fact that there was an increase of bleeding in the endovascular therapy arm, even though it might have been explained by the co-interventions, namely the antithrombotic and antiplatelet therapy, still it means that one has to be careful about which patients potentially to select for this intervention. 

And the trial doesn't really give us any information on whether the six months of antithrombotic and antiplatelet therapy was, for example, excessive. Could we have gotten away with a reduced, time course of those drugs or less intense use of those drugs? We simply don't know, and as I said, it wasn't assessed in this trial itself.

Other potential limitations are that because the intervention which was chosen by the individual interventional radiology practitioner involved a variety of components, so it could've been a stent, could've been venoplasties, balloon venoplasties. It's very hard to tease out, which of the individual components led to the outcome.

But this, in fact, reflects real world, where if you do send a patient along to IR for consideration of a procedure like this, the IR practitioner has to use their expertise to decide which is the best,  intervention or c- combination of interventions,  to treat this particular patient's anatomy and symptomatology.

Um, so I think those are sort of the most, um, important limitations.

And maybe if I could add one more, it's that this trial, so far, has only reported on six-month outcomes. My task over the next little while is going to be to write up a paper that actually looks at outcomes out to two years. So we're going to look at the durability of the effect, is quality of life still better, out at two years, are the clinical measures still better? We don't know. That's to be determined once we have those data analyzed.

Okay.

Great.

So from a practical perspective, who is the patient with post-thrombotic syndrome that should be referred for consideration of endovascular therapy? 

So in terms of which patients you might consider referring, for endovascular therapy, I think we have to start off by looking at the inclusion criteria of the trial. Once again, we included  patients who had moderate or severe post-thrombotic syndrome and who were also shown to have iliac vein obstruction, because these tend to be the patients with the most disabling type of post-thrombotic syndrome. Patients who had had a very recent DVT were excluded, so I think that would be a factor to consider.

Let's say they were at particular high risk of bleeding. Let's say you applied a bleeding score, or there was, you know, fears or concerns about bleeding. You might hesitate about referring a patient for this procedure. And then the other thing, of course, is that operator ability or skill is an important consideration. 

So you would want to make sure that the patient be referred to a center that has a lot of expertise in performing these kinds of procedures because they are not done every day. And, often you need an IR specialist who has particular training in venous procedures, you know, not just a general sort of IR specialist.

I think that all of those things would have to be considered in terms of whether or not to think about suggesting endovascular therapy for a patient with post-thrombotic syndrome.

Okay.

So you mentioned earlier that after the stenting we don't really have good guidelines, we don't really have good data for how long to do antithrombotic, anticoagulant, antiplatelet after. 

In your personal expertise could you share with us what your approach is after stenting? Sure.

So we have to keep in mind that a stent is a foreign body in a vein.

And, you know, once a patient has developed post-thrombotic syndrome after a deep vein thrombosis, and if it's bad enough that they end up having a stent inserted the absolute last thing you would want for your patient is to have a recurrent episode of deep vein thrombosis in the future.

So, in my personal practice I tend to use severe post-thrombotic syndrome on its own.

And it would be even more so if there was a stent in situ as a reason to continue long-term anticoagulation in these patients to prevent an episode of recurrent DVT in the same leg, which could really aggravate,  post-thrombotic syndrome, and it could even negate the effect of having the stent in place. If a patient gets a big clot and it clots all the way up to the stent, that's a very bad thing for the patient.

So, for me, to prevent venous thrombosis, I would tend to use an anticoagulant, not necessarily couple it with an antiplatelet drug, because I don't know, we don't really have good trial data to tell us that that's, you know, effective but also safe in terms of bleeding. That's what I would do, in my current practice now.

The fact is, given that the C-TRACT trial that we're talking about did have patients on both an antithrombotic and an antiplatelet drug for six months after the procedure, maybe I would be a little more open-minded about using that combination as well in my patients moving forward.

But I would just have to make sure that I feel comfortable about their bleeding risk, being on the dual therapy before making an individualized decision, for my patient.

That's great.

Is there anything that we haven't discussed that you'd like to add, particularly regarding the future direction of research or how you hope the study will influence clinical practice? Sure.

So I think that, many thrombosis physicians feel like, there's nothing we can do for our post-thrombotic syndrome patients, that it's too bad that they ended up with this chronic condition, and the horse has left the barn.

They've had damage to their veins, and they're just going to have to live with it.

I think that this trial provides a lot of hope for patients who are suffering with post-thrombotic syndrome. If the right patients are selected for this intervention, they could benefit from it to a point where, as we saw, the quality of life can be markedly, improved.

In general, I would say that more research is needed in this whole clinical space.

I mean, understanding more why patients get post-thrombotic syndrome.

Why is it that the ATTRACT trial that looked at, using catheter-directed thrombolysis at the time of acute DVT, didn't find a measurable impact on post-thrombotic syndrome? Even though some of the secondary outcomes were statistically significantly different, but overall it was not a positive trial.

So I think more research is needed to better understand why it happens, what can we do at the time of acute DVT to maybe mitigate or offset the risk of getting post-thrombotic syndrome.

And there are a few great Canadian trials, at present that are looking at using different drugs like statins, colchicine, and others to maybe try and reduce that risk. And then once a patient has post-thrombotic syndrome we need a lot more research into what we can do,  to help them.

And, I think the C-TRACT trial is kind of a great, step in helping to solve some of those issues for our patients who are really suffering on a day-to-day basis with this condition.

Dr. Kahn, thank you for joining us and for sharing your insights into this important study.

Thank you so much.

Bye-bye.

And, for our listeners, we'll include a link to the full publication in the show notes.

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