At the 2014 VEITHsymposium, Peter Schneider, MD, shared results from the European and US arms of the IN.PACT SFA trial, a multicenter randomized trial that evaluated safety and efficacy of the In.Pact Admiral drug-eluting balloon compared to plain balloon angioplasty. Vascular Disease Management spoke with Dr. Schneider about the 1-year results. 

Q: Could you start by describing for us the design of SFA I and II?

A: The In.Pact randomized controlled trial of the In.Pact Admiral drug–coated balloon vs PTA was made up of 2 phases, called SFA I and SFA II. SFA I was a multicenter trial in Europe. A number of patients that were entered into that trial were then evaluated for safety of the device and that was used to apply for investigational device exemption from the FDA, which helped us plan and initiate the SFA II trial. One of the tricky things, if you will, about this whole trial is that you really want the patients in SFA I and SFA II to be poolable, that is to be similar enough groups so that at the end of the study, we have a clear-cut answer as to what we’re investigating. And there were a couple of lessons learned from SFA I that helped inform SFA II. For example, in SFA I, both clinical and angiographic entry criteria for the patients were nearly identical, with one slight difference, which was that with SFA I, predilation with a smaller balloon prior to the use of a drug-coated balloon was suggested but not mandatory. In the SFA II trial, this became mandatory and something that, of course, the FDA was highly interested in and wanted to pursue as a uniformly performed step. That’s something we knew at that point that we didn’t know in the beginning of SFA I. So there were some slight differences like that but at the end of the day, the FDA, I believe, will agree that the 2 studies are poolable and when one looks at the data, it’s otherwise difficult to find any significant differences between the SFA I and the SFA II trials. 

Q: Could you go into detail about the objectives and the results from both I and II?

A: The objectives of SFA I and II are identical, that is safety and efficacy. The safety endpoint was a predefined endpoint that had to do with avoidance of amputation, avoidance of occlusions, and avoidance of any repeat interventions, and then with respect to efficacy, the primary patency figure was the most important and the efficacy was really a combination of primary patency plus avoidance of a repeat revascularization.

Q: And how were you involved in the study?

A: I personally was involved in helping to plan the trial from early on, starting in 2010. We didn’t enroll patients in the SFA II trial in the United States until much later, so of course this was a very anticipated activity and we were very excited to finally roll this out into the United States after years of discussing it. SFA 1 had gone very well, but ultimately, once we began to enroll the SFA 2 trial, the investigators were so enthusiastic about using the device and patient recruitment that we actually enrolled it very quickly. So our big anticipated opportunity to use drug-coated balloons was actually very short in terms of the actual time frame. I think we enrolled SFA 2 in just about 8 months and of course you have kind of a protracted period of follow-up. You want to make sure the safety and efficacy is adequate before submitting that data to the FDA, which of course has been done now. 

Q: How much follow-up will there be?

A: Well, at this time we have set 1-year follow-up and that’s been presented. I presented it here earlier this week at the VEITH meeting. There is a commitment from the study sponsor to go up to 5 years, which we believe is extremely important with the introduction of any new technology to look for the possibility of long-term problems on one hand, but also because as the field of the non-coronary endovascular world becomes more sophisticated and we develop longer lasting treatments, the 1-year follow-up time frame, is not sufficient. A 5-year follow-up will be extremely helpful. It will help the physicians in making decisions about future therapy options as well. 

Q: How about some remarkable points from the 12-month data?

A: Some issues around the 12-month data that we were very excited to see and gratified about were that there’s a dramatic difference in patency between drug-coated balloon and plain balloon. Of course, plain balloon is having its 50-year anniversary this year. It’s hard to believe that it’s been a workhorse for 5 decades in a field that we consider to be still a relatively young field. But I think that the dramatic improvement in results, based on the use of the drug-coated balloon in comparison has a very high chance of leading to a future scenario where drug-coated balloons are one of the first choices that physicians make and that the plain balloon is not used as readily. 

Also, when we looked at how men did and how women did, there was a significant advantage for both genders with the use of drug-coated balloon as compared to PTA and when we looked at how diabetics did, compared to nondiabetics, we found the same dramatic improvement with drug-coated balloons as compared to PTA. Something on the order, in each of those groups that I mentioned, of a 20% to 30% absolute improvement in patency rate at 1 year when comparing drug-coated balloons to plain balloons.

Q: What’s most important about SFA I and II for vascular clinicians to know?

A: There are a couple of things to note. One is that I think that the current drug-coated balloon trials that are just recently concluded will form a paradigm for how these trials might be done in the future. The ability to pool patients over a wide geographic area is extremely helpful to our trial enrollment and also in looking at how broadly applicable the device is. Also, in the SFA trial, the controls were extraordinary in the sense that there were independent core-labs for duplex and for angiography, an independent data-safety monitoring board, and an independent clinical events committee that adjudicated all complications and re-interventions. Part of this added safety is due to the fact that the drug-coated balloon is a new technology for our patients — at least in the periphery, but also this is probably a preview of coming attractions for how many future trials will be conducted to try to remove as much bias as we possibly can from the results by doing as much blinding and as much independent adjudication as possible. 

Peter Schneider, MD, is a vascular surgeon with the Hawaii Permanente Medical Group for which he serves as chief of the division of vascular therapy and Director of New Ventures. Dr. Schneider reports that he is a member of the scientific advisory board for Medtronic.