Dr. Frank R. Arko Describes the FDA Early Feasibility Trial for Stent Graft

Q: Could you tell me about the FDA’s early feasibility pilot program that you are involved with?

A: This is a great step forward for getting devices looked at in a first-in-man approach in the United States. In the last several years most of the first-in-man have had to be done outside the United States. The Food and Drug Administration has looked at this and started to try to move some of this early innovation and assessment of technology in first-in-man trials to the United States. The Valiant Mona LSA system is one of the grafts that is going to be looked at in this regard.

Q: How was the Valiant Mona LSA system selected?

A: The Valiant Mona LSA system is a stent graft that has a branch on it that allows for percutaneous revascularization of the left clavian artery. Many of these patients with an aneurysm in which you’d have to put in a Valiant or another stent graft require either surgical bypass of the left clavian artery or just complete coverage of the left clavian artery. It’s very controversial as to whether that left clavian artery needs to be revascularized or whether it can just be covered. But this will allow us a system to be studied in the United States to see if this is a feasible and safe way of doing this procedure. 

Q: Were there certain criteria for selection of devices and locations?

A: This is a new thing for the FDA, and it’s important. I have been involved for quite some time from the early prototype to this first-in-man study, but I’m not an expert in what’s involved for the FDA to give you approval for this study.

Q: Do you know when the process will be completed?

A:  When it will be completed will be difficult to tell, because you first have to determine when it’s going to get started. The plan for it to start is actually basically getting things through the IRB, probably near the end of this year – maybe around the October/November timeframe – and then it will take some time for that to be approved through the institutional review process, and then there will be contracts to be signed.

The hope is that the first-in-man trial will actually begin very early in 2013, so maybe in the month of February. We actually need very few patients for the first-in-man trial, somewhere between 7 to 9 patients. How long it takes to enroll that number will determine the overall length of the trial so I hope that maybe within 6 months or so the trial will be completed. Then there would be a need for follow-up.

Q: Are you selecting the patients currently?

A:  I am not currently selecting those 7 to 9 patients because most of the patients that get referred to me would typically require therapy earlier than 6 to 8 months down the road, so it would be a little bit long for them to wait. Once the study starts getting through the IRB process and contracts are signed and approved then I would really start looking for patients to enroll.

Q: What do you hope to find out about the Mona Lisa system?

A:  That is a great question and the answer would be that, first, we’re really looking to see if it’s safe to use the device in the treatment of these patients with revascularization of the left subclavian, and then we want to be sure it’s effective in treating these patients. We will look for a much shorter neck, which is the proximal area where you’re trying to get a seal in those patients selected for the Mona LSA system.

What we would like to determine in this small series of patients is that it’s safe to implant the device and that it’s effective in achieving a seal and preventing any rupture of those aneurysms. Those are the two main goals. The third goal would be that when you put in a branch and it goes to an end organ, in this case it’s the posterior circulation of the brain and the other one is the arm, you want to be sure those end organs still have good perfusion, so we want to be sure it’s safe, that it is effective in preventing type 1 leak and/or rupture of the aneurysm, and that the branch remains patent.

Q: Pending approval when you evaluate those main goals, when would commercial availability probably occur?

A:  It would take some time after that, because this is only a feasibility trial with a small number of patients to be sure that it’s safe. If any changes need to be made to the graft, they would be made, and then it would require a much larger clinical trial involving many more centers and a significant increase in the number of patients over the single-digit numbers we’re using in the feasibility trial.
This feasibility trial is a first step when you’re really trying out any sort of new device and you’re going to get rid of a surgical procedure, and when there are a lot of things that are unknown and it takes time. But, you can learn a lot in the first 10 or so cases and based on those 10 cases make any changes that need to be made. Then those are brought to a larger clinical trial to be evaluated.

Q: Are there any limitations that you are concerned about for this or any future studies?

A:  I think it’s such a huge step forward compared to what we’re currently doing and the implantation of the device is so much simpler, certainly my hope, being optimistic, would be that we wouldn’t have any limitations and no significant changes would need to be made. Are there limitations? I think that there may be limitations based on maybe the degree of angulation of the proximal aorta.

I’ve been involved in the process of the design of this device and implantation, and all cases to date have been in animals. The anatomy in humans will certainly be much different than that in animals and we may certainly find limitations that have not been accounted for in humans that have been in the animal model. So I think there’s a potential to find limitations that may require us to make some changes, but I think overall the device is very well designed and I’m not sure that there will be much in the way of limitations.

Q: Is there anything else you’d like to share?

A:  There has been a lot of research and development for this design. We’ve investigated this device from a computational analysis standpoint, used animal models and flow models, and examined movement of the thoracic aorta involving both cardiac and respiratory movement. We believe this will limit any surprises once this is implanted in humans.

___________________________________________

Dr. Frank R. Arko is a vascular surgeon at Sanger Heart and Vascular Institute at Carolinas Medical Center in Charlotte, N.C. Dr. Arko reports consultancy to Medtronic.