Medtronic plc has had a couple of failed trials in below-the-knee peripheral arterial disease (PAD) with its drug-coated balloon (DCB) technology. Now, the Dublin, Ireland-based med-tech giant is giving it another shot with a small, European study using improved technology and clinical trial design.

The results, expected in 2020, could offer initial evidence that DCBs can provide enough long-lasting vessel patency to improve wound healing in tough-to-treat patients. Competitor C.R. Bard Inc. is the only company with an ongoing IDE trial for a DCB in arteries below the knee.

"We have a lot of history with below-the-knee trials, with two failed trials already. A competitor is also taking another run at it," noted Mark Pacyna, vice president and general manager of the peripheral business in Medtronic's Aortic & Peripheral Vascular division, in an interview with Medical Device Daily.

Medtronic said it's incorporating what it has learned, particularly from the prior IN.PACT DEEP trial as well as from its approved DCBs that have been used in hundreds of thousands of patients with other conditions, to design a better device and an improved clinical approach.

Below-the-knee PAD can lead to critical limb ischemia (CLI), which is associated with a risk of non-healing wound ulcers and amputation.

Current approaches, such as non-drug-coated balloon angioplasty, atherectomy and stent placement, aren't typically sufficient to establish a durable enough treatment to provide enough time with improved blood flow to ensure wound healing.

"With critical limb ischemia, you want to get flow down to those wounds. It does take some time to have that vessel patent, at least three to six months until you have to have good flow there to address that wound," said Pacyna.

"Many of the technologies today will open it up, but how long can you expect that vessel to be patent and to allow the patient to restart activities in life that are important to them?" he queried, adding "Patency below the knee is one of those areas that hasn't been well studied yet."

PAD is estimated to affect 3 percent of people from 40 to 48 years old, with about 20 percent of people over 70 being afflicted. It's often accompanied by CLI with limb pain that can lead to limb loss once blood flow is compromised long enough.

LEARNING FROM HISTORY

The newly started European IN.PACT BTK study will test the Medtronic IN.PACT 0.014 paclitaxel-coated percutaneous transluminal angioplasty (PTA) balloon catheter in below-the-knee PAD. The prospective randomized 60-patient trial will be at four sites; half of patients will receive standard PTA treatment.

The primary endpoint of the trial is late lumen loss at nine months, which is expected to offer an angiographic measure of the drug-coating's effectiveness. The study includes a wound care protocol to better ensure standardization of that front. The trial is expected to have a nine-month enrollment, followed by nine months of follow-up with data in 2020.

"Looking at the DEEP trial, here's what we're doing differently. We are being much more specific around requirements for wound care protocols. We think that's critical for the outcomes and are having that well controlled in this trial," said Pacyna.

He continued, "Vessel sizing matters, lumen gain matters and we have paid a lot of attention to vessel preparation. We want to get appropriate vessel sizing and lumen gain through the trial protocol. All three of those, we believe, will impact the efficacy."

In addition, the device itself is distinct from prior iterations, according to Medtronic. It is made with a new balloon material and coated using a more rigorous process while the balloon is inflated, rather than when it was already folded as was done previously.

"The coating and the platform will make a difference," concluded Pacyna.

BARD PIVOTAL TRIAL IN BTK

Competitor Bard started its pivotal DCB trial in below-the-knee PAD in 2013. It's expected to enroll up to 1,000 patients; primary outcome data collection was slated to complete last month, with a September 2019 date to complete the study.

The Bard BTK trial is specifically for patients with stenosis or occlusion of native arteries with a cumulative lesion length up to 320 mm with reference vessel diameters of 2 mm to 4 mm. The Medtronic BTK includes the same vessel diameter specifications.

The Bard primary safety endpoint is freedom from major adverse limb event or postoperative death at 30 days and the primary efficacy end point is a composite of limb salvage and primary patency at six months. Last fall, the FDA agreed to modify the primary endpoint to a six-month time point for the Lutonix 014 Drug Coated Balloon PTA Catheter.

In the Bard trial, which had enrolled 340 patients last fall, more than two-thirds of patients enrolled at that time were diabetic with 95 percent of all patients having CLI.

Summed up Antonio Micari, of Maria Cecilia Hospital in Cotignola, Italy, who performed the first procedure in the new Medtronic trial, "Given the chronic nature and comorbidities of this disease, there is a critical need for treatment options that are safe and durable."