Medtronic plc reported promising results from a feasibility study of its In.Pact 0.014 drug-coated balloon (DCB) in critical limb ischemia (ICL) patients with chronic total occlusion (CTO) in the infrapopliteal arteries. The below-the-knee (BTK) device could offer an effective DCB option for patients with this challenging vascular condition.

The prospective, multicenter, randomized In.Pact BTK study evaluated the safety and effectiveness of the In.Pact 0.014 DCB, a 3.5 μg/mm2 dose paclitaxel-coated balloon, compared with percutaneous transluminal angioplasty (PTA) for the treatment of infrapopliteal artery CTOs. A total of 20 patients were enrolled across nine European sites.

The effectiveness outcome measure was nine-month lumen loss – specifically subsegremental late lumen loss, or lumen loss along the entirety of the lesion – and classic late lumen loss at the narrowest segment of the artery. The safety endpoints were a composite of freedom from device- and procedure-related mortality within 30 days, freedom from major target limb amputation within nine months and freedom from clinically driven target limb revascularization CD-TLR) within nine months post-index procedure.

Lower late lumen loss

At nine months, the DCB group had less subsegremental late lumen loss than the PTA controls (0.59mm +/- 0.94mm versus 1.26 mm +/- 0.81mm, p+0.017), for a 53% lower late lumen loss with In.Pact 0.014.

When assessed using the classic late lumen loss approach, patients in the treatment group experienced 32% lower late lumen loss than those in the PTA group (0.89mm +/- 0.77mm versus 1.31mm +/- 0.72 mm).

On safety, DCB and PTA groups showed no statistical difference in nine-month composite safety index. The DCB arm recorded no device- and -procedure-related deaths at 30 days vs. 3.7% of controls. There were no target limb major amputations in either group within the study period, and both groups reported 8.7% CD-TLR within the nine months.

“The design of this feasibility study is incredibly thorough and required rigorous procedural duplex ultrasound and angiographic protocols to more accurately evaluate these complex lesions,” said Antonio Micari, a cardiologist at the University of Messina in Italy. “Despite enrolling subjects with challenging lesions commonly seen in BTK disease, including those with CTOs, long lesions and severe calcification, the results of the study are promising.”

The results were presented at a late-breaking clinical trials session at the virtual 2020 Transcatheter Cardiovascular Therapeutics conference.

Large unmet need

An estimated 2 million people in the U.S. suffer from CLI, a number that is likely to rise in coming years given trends in key risk factors such as age, diabetes and smoking.

“Historically, there has not been a DCB technology that has demonstrated effectiveness in this vessel bed in a randomized clinical trial,” Mark Pacyna, vice president and general manager of the Peripheral Vascular Business, part of Medtronic’s Cardiac and Vascular Group, told BioWorld. “While this trial is relatively small, the data from this study suggest that In.Pact 0.014 may offer a clinical benefit in patients with CLI. Furthermore, we feel this feasibility study offers important insights that will enable future trials based on this same formulation that has also demonstrated effectiveness in the market-leading In.Pact Admiral DCB and the In.Pact AV DCB.”

The In.Pact 0.014 DCB is currently being evaluated in Europe and has not been assessed in the U.S. Medtronic declined to provide a timeline for entering either market.

The company’s In.Pact DEEP study evaluated the earlier generation In.Pact Amphirion DCB, and while the trial did not meet its effectiveness endpoint, leading Medtronic to remove the device from the market in 2013, five years of data from that study have deepened understanding of BTK disease.

“As a result of our learnings from the In.Pact DEEP and this latest study, we have a more complete understanding of this challenging vessel bed, as well as deep expertise in BTK clinical trial and product design,” Pacyna said. “Medtronic has a long-standing commitment to the BTK disease state and, in the future, intends to pursue In.Pact 0.014 DCB BTK studies and commercialization globally.”

In August, Medtronic touted primary endpoint results from the In.Pact AV Access trial, which showed the paclitaxel-coated balloon limited the number of reinterventions needed to maintain blood flow in patients with end-stage renal disease who have arteriovenous (AV) fistulae. The result was fewer interruptions in patients’ dialysis therapy.

The In.Pact family leverages technology from Medtronic’s In.Pact Admiral DCB, which first won U.S. FDA approval in 2015 for the treatment of above-the-knee superficial femoral artery lesions.

Competitive field

Other companies are working to alleviate peripheral artery disease. In April, Intact Vascular Inc. won FDA approval of its Tack endovascular system (4F), the first peripheral vascular implant to repair BTK post-angioplasty dissections.

In June 2019, Micro Medical Solutions won the FDA’s nod for a clinical trial of its Microstent system to reduce BTK amputations in patients with CLI due to PAD. And in January, Ra Medical Systems Inc. announced a greenlight for an IDE study of its Dabra excimer system as an atherectomy device to treat peripheral vascular stenosis. The minimally invasive system, which clears clogged blood vessels using photochemical ablation, received 510(k) clearance in 2017 for the treatment of occlusive peripheral vascular disease.

Also in the game is Pq Bypass Inc., which got the FDA’s OK for a pivotal trial of its Torus stent graft in the treatment of PAD in the superficial femoral artery. The TORUS-2 study is the company’s second IDE approval in less than two years and the first pivotal IDE for an SFA stent graft since W.L. Gore & Associates’ Viabahn device, which first secured FDA approval in 2005.

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