Medtronic plc is highlighting the publication of primary endpoint results from the In.Pact AV Access trial in the New England Journal of Medicine (NEJM).

Of note, the study found that the Dublin-based company’s paclitaxel-coated balloon limits the number of reinterventions needed to maintain blood flow in patients with end-stage renal disease (ESRD) who have arteriovenous (AV) fistulae. As a result, patients experienced fewer interruptions to their dialysis therapy.

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

Patients require an AV fistulae to receive continuous dialysis, and maintaining access to these sites is essential. Vessels that feed the access site can narrow over time, and patients often undergo multiple maintenance procedures per year to restore access site function.

In fact, these patients typically undergo maintenance procedures two to three times a year. The actual procedure, which often is done in an outpatient setting, takes about an hour, and clinicians have been using plain balloons for many years.

“We have to remember that these patients who have [ESRD] are really sick,” Mark Pacyna, vice president and general manager peripheral vascular at Medtronic, told BioWorld. He added that there are more than two million people globally who are actively on dialysis – and roughly 700,000 in the U.S. – who must go to the clinic three days a week.

Study overview

“What we were excited about when we got FDA approval last fall, and what we’re thrilled about frankly today, is the recognition that In.Pact Admiral and In.Pact AV here is really a unique tool that is the first DCB to hit both their safety and efficacy endpoints in this really challenging patient population.”

The randomized, controlled study enrolled 330 subjects in the U.S., Japan and New Zealand. Through six months, the rate of target lesion primary patency was substantially higher in those in the In.Pact AV DCB group vs. those in the percutaneous transluminal angioplasty (PTA) control group (82.2% vs. 59.5% (p<0.001)).

In addition, patients treated with In.Pact AV DCB required 56% fewer reinterventions to maintain lesion patency compared with those treated with standard PTA through six months. For its primary safety endpoint, the In.Pact AV DCB group showed noninferiority vs. the PTA control group in the rate of severe adverse events involving the AV access circuit within 30 days. Through 12 months, the mortality rate was comparable between the In.Pact AV DCB group and the PTA control group (9.4% vs. 9.6%).

COVID-19 impact

In May, during Medtronic’s fourth-quarter earnings call, CEO Geoff Martha said that there had been an impact on the launch of the AV fistula indication for the DCB in the wake of COVID-19.

However, with the pandemic, stakeholders pushed the health care system to deem these as emergency, not elective, procedures. Pacyna said the company has seen a return to normal levels for fistula maintenance procedures over the past couple of months. He stressed that reducing the number of maintenance procedures for patients also is important during this time. “Every touchpoint with the health care system today is riskier than it was yesterday,” with the pandemic.

Already, the feedback has been positive, mirroring the results seen in the published study, Pacyna confirmed. For his part, Robert Lookstein, with Mount Sinai Radiology and NEJM lead study author, told BioWorld that treatment with In.Pact AV has had an impact both on the target lesion and on the function of the entire AV shunt itself.

“It’s without question, a very simple, low-cost intervention that improves their outcomes for any dialysis maintenance procedure,” Further, it can help them avoid historically unnecessary procedures in a doctor’s office, ambulatory surgery center or hospital outpatient facility to repair a dysfunctional AV access.

Also, the potential for reducing the number of repeat procedures by more than 50% represents a huge cost savings, particularly in the U.S. health care model. “By our cursory estimate, if as few as half of the dialysis maintenance procedures were performed using this device, the U.S. Medicare system would stand to potentially save … almost half a billion dollars every year solely by avoiding unnecessary visits to the emergency room [and] unnecessary procedures to keep a dialysis access open.”

Paclitaxel

Pacyna concluded by noting that in 2019, groups were discussing the safety of paclitaxel, with the FDA even convening a two-day meeting. The advisory hearing examined the use of paclitaxel devices for the lower limbs. The FDA said in early 2019 that it would evaluate potential long-term mortality for patients receiving treatment for peripheral artery disease with paclitaxel-coated balloons and stents. That came after a meta-analysis appeared in the Journal of the American Heart Association that argued there was an increased risk of death for these patients at five years.

“What we talked about when we received approval as the first paclitaxel-coated device for a new indication … post that discussion and seeing that continue to evolve where you see these types of devices and the In.Pact platform in general has been really well received over the last year.”

Pacyna noted that Medtronic is working with the FDA and other stakeholders to drive continued work on paclitaxel safety.

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