The U.S. Food and Drug Administration has approved a Medtronic medical balloon coated with the much-debated antiproliferative drug paclitaxel for patients in end-stage kidney failure who use a special vascular-access site called an arteriovenous (AV) fistula to clean their blood.
Medtronic announced Thursday that the FDA has approved its IN. PACT AV drug-coated balloon (DCB) for kidney-failure patients after a randomized, controlled trial of 330 patients found the device reduced the need for repeat operations, while maintaining the same mortality and adverse-events rates as the therapy without the drug.
“The FDA approval of IN. PACT AV DCB marks a significant step forward for paclitaxel-coated devices,” said Mark Pacyna, general manager of Medtronic’s peripheral vascular business, in the announcement. “Importantly, it allows us to expand our proven IN. PACT DCB platform beyond the superficial femoral artery” in the upper leg.
The IN. PACT AV DCB is one of the first paclitaxel-coated medical devices to gain FDA approval since the agency began investigating safety questions about devices that apply paclitaxel to clogged vessels above the knee in the legs, to treat peripheral artery disease (PAD).
Originally used in chemotherapy, paclitaxel is applied to medical devices used in blood vessels to reduce the risk that mechanically opened vessels will quickly re-close again. After reviewing medical evidence this year, the FDA said in August that PAD patients should be told about the potential for the drug to carry a higher mortality risk after five years, as well as its proven ability to keep the target vessel open more reliably than the same procedure without it.
While the debate over paclitaxel-containing devices like Medtronic’s IN. PACT Admiral DCB for PAD was ongoing, Medtronic was separately running its 330-patient clinical study to test the similar IN. PACT AV balloon on fistulae in kidney-failure patients.
Kidneys remove excess water and waste products from the blood. People with the most severe form of chronic kidney disease (often called end-stage renal disease) require an external machine to pump out and clean their blood before pumping it back in, a process known as “dialysis.”
Getting regular dialysis treatments involves pumping a lot of blood into and out of the body, putting strain on blood vessels over time. Some long-term dialysis patients opt to have a surgically created “fistula” that connects a vein to an artery, typically in the forearm. The AV fistula causes a bulge under the skin as the vessel widens, making it easier to place dialysis needles and for the blood to quickly pass through a dialyzer and back into the body.
But AV fistulae can narrow over time, requiring as many as three “maintenance procedures” per year, Medtronic’s product announcement said Thursday.
An IN. PACT balloon is a long, skinny medical device that is precisely inflated inside the vessel to reopen it. The paclitaxel on the outside of the balloon is absorbed into the vessel wall to inhibit the biological process that leads to vessel re-closure.
The 330-patient IN. PACT AV Access trial found that among patients in the U.S., Japan and New Zealand who were randomized to get either a paclitaxel-coated device or plain angioplasty on their AV fistula, patients who had paclitaxel had 56% fewer re-operations through seven months. Both groups had the same 30-day rate of serious adverse events, at 4%, and a one-year survival rate of about 90%.
After 7 months, about 81% of the patients randomized to the paclitaxel device had the target vessels remain open, or “patent,” compared to 59% in the control arm.
“Until now, there were virtually no therapies available to treat AV fistulae lesions that had demonstrated an ability to maintain primary patency and reduce reinterventions over time,” said a statement from Dr. Robert Lookstein, a surgeon with Mt. Sinai Health System in New York who is a Medtronic consultant and U.S. principal investigator for the AV Access study.