Medtronic is launching another rigorous clinical trial to test a minimally invasive procedure called "renal denervation" in the hopes of getting regulatory approval to launch a major new commercial market in the U.S. to treat high blood pressure.
The placebo-controlled randomized trial, approved by the U.S. Food and Drug Administration, will allow Medtronic to test its Symplicity Spyral renal denervation system on patients while they remain on blood-pressure drugs. In contrast to this "On Med" group, Medtronic is also running a pivotal trial simultaneously to look at the experiences of patients who stop taking antihypertensive drugs before getting renal denervation.
"Results from the 'On Med' trial will add to the growing body of evidence supporting renal denervation and [are] intended to support clinicians in making treatment decisions for patients who might benefit from this procedure," Dave Moeller, general manager of Medtronic's renal denervation business, said in an announcement Thursday. (Renal denervation devices are legal to sell in Europe today, but not in the U.S.)
High blood pressure, also known as hypertension, greatly increases the risks of heart attack, stroke, and heart and kidney failure. Direct costs from the condition rise to about $500 billion worldwide annually, Minnesota-run Medtronic estimates.
But outside of behavioral steps such as losing weight and cutting down on salt, the major treatments for high blood pressure in the U.S. are all prescription drugs. Medical device companies have long labored to figure out how to commercialize the medical discovery that altering overactive nerve activity between the kidneys and the brain can lower blood pressure without using drugs.
It has turned out to be a long road. Ardian Inc., the California company that Medtronic acquired for $800 million for its renal denervation system, was founded as a startup back in 2003, for example.
The Ardian device has evolved over the years, but all of the systems are based on the concept of inserting a thin electrode catheter into the renal artery and then "ablating" the nerves in the artery wall using radio-frequency energy. Cutting down on overactive signals from the kidney is supposed to trigger physiological changes that reduce blood pressure, including at night, when patients can't take their pills.
All the major cardiovascular-device companies once had renal denervation devices under development. But the commercial momentum halted in 2014, when Medtronic announced the surprising result that its sham-controlled, company-sponsored clinical trial found that people who had renal denervation had the same average drop in blood pressure as patients who received fake placebo treatments.
Rather than abandon renal denervation, Medtronic doubled down, doing an in-depth analysis of its device and patients to find out why the science wasn't translating into broadly detectable medical results. The device and the procedure were modified as a result of the analysis, and future trial patients would have their adherence to prescription drugs closely monitored as well.
That's why Medtronic is running "Off Med" and "On Med" studies on different sets of patients, after working with the FDA to design the best ways to evaluate the therapy.
"Washing patients off their meds clearly gives us the best way to find the signal that RDN [renal denervation] works," Medtronic spokesman Joey Lomicky said in an e-mail Thursday. However, "there's also an interest in determining how the procedure works in the presence of medication, which … is the population that physicians would commonly be treating in the real-world."
That's why Medtronic believes the outcomes from its "On Med" study population will be important for eventual clinical adoption, even though the "Off Med" study is considered the pivotal study that will be submitted to the FDA to get approval for the Symplicity Spyral device. Data from both studies are likely to be submitted to the FDA.
"Ultimately, the FDA will have safety data from both trials," Lomicky wrote.