Taking aim at the costly problem of high blood pressure, Medtronic is launching the first placebo-controlled large-scale clinical study of a medical device treatment intended to lower a person's blood pressure without medication by interrupting nerve activity.
The therapy is called "renal denervation," and it involves inserting a Medtronic catheter into the artery that feeds the kidneys to burn away some nerves in the vessel tissue that help drive overactive nervous impulses and cause high blood pressure. Hypertension increases heart attack and stroke risks, and it creates $500 billion in annual direct costs globally.
Unlike past large studies of renal denervation, Medtronic's Spyral HTN Pivotal Trial will require that its 433 patients at 50 sites not be on drugs to treat their hypertension before or after they get the procedure.
The new trial also uses a redesigned Medtronic catheter that is shaped like its namesake spiral and informed by a deeper understanding of renal blood vessel anatomy. The device doesn't destroy all of the nerves in the blood vessel, but it destroys enough of them to create a clinically meaningful change in nervous activity, a spokesman said.
Medtronic funded a previous trial of renal denervation that ended in a high-profile failure in 2014 — an outcome that quelled interest in renal denervation industrywide and placed question marks around Medtronic's $800 million acquisition of renal denervation device maker Ardian in 2011.
Known as Symplicity HTN-3, that previous trial employed stricter scientific controls than earlier studies, including having a placebo group for patients who underwent a sham procedure without having renal nerves ablated. Patients who underwent the procedure with or without nerve ablation later experienced similar levels of blood pressure reduction.
Rather than abandon the idea and write off the loss, Medtronic conducted fresh basic research on its device, renal anatomy, and how doctors performed the procedure.
One key confounding factor in all the prior studies turned out to be whether patients took high blood pressure drugs as prescribed, which could have affected trial outcomes but had nothing to do with denervation.
The result of the re-examination was two new proof-of-concept trials announced in 2016: one that used Medtronic's new Spyral device with patients who were taking blood pressure drugs, and a second trial that used the same device but required patients to go off the drugs for three weeks and then stay off for three months after the procedure.
Both studies used placebo controls. The Spyral "On-Med" proof-of-concept trial is still ongoing, with results expected in May.
However, the results of the Spyral "Off-Med" pilot study were published last November in the Lancet. The "off-med" patients saw an average 10-point reduction in systolic blood pressure as measured in a doctor's office, compared to a 2.3-point reduction for the placebo patients. (Diastolic pressure dropped 5.3 points in the treatment arm, and 0.3 in the control group.)
Following publication of those results, the Food and Drug Administration approved the larger study of the "off-med" patients that Medtronic announced on Monday. If the results are positive, Medtronic intends to present the data to the FDA to get the Spyral device approved in the U.S.
"The pivotal trial is but one part of the broader Spyral HTN Global Clinical Program and we envision this package of data will ultimately support the approval submission," Medtronic spokesman Joey Lomicky said via e-mail Monday.
With the "on-med" study still ongoing, Lomicky said it's not yet clear which groups of patients might end up in the intended patient populations.
"While we remain confident that the Spyral HTN On-Med study will also demonstrate a treatment effect with the Symplicity Spyral system, the patients potentially indicated for the Spyral procedure at the time of approval [are] not yet known," Lomicky said.