Medical Device Daily Senior Staff Writer

Medtronic (Minneapolis) reported the start of SYMPLICITY HTN-3, the U.S. trial of its Symplicity renal denervation system for treatment-resistant hypertension. The first patient in this landmark study was enrolled at the Prairie Heart Institute at St. John's Hospital (Springfield, Illinois).

Renal denervation is a minimally-invasive, catheter-based procedure that modulates the output of nerves that line the walls of the arteries leading to the kidneys. The targeted nerves are part of the sympathetic nervous system, which has been found to play a central role in blood pressure regulation.

"Patients with hypertension and the physicians who treat them are excited about this technology because it holds the promise of addressing a subset of hypertension called treatment-resistant hypertension," Joe McGrath, a Medtronic spokesperson, told Medical Device Daily.

Treatment resistant hypertension, defined as persistently high blood pressure despite three or more antihypertensive medications of different types, puts nearly 120 million people worldwide at risk of premature death from kidney disease and cardiovascular events such as stroke, heart attack and heart failure, Medtronic noted.

Catheter-based renal denervation to control resistant hypertension is considered among heart doctors to be such a transformative technology that it landed in the number one spot of the Cleveland Clinic's Top 10 Medical Innovations for 2012, which was released earlier this month during the organization's annual Medical Innovation Summit (Medical Device Daily, Oct. 7, 2011).

"Renal denervation has the potential to extend the lives of millions of people who suffer from treatment-resistant hypertension," said Krishna Rocha-Singh, MD, medical director of the Prairie Vascular Institute and the Prairie Education and Research Cooperative. "Based on the results of prior clinical studies and contemporary clinical practice, this interventional technique could be one of the most significant advances in our approach to addressing this insidious disease to be developed in decades."

SYMPLICITY HTN-3 is a randomized controlled trial designed to evaluate the safety and effectiveness of renal denervation with the Symplicity renal denervation system in patients with treatment-resistant hypertension. Medtronic says the study will enroll about 530 treatment-resistant hypertension patients across 60 U.S. medical centers. All patients and hypertension follow-up assessors will be blinded to the randomization assignments to remove any potential for bias. The primary endpoints of the study are the change in blood pressure from baseline to six months and incidence of major adverse events up to six months following randomization.

The Symplicity renal denervation system consists of a generator and flexible catheter. The Symplicity catheter is introduced through a separate catheter placed through the skin into the femoral artery, located in the upper thigh, and is then threaded up into the renal artery leading to each kidney. It is connected to the Symplicity generator, which produces low-power radio-frequency (RF) energy.

Once in place within the renal artery, the tip of the Symplicity catheter is placed against the arterial wall in several places where it delivers RF energy to the surrounding sympathetic nerves according to a proprietary, computer-controlled algorithm. The treatment does not involve a permanent implant and is performed under conscious sedation.

The Symplicity system has been used since 2007 to treat more than 2,000 patients worldwide. It has been available in Europe and Australia since April 2010. The FDA granted Medtronic approval for the SYMPLICITY HTN-3 protocol earlier this year (MDD, July 13, 2011).

Clinical research to date shows that renal denervation with the Symplicity system may provide a significant and sustained reduction in blood pressure levels for many patients with treatment-resistant hypertension. Published in The Lancet late last year, results from SYMPLICITY HTN-2, a randomized, controlled trial of 106 patients in Europe and Australia, showed that patients with treatment-resistant hypertension randomized to renal denervation achieved a mean blood pressure reduction of 32/12 mmHg (millimeters of mercury) at six months, whereas the patients in the control group randomized to anti-hypertensive medications alone had blood pressures that did not vary from baseline (1/0 mmHg). The overall occurrence of adverse events did not differ between groups, the company noted.

"Medtronic is leading the development of this technology," McGratah said. "Other companies have begun preliminary feasibility studies for other renal denervation systems but Medtronic is far ahead [of the competition]."

St. Jude Medical's (St. Paul, Minnesota) renal denervation catheter and generator system is being used in a feasibility study at the Royal Adelaide Hospital in South Australia (MDD, Oct. 20, 2011). St. Jude expects to eventually launch the product in the U.S. but a company spokesperson told MDD that "no timelines have been disclosed" and for now the company is focused on Europe and expects a limited launch of the device in Europe before the end of 2012.

Cleveland Clinic experts noted during the Medical Innovations Summit that renal denervation also shows promising results for treating chronic kidney disease, insulin resistance, and heart failure. McGrath said some of these other potential indications are of interest to Medtronic.

He also pointed out that not all patients with treatment-resistant hypertension will be appropriate candidates for this technology. For example, if a patient has two or more renal arteries feeding an individual kidney they are not currently eligible for the treatment, he said.

That makes it tough to put a number on the estimated market size for the technology. McGrath said the company estimates that roughly 1.5 billion people worldwide will have hypertension by 2025 and somewhere between 30% and 50% of those patients who are being treated will remain uncontrolled by traditional drug therapy. Based on that understanding, Medtronic projects that about 4 million patients in the U.S., 4 million in Japan, and 5 million in Europe would be candidates for catheter-based renal denervation. Another factor that should not be underestimated, McGrath said, is the impact that reimbursement will have on the uptake of the technology.

Medtronic acquired the Symplicity technology late last year through its $800 million purchase of Ardian (Mountain View, California), the company that developed the system (MDD, Dec 1, 2010).

At the time of the Medtronic-Ardian deal, Wells Fargo Securities (San Francisco) analyst Larry Biegelsen predicted that the catheter-based renal denervation market could reach the $3 billion mark by 2020, with Medtronic maintaining a 60% market share.

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