Medtronic, Inc. (NYSE: MDT), announced today that the U.S. Food and Drug Administration (FDA) has approved an Investigational Device Exemption (IDE) allowing the company to initiate SYMPLICITY HTN-4, the first randomized trial to investigate renal denervation for the treatment of moderate uncontrolled hypertension in U.S. patients.  The study will evaluate the Symplicity(TM) renal denervation system in patients with moderate uncontrolled hypertension (systolic blood pressure greater than or equal to 140 and less than 160 mm Hg, despite treatment with three or more anti-hypertensive medications of different classes). SYMPLICITY HTN-4, which enrolled its first patient at Duke University Medical Center, is Medtronic's second randomized, controlled renal denervation clinical trial in the United States. The Symplicity renal denervation system is currently available only for investigational use in the United States.

"SYMPLICITY HTN-4 builds upon our rigorous clinical evaluation of the Symplicity renal denervation system designed to carefully and progressively develop the clinical evidence platform for the treatment of hypertension," said Nina Goodheart, Vice President, General Manager, Renal Denervation, Medtronic. "We're excited to initiate this study, even while patient follow-up continues in our pivotal U.S. clinical trial for patients with uncontrolled hypertension who have systolic blood pressure at or above 160. The SYMPLICITY HTN-4 trial will allow us to potentially extend the benefits of renal denervation to patients with more moderate uncontrolled hypertension in the United States."

Approximately 120 million people with high blood pressure worldwide are considered to have uncontrolled hypertension, with systolic blood pressures at or above 140 mm Hg, despite all efforts to control blood pressure with both lifestyle and medical management strategies.^[1],[2],[3]In the United States, only approximately 60 percent of hypertension patients taking medicine have their disease under control.^[4] Uncontrolled hypertension is associated with a hyperactive sympathetic nervous system and is directly linked with a high risk of heart attacks, stroke, heart failure, kidney disease and death.Error: Reference source not found Most patients living with uncontrolled hypertension are prescribed three to five classes of anti-hypertensive medications, which can equate to taking 10 or more pills each day and are subsequently subjected to numerous side effects that may negatively impact quality of life.

"Over the past several years, the Symplicity renal denervation system has successfully treated patients outside the U.S. with a more severe form of uncontrolled hypertension characterized by systolic blood pressures at or above 160 mm Hg," explained David Kandzari, M.D., Co-Principal Investigator of SYMPLICITY HTN-4 and Chief Scientific Officer and Director of Interventional Cardiology, Piedmont Heart Institute, Atlanta, Ga.  "However, many patients with uncontrolled hypertension have blood pressure between 140 and 160 mmHg, making this also a very important group to study, since we know the risk for cardiovascular mortality and morbidity increases linearly for every millimeter of systolic blood pressure elevation above 140."

SYMPLICITY HTN-4 builds upon the SYMPLICITY HTN-3 study, Medtronic's pivotal U.S. clinical trial of the Symplicity renal denervation system, which is evaluating patients with uncontrolled hypertension having a systolic blood pressure greater than or equal to 160 mm Hg. SYMPLICITY HTN-4 will enroll up to 580 patients with systolic blood pressures greater than or equal to 140 and less than 160 mm Hg at approximately 100 sites, continuing to target a patient population in line with the Joint National Committee on the Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC-7), the American Heart Association and the European Society of Hypertension's definition of uncontrolled hypertension. Similar to SYMPLICITY HTN-3, the study will be blinded and include a sham control. Efficacy will be evaluated based on the ability of subjects to either meet the goal of achieving a systolic blood pressure below 140 mm Hg or to achieve a pre-specified reduction in 24 hour ambulatory blood pressure. Safety will be assessed as it is in SYMPLICITY HTN-3 by evaluating major adverse events at one-month and renal artery stenosis at six months. For more information about SYMPLICITY HTN-4, please go to www.symplifybptrial.com.

"This highly-anticipated, robust study will serve a key role in evaluating renal denervation in these underserved patients with less severe hypertension so that we're able to understand what benefit this novel therapy may offer patients outside of the currently indicated patient population," said Michael Weber, M.D., Co-Primary Investigator of SYMPLICITY HTN-4 and Professor of Medicine, Division of Cardiovascular Medicine, at the SUNY Downstate College of Medicine in Brooklyn, N.Y.