Medtronic's Symplicity HTN-4 Trial Approved to Study Renal Denervation for Patients With Moderate Uncontrolled Hypertension

November 5, 2013––Medtronic, Inc. (Minneapolis, MN) announced that the US Food and Drug Administration has approved an investigational device exemption allowing the company to initiate the Symplicity HTN-4 trial to investigate renal denervation for the treatment of moderate uncontrolled hypertension in United States patients. Medtronic noted that the first patient in the trial was enrolled at Duke University Medical Center in Durham, North Carolina.

According to the company, the randomized Symplicity HTN-4 study will evaluate Medtronic's Symplicity renal denervation system in patients with moderate uncontrolled hypertension (systolic blood pressure ≥ 140 and < 160 mm Hg, despite treatment with three or more antihypertensive medications of different classes).

Symplicity HTN-4 is Medtronic's second randomized controlled renal denervation clinical trial in the United States. The Symplicity renal denervation system is currently only available for investigational use in the United States. The device received European CE Mark approval in 2008.

Medtronic stated that Symplicity HTN-4 builds upon the Symplicity HTN-3 study, which is the pivotal United States clinical trial of the Symplicity renal denervation system for the treatment of patients with uncontrolled hypertension with a systolic blood pressure ≥ 160 mm Hg. Symplicity HTN-4 will enroll up to 580 patients with systolic blood pressures ≥ 140 and < 160 mm Hg at approximately 100 sites. The trial will continue to target a patient population in line with the American Heart Association and the European Society of Hypertension shared definition of uncontrolled hypertension from the JNC-7: Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure.

Similar to Symplicity HTN-3, the Symplicity HTN-4 study will be blinded and include a sham control. Efficacy will be evaluated based on the ability of patients to either meet the goal of achieving a systolic blood pressure < 140 mm Hg or to achieve a prespecified reduction in 24-hour ambulatory blood pressure. Safety will be assessed as it is in Symplicity HTN-3 by evaluating major adverse events at 1 month and renal artery stenosis at 6 months.

David Kandzari, MD, and Michael Weber, MD, are Coprincipal Investigators of Symplicity HTN-4. Dr. Kandzari is Chief Scientific Officer and Director of Interventional Cardiology at Piedmont Heart Institute in Atlanta, Georgia. Dr. Weber is Professor of Medicine, Division of Cardiovascular Medicine, at the SUNY Downstate College of Medicine in Brooklyn, New York.

In the company's announcement, Dr. Kandzari explained, “Over the past several years, the Symplicity renal denervation system has successfully treated patients outside the United States with a more severe form of uncontrolled hypertension characterized by systolic blood pressures at or above 160 mm Hg. However, many patients with uncontrolled hypertension have blood pressures between 140 and 160 mm Hg, 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.”

Dr. Weber added, “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.”