Medtronic's SYMPLICITY HTN-3 Pivotal Trial Fails to Meet Efficacy Endpoint

January 9, 2014—Medtronic, Inc. (Minneapolis, MN) announced that SYMPLICITY HTN-3 failed to meet its primary efficacy endpoint. SYMPLICITY HTN-3 is the company’s United States pivotal trial in renal denervation for treatment-resistant hypertension. Medtronic states that the trial met its primary safety endpoint, and the trial's Data Safety Monitoring Board concluded that there were no safety concerns in the study.

SYMPLICITY HTN-3 is a blinded, randomized, controlled trial designed to evaluate the safety and effectiveness of renal denervation with the investigational Symplicity renal denervation system in patients with treatment-resistant hypertension and systolic blood pressure higher than 160 mm Hg in the United States. Follow-up for all patients randomized in the trial will continue as planned out to 5 years, advised Medtronic.

In Medtronic’s press release, SYMPLICITY HTN-3 coprincipal investigators Deepak L. Bhatt, MD, and George Bakris, MD, commented on these findings.

Dr. Bhatt stated, “SYMPLICITY HTN-3 met its primary safety endpoint related to the incidence of major adverse events 1 month following randomization and renal artery stenosis to 6 months. Importantly, however, the trial did not meet its primary efficacy endpoint.”

Dr. Bakris added, “While it's disappointing the trial did not meet its primary efficacy endpoint, this is the most rigorous renal denervation clinical trial conducted to date and the first of its kind to include a sham control group. We look forward to advancing these data into the peer-review process and will submit these findings for presentation and scientific discussion at an upcoming scientific congress.”

Dr. Bhatt is Executive Director, Interventional Cardiovascular Programs, Brigham and Women's Hospital Heart and Vascular Center, and Professor of Medicine, Harvard Medical School. Dr. Bakris is Professor of Medicine and Director of the ASH Comprehensive Hypertension Center at the University of Chicago Medicine and Past President of the American Society of Hypertension.

Medtronic stated that based on these clinical trial findings, the company intends to formulate a panel of independent advisors made up of physicians and researchers who will be asked to make recommendations about the future of the global hypertension clinical trial program, as well as provide advice on continued physician and patient access to the Symplicity technology in countries with regulatory approvals. The Symplicity system has received European CE Mark approval and Australian Therapeutic Goods Administration approval. In the United States and Japan, the Symplicity renal denervation system is available for investigational use only.

Pending this panel review, the company intends to:

• Suspend enrollment in the three countries where renal denervation hypertension trials are being conducted for regulatory approvals: SYMPLICITY HTN-4 in the United States, HTN-Japan, and HTN-India.
• Begin informing clinical trial sites and investigators, global regulatory bodies, and customers of these findings and decisions.
• Continue to ensure patient access to the Symplicity technology at the discretion of their physicians in markets where it is approved.
• Continue the Global SYMPLICITY postmarket surveillance registry and renal denervation studies evaluating other nonhypertension indications.

Medtronic advised that no specific action is currently indicated for patients who have had the renal denervation procedure with the Symplicity system because of the device’s demonstrated safety profile, including the SYMPLICITY HTN-3 findings. Patients should consult with their physician regarding any questions they may have about their treatment.

In the company’s press release, Medtronic’s Chief Medical Officer Rick Kuntz, MD, stated, “We are disappointed that the clinical trial failed to meet its primary efficacy endpoint. We believe this course of action is the most prudent and will help us thoroughly evaluate these findings and determine the appropriate next steps for renal denervation therapy. We would like to thank the patients and investigators for their participation in the trial and their important contribution to the field of hypertension research.”

According to Medtronic, the SYMPLICITY HTN-3 study randomized 535 treatment-resistant hypertension patients in 87 medical centers in the United States. Patients receiving the investigational treatment were compared with a sham control group that did not receive treatment, with all patients continuing to take their blood pressure medications. Patients enrolled in the SYMPLICITY HTN-3 trial were randomly assigned to a group, with two out of three assigned to the treatment group and one out of three assigned to the sham control group. In addition, those in the control group had the option to receive the treatment after the 6-month assessment of the primary endpoint. The primary endpoints of the study are the change in office blood pressure from baseline to 6 months and incidence of major adverse events.

The SYMPLICITY HTN-3 study design was published by Dr. Bakris, et al in Clinical Cardiology (2012;35:528-535). More information for SYMPLICITY HTN-3 is also available on the website www.clinicaltrials.gov (identifier:  NCT01418261).