The Pipeline

Recent renal denervation trial fails to meet primary efficacy endpoint: What now?

Vanessa Lo, Technology Insights

Last week, Medtronic announced the major results of SYMPLICITY HTN-3, its U.S. pivotal trial for their renal denervation system for treatment-resistant hypertension. The large multi-center, randomized, controlled study was designed to assess the efficacy of the procedure by including a control arm that underwent a sham procedure. 

While the study met its primary safety endpoint, it failed to meet its primary efficacy endpoint, a sustained reduction in systolic blood pressure at six months.

In the United States, the FDA has yet to approve a renal denervation system. Cardiovascular experts anticipated that Medtronic’s Symplicity device would be the first to receive FDA approval given its clinical trial progress. However, with the negative results of SYMPLICITY HTN-3, the future of Medtronic’s Symplicity is uncertain, as well as renal denervation for treatment of hypertension.

Many unanswered questions and concerns remain for the future of renal denervation. We address four major questions below:

What does this mean for Medtronic’s device?

Medtronic announced they will assemble a panel of independent advisors to make recommendations about the future of the global hypertension clinical trial program. Until the panel review, Medtronic plans to:

  • Suspend enrollment in the three countries where renal denervation hypertension trials are being conducted for regulatory approvals, including SYMPLICITY HTN-4 in the U.S.
  • Continue the Global SYMPLICITY post-market surveillance registry and renal denervation studies evaluating other non-hypertension indications

As Medtronic has yet to release the majority of the data from the SYMPLICITY HTN-3 trial, it is difficult to determine why renal denervation failed to produce the results that many had expected based on previous studies. The principal investigators plan to share the full results at the American College of Cardiology Conference this coming March. Technology Insights will in attendance and will report results from the trial.

What about the other devices in the pipeline?

While it is too soon to make the conclusion in absence of the full study results, it is possible that different renal denervation systems may be more effective in the treating hypertension.

In addition to Medtronic’s Symplicity device, there are a number of other vendors, such as St. Jude Medical, Boston Scientific, and Covidien, in different stages of device development. Vendors scaled back their renal denervation development due to anticipated recruitment difficulties as Medtronic’s Symplicity device neared the market. In December 2013, St. Jude Medical decided to terminate the EnligHTN IV trial, the U.S. trial for their renal denervation system after enrolling fewer than 10 patients.

However, in light of Medtronic’s announcement, many vendors developing renal denervation systems remain optimistic and committed to their technology’s potential in treating hypertension. In particular, St. Jude emphasized that they will continue with its renal denervation initiatives, but have yet to announce whether they will resume the EnligHTN IV trial.

What does this mean for European countries that have renal denervation systems approved?

Currently, Medtronic’s Symplicity device is used to treat resistant hypertension across Europe. It will still be available in Europe and other markets where it has been approved. In addition to Medtronic’s device, there are five other CE marked renal denervation devices. 

In 2013, the European Society of Cardiology (ESC) issued a consensus statement on the use of renal denervation for the treatment of high blood pressure, stating that it can be considered a therapeutic option in patients with drug-resistant hypertension.

In light of Medtronic’s announcement, the ESC will reevaluate renal denervation's role once SYMPLICITY HTN-3’s results are published.

What does this mean for hospitals hoping to offer the intervention?

Over the past few years, hospitals and interventionalists have expressed strong interest in adopting renal denervation to treat the large, growing hypertension population and differentiate themselves from their local competitors. 

With enrollment in SYMPLICITY HTN-4 suspended, hospitals looking to participate in a renal denervation trial will need to consider other clinical trials. 

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