January 9th, 2014

Pivotal Renal Denervation Trial Fails to Show Efficacy

Medtronic announced today that the SYMPLICITY HTN-3 trial of its much-anticipated  renal denervation device had failed to meet its primary efficacy endpoint. Renal denervation has been widely touted as a breakthrough product that could dramatically lower blood pressure by as much as 30 mm Hg, allowing physicians to cure the most severe form of high blood pressure, resistant hypertension.

“SYMPLICITY HTN-3 met its primary safety endpoint related to the incidence of major adverse events one month following randomization and renal artery stenosis to six months,” said Deepak Bhatt, the co-principal investigator of the trial, in the Medtronic press release. “Importantly, however, the trial did not meet its primary efficacy endpoint.” To demonstrate efficacy in the trial, blood pressure in the treatment arm would have needed to be 10 mm Hg lower than in the control arm.

Medtronic said that because no safety concerns emerged in the trial, “no specific action is currently indicated for patients who have had the renal denervation procedure with the Symplicity system.” The company said it will assemble a panel of independent advisors “to make recommendations about the future of the global hypertension clinical trial program.”  Until then Medtronic said it would suspend enrollment in ongoing trials, including the SYMPLICITY HTN-4 trial studying renal denervation in patients with less severe forms of hypertension. Symplicity will still be available in Europe and other markets where it has been approved and the company will continue its global post-market surveillance registry as well as studies that are evaluating other non-hypertension indications for the device.

Wells Fargo analyst Larry Biegelsen said that the news means that that Medtronic is unlikely to gain U.S. approval for the device without first running another trial.

Until recently the forecast for renal denervation had been extremely optimistic. More realistic expectations began to appear in 2013. Last summer, a paper published in Heart showed that the large reductions in blood pressure seen in earlier clinical trials of renal denervation were likely a product of serious flaws in the design of these trials. Until SYMPLICITY HTN-3, the renal denervation trials had been largely uncontrolled, unblinded, and had utilized office-based blood pressure measurements rather than the far more reliable and consistent ambulatory blood pressure monitoring. The senior author of the Heart paper, Darrel Francis,  predicted that “people are going to be severely disappointed” by the results of SYMPLICITY HTN-3.

In December, St. Jude confirmed that it had halted enrollment in its EnligHTN IV trial, which was the pivotal trial for its own renal-denervation device.  Renal-denervation products are currently available in Europe and elsewhere from Medtronic, St. Jude Medical, Boston Scientific, Covidien, Recor, and Terumo.




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