Medtronic indicated that the company is willing to support another renal denervation trial after seeing a glimmer of hope in subgroup analyses of patients with resistant hypertension. The lead investigator of the failed SYMPLICITY HTN-3 encouraged proponents to persevere, but with caution.
“We need to be honest and concede that the overall trial did not meet its primary endpoint,” Deepak L. Bhatt, MD, MPH, of Brigham and Women’s Hospital Heart and Vascular Center in Boston, told Cardiovascular Business. “Safety was established, which is useful for further future investigations but we didn’t see any efficacy overall.”
SYMPLICITY HTN-3 was a prospective, blinded, randomized, sham-controlled trial, with treatment-resistant patients receiving either renal denervation therapy with Medtronic’s Symplicity catheter or renal angiography as the sham control. The results, released on March 29 at the American College of Cardiology (ACC) scientific session in Washington, D.C., showed a decrease in blood pressure in the denervation group of 14.13 mm Hg vs. 11.74 in the sham group at six months, short of the margin of 5 mm Hg needed to establish superiority. The difference in ambulatory systolic blood pressure was -1.96 mm Hg.
A prespecified subgroup analysis favored denervation in some subgroups. Bhatt cautioned about reading too much in subgroup analyses in a negative trial, saying the statistical validity may be tenuous and that the findings needed more in-depth analysis. Any subgroup analysis results would by hypothesis-generating only.
“History has taught us that sometimes a subgroup analysis is reproducible and many times it isn’t,” Bhatt said. “We need to be cautious before we get too excited about some positive signals. But there are some positive signals there.”
Bhatt said Medtronic had conducted its own analyses on procedures and subgroups as well. The Wall Street Journal reported and Cardiovascular Business confirmed that a company executive said they planned to move forward. “We’ve seen enough positive clinical signals that this therapy warrants further investigations,” Nina Goodheart, Medtronic’s vice president of renal denervation, was quoted as saying. “Are we willing to invest in another trial? Yes.”
In contrast to SYMPLICITY HTN-3, the Global SYMPLICITY Registry results presented on March 30 reported a six-month drop in office blood pressure of 11.9 mm Hg for all patients compared with baseline and a drop in ambulatory systolic blood pressure as well. Lead investigator Michael Böhm, MD, PhD, of the University of Saarland in Homburg, Germany, in a comparison of the two studies, said SYMPLICITY HTN-3 included an African-American population and the registry did not, which he suggested may be a factor in the differing results.
In a release issued March 29, Medtronic stated it would “determine the optimal path forward, along with FDA, for the next U.S. IDE (investigational device exemption).” The company said it would continue to enroll patients in the global registry but it would shutter the SYMPLICITY HTN-4 trial.