Medtronic (NYSE:MDT) revealed the details today of a clinical trial of its Symplicity renal denervation treatment for hypertension, but said it still plans to investigate the treatment even though the study showed only meager improvements in high blood pressure compared with a sham procedure.
In a widely anticipated presentation of data from Medtronic’s Symplicity HTN-3 trial in Washington today at the American College of Cardiology’s annual meeting, 1 of the study’s lead investigators said the renal denervation arm showed only a 2.39mm Hg reduction in systolic blood pressure after 6 months. Ambulatory systolic pressure, measured over 24 hours, was down 1.96mm Hg for the Symplicity arm. There were no significant differences in safety between the study’s 2 groups, Dr. Deepak Bhatt said.
Bhatt said physicians using the treatment where it’s approved overseas should carefully consider renal denervation for hypertension in light of the results.
"As far as clinical practice outside the U.S., I think doctors need to look at these data and honestly ask themselves, is their clinical practice so dissimilar from the patients in our trial that they would not believe a rigorously done, randomized clinical trial?" he said. "Personally, I would be cautious about offering the procedure to patients in the face of a large, randomized clinical trial."
Data on the 535 patients treated in the study, also published today in the New England Journal of Medicine, showed that the mean reduction in systolic pressure after 6 months was 14.13mm Hg for the RDN-treated arm and 11.74mm Hg for the sham arm.
Medtronic said it still plans to pursue renal denervation for resistant hypertension, backed by recommendations from an independent panel of experts.
"Based on the unique nature of these findings and support from the independent panel that additional research be considered to better understand the effects of the Symplicity technology for renal denervation, we remain convinced that resistant hypertension is a large unmet medical need and renal denervation remains a promising opportunity," Medtronic’s renal denervation general manager Nina Goodheart said in prepared remarks.
Medtronic said the panel approved its plans to shut down its Symplicity HTN-4 trial, which it suspended along with trials in India and Japan in January. The company will consult with those countries about whether to re-start the HTN-Japan and HTN-India studies, according to the release. The Symplicity RDN treatment for hypertension will still be offered in jurisdictions where it’s approved and Medtronic will continue to enroll patients in a global registry, the company said.
"Medtronic will continue to provide access to the Symplicity system in countries where it has regulatory approval and will continue to support a global hypertension clinical program," according to the release. "Based on our detailed analysis of Symplicity HTN-3, we believe further clinical investigation is warranted; Medtronic will determine the optimal path forward, along with FDA, for the next U.S. [investigational device exemption]."
And Medtronic will "continue to pursue its studies in other disease states, including atrial fibrillation, chronic kidney disease, heart failure, etc.," according to the release.
Medtronic’s chief medical officer, Dr. Rick Kuntz, said the company is evaluating "many factors that may have contributed to the observed efficacy results beyond the employment of a more rigorous trial design."
"There are several differences between the Symplicity studies, including the populations studied, required medication dosing, patient behaviors in terms of lifestyle and drug adherence, and potential for procedural variability. We are evaluating the contributions of these potential factors, which are hypothesis-generating and will guide us in determining the path forward with FDA," Kuntz said in a statement.
Medtronic’s announcement of Symplicity HTN-3’s efficacy failure in January shocked medtech, prompting suspension of enrollment in other Symplicity trials around the world and sparking other major players to suspend their hypertension RDN programs or even abandon the field altogether. For its part, Medtronic has said that a writedown of its renal denervation assets is likely.
How the Symplicity HTN-3 data will affect other companies invested in renal denervation technology is not yet clear. Rival RDN players Boston Scientific (NYSE:BSX) and St. Jude Medical (NYSE:STJ) in January declared that they’re not willing to dump their development efforts just yet, speculating that the technology used in Medtronic’s trial is substantially different from either Boston Scientific’s Vessix or St. Jude’s Enlightn.
Previously, fearing that Medtronic’s Symplicity device would already be on the market, St. Jude had called off the Enlightn IV trial of the next generation of its renal denervation technology in December, just a few months after it began, over concerns that it would be tough to enroll patients in a trial in which they could end up in the sham arm when another device with similar technology was already on the market. The trial of St. Jude’s multi-electrode Enlightn device was slated to enroll about 590 patients between the ages of 18 and 80 with high blood pressure that isn’t well-managed with drugs.
An unnamed co-principal investigator in Medtronic’s Symplicity HTN-3 trial in January said the results may signal the end of the technology because the efficacy failure was based on renal denervation as an approach to treat hypertension, rather than on the device. Cardiologist Dr. Darrel Francis predicted the HTN trial failure in a research paper published last year, but defended renal denervation as a treatment for hypertension, just with a smaller benefit than originally hoped for in a January interview with MassDevice.com. The technology could still make a big difference for patients, he said.
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