That’s because physicians there, where the procedure is approved, have come to rely on it to treat patients whose high blood pressure doesn’t respond to medications. But the rigorous structure of the Symplicity-3 trial, which included a sham control arm, set a high bar for future studies.
The Symplicity HTN-3 study, largely expected to be a slam dunk for Medtronic, failed to meet the efficacy endpoint in a U.S. pivotal trial. The news sent a shock wave through the medical device world, prompting Covidien (NYSE:COV) to ditch its RDN program. The 2 other major players in the RDN space, Boston Scientific (NYSE:BSX) and St. Jude Medical (NYSE:STJ), lowered their financial expectations for their RDN offerings, the Vessix and EnLightn devices, respectively.
But now, as evidenced by the 1st RDN trial since Symplicity-3, there is renewed interest in renal denervation for hypertension from both the medtech industry and physicians.
"Last year everyone was riding on the coat tails of Medtronic," ReCor Medical founder & COO Mano Iyer told European Hospital. "Now the playing field has been levelled and we all have an opportunity to differentiate with what we believe is a superior technology."
"If you talk to European physicians, they will tell you that a sham control may be scientifically important but not clinically relevant and that practically it is very difficult," Iyer said. "They are not believers here in Europe that a sham is necessary. They will ask how they can ethically prescribe a sham procedure if there is a procedure for a patient coming in who is suffering, with no alternatives. They will tell you this patient is going to come back with a significant cardiovascular event if we don’t get their blood pressure down. Meanwhile here is a technique that is proven to be safe that might help."
But RDN for high blood pressure is "too interesting and too young to be written off" despite the fact that "[s]ham-control arms will be a real problem in Europe," according to Dr. Felix Mahfoud of the Saarland University Hospital in Homburg, Germany.
"We see the results of [Symplicity-HTN 3] as neutral, and after a careful assessment of this study have identified various potential procedural and methodological considerations that could partly account for the study’s results," Mahfoud said.
"Moving forward with renal denervation means 2 things," added Dr. Roland Schmieder of the University of Erlangen in Germany. "First, we need to move forward with more robust study designs. It does not need to have sham-control, but it does need to be randomized with a real control group.
"As for the technology, we have heard of new technologies for a more reliable delivery of the energy, such as ultrasound, or 360-degree radiofrequency. What will become important are technologies for making the procedure less operator-dependent with reproducible effects. We are not there yet," Schmieder said.
Medtronic will keep at it with its Symplicity device, seeking answers from the Symplicity-3 data, renal denervation general manager Nina Goodheart told the journal via email.
"We are continuing our analyses of Symplicity HTN-3 and are committed to better understanding the confounding factors observed in this trial. We believe there are many factors that may have contributed to the observed efficacy results in Symplicity HTN-3, including key variables that have arisen such as population differences and medication and procedural variability in Symplicity HTN-3 versus other Symplicity studies," Goodheart wrote.
St. Jude is also "committed to this space," corporate relations vice president Rachel Ellingson told European Hospital.
"True innovation takes time and persistence to develop," Ellingson said. "The good news is that industry, academics and regulators are interested in talking about how to develop evidence that is supportive of the therapy, and whether new trial designs might help bring this therapy to patients with severe high blood pressure."