Renal denervation on razor's edge ahead of trial results
It is the quiet before the storm. At the end of March, the future of renal denevation will be decided with the presentation of the Simplicity HTN-3 clinical trial at the American College of Cardiology meeting in Washington.
Over the past two years an industry-led bandwagon for renal denervation has been rolling across European and American cardiology meetings promising that resistant hypertension can be effectively treated with a mechanical intervention to ablate nerve endings in the renal artery as an alternative to the billions of dollars spent each year on pharmaceutical remedies.
It all came to a came to a screeching halt with the announcement by Medtronic (Minneapolis) in January, 2014 that its pivotal United States trial failed to meet the primary endpoint for efficacy.
"It is still early days," said Jim Reekers, M.D., during his presentation at ECR during the session, "Renal artery denervation in the management of resistant hypertension."
"It is a promising technique, it is a safe technique. We know from the patho-physiology that it should work. We have evidence, but not too much. We have contradictory evidence now from what appears to be a pretty good trial. For the moment, we are in troubled waters," he explained, updating the scattered participants.
Professor of interventional radiology at the University of Amsterdam and former president of the Cardiovascular and Interventional Radiological Society of Europe (CIRSE), Reekers joined with fellow presenters in assessing the fallout from the Medtronic announcement.
Asked what they will be seeking in the HTN-3 results at the end of March, Reekers replied "As a scientist, I will be looking for a critical appraisal of the trial. If it measures up to those standards, I think we are done."
"I know industry is going to be looking for something else, trying to shoot holes in this trial," he said.
Asked if he meant the company that paid for the HTN-3 study would attempt to destroy their own study, Reekers said, "Yes. That is essentially it. Medtronic has been responsible in bringing out the press release. And it is important to remember that even Medtronic does not know the real causes of missing the efficacy end point, has no idea of what the data are because it is truly an independent trial."
Marc Sapoval, M.D., is a professor of Clinical Radiology and Chairman of Cardio-Vascular Radiology at the Hôpital Européen Georges Pompidou (Paris). He is also the lead investigator for the DENER-HTN Renal Denervation in Hypertension study of 120 patients over 36 months that will be published in June, 2014. The trial included a randomized arm for bilateral renal denervation using Medtronic's Symplicity catheter.
"I have no special information [about HTN-3] but I believe there will be negative results from the way it will be analyzed," he replied. "I suspect in the sham control arm the patients probably took their drugs and their level of blood pressure decreased more than was expected. I also believe that technology matters, so perhaps some other devices will be more effective. As I showed in my presentation the depths of the renal nerves require a penetration depth of up to six millimeters, so that if ablation was only two millimeters, it may not have been effective enough."
"This is only one trial, it will not close the topic." he continued. "Yet this is a very high risk field for companies. We saw the example of Covidien, which was very deeply involved. They simply shut down all their work because of investment issues. They expected that with positive HTN-3 results they could just follow behind and win FDA approval for their device in two years. Now the return on investment is not there any more because the FDA is not ready to accept these devices."
Gerard Goh, M.D., is an Interventional and Diagnostic Radiologist at St George's Hospital in London who presented a sweeping review of approved and proposed devices for renal denervation.
"There are a lot of unanswered questions about the HTN-3 trial design," he said. "Among the other companies the amount of speculation is enormous. Patients received drugs for free, for example. Previously they had to pay for the drugs and were probably non-compliant with medications. There was also a mix of ethnicity due to an FDA requirement that patients represent the U.S. population. There are so many factors that may have biased or influenced the results."
There may be a benefit to a negative result, he suggested, saying, "If renal denervation does not prove to be efficacious in what was a relatively well-designed trial, then all other companies that have invested so much will now need to design their own trials accordingly and we are going to get a much better idea of renal denervation as a whole."
According to Reekers, "Now that the field of renal denervation is open, whatever the level of evidence that is available at this moment, there will be a solution. The market is opened and we have not seen the last of the innovation and ingenuity people are exploring."
09.03.2014
