St. Jude’s CEO is still betting on EnligHTN IV Study Renal Denervation System, despite Medtronic’s setback related to SYMPLICITY Phase IV
UPDATED on 1/14/2014
This is in continuation to our 1/9/2014 article:
Market Impact on Global Suppliers of Renal Denervation Systems by Pivotal US Trial: Metronics’ Symplicity Renal Denervation System FAILURE at Efficacy Endpoint
In the short term, the company, St. Jude suspended enrollment in three other related trials and announced plans to gather an independent panel of experts to plot a future course.
St. Jude Medical won a CE mark for its next-gen EnligHTN IV renal denervation system over the summer, but halted its own U.S. trial in December. Minnesota-based St. Jude said it had struggled to recruit viable candidates for the 590-patient trial, and was concerned that Medtronic’s Symplicity might siphon off viable patients needed for its own study. At the time, St. Jude said it would work to develop a new protocol to address trial enrollment challenges.
According to Mark Hollmer:
Symplicity’s setbacks may make that job much easier for St. Jude. They also create new opportunities for other rivals focused on developing similar technology, such as Boston Scientific ($BSX) and Covidien ($COV).
Curator of this article has expressed a different view in
St. Jude’s CEO is still betting on renal denervation, despite Medtronic’s setback
By Mark Hollmer
Medtronic’s Symplicity renal denervation device
If Medtronic’s ($MDT) recent U.S. clinical trial failure for its Symplicity renal denervation device throws the door wide open for its competitors, St. Jude Medical ($STJ) will likely waste no time walking through.
As MassDevice reported, St. Jude CEO Daniel Starks told an audience at the JPMorgan Healthcare conference in San Francisco that the company plans to keep plowing ahead with the development of its own technology.
“The fact that we had and that there have been favorable early clinical results in numerous other experiences is still valid,” MassDevice quoted Starks as saying. “There is open surgical data dating back several decades that was favorable to the impact of surgical renal denervation to treat hypertension.
That said, he also expressed genuine surprise about Medtronic’s trial setback.
“This was unexpected for us, to have a negative result from Medtronic’s trial, and it’s too soon for us to know what to make of that,” Starks said in the story.
Medtronic’s Symplicity device, which has a CE mark and is a market leader, had done well in previous trials in patients with different forms of hypertension and was on track to win FDA approval in 2015–potentially the first renal denervation device to reach that point.
The Minnesota device giant announced a few days ago that Symplicity proved safe in a 535-patient trial but failed to significantly lower blood pressure for drug-resistant hypertension.
This was a trial that mattered, designed to help fuel FDA approval.
Related Articles:
Medtronic’s flunked trial throws its hypertension program into doubt
St. Jude Medical will try again another day for a U.S. renal denervation study
St. Jude bags EU approval for next-gen renal denervation
SOURCE
From: FierceMedicalDevices <editors@fiercemedicaldevices.com>
Date: Tue, 14 Jan 2014 18:14:06 +0000 (GMT)
To: <avivalev-ari@alum.berkeley.edu>
Renal Denervation: EnligHTN IV Study Called Off and Potential Novel Indications – Diastolic Heart Failure
Reporter: Aviva Lev-Ari, PhD, RN
This Open Access Scientific Journal has covered all the major developments reported on Renal Denervation since its inception
The Archive for Renal denervation
Search Results for Renal Denervation
http://pharmaceuticalintelligence.com/?s=Renal+denervation
Heartwire Reported on December 09, 2013
EnligHTN IV Renal Denervation Study Called Off
ST PAUL, MN – The EnligHTN IV study (St Jude Medical, St Paul, MN), testing the multielectrode renal-denervation system in patients with resistant hypertension, has been stopped almost before it even began. The trial, which was announced in June and began enrolling a small number of patients this fall, was canceled because of concerns about slow enrollment.
To heartwire ,
Denise Perkins-Landry, a spokesperson for St Jude Medical, said the decision to discontinue the study was based on “anticipated recruitment challenges” and is not the result of any safety or efficacy issues with the device. “A US clinical trial for EnligHTN remains a very high priority for St Jude Medical, and we will be working with the FDA to develop a new protocol that will address anticipated enrollment challenges,” she stated in an email.
The full results of the SYMPLICITY HTN-3 trial, a study similar to the EnligHTN IV study, which is sponsored by Medtronic (Minneapolis, MN), are expected in early 2014. While neither device is approved for clinical use in the US, it is expected that the Medtronic renal-denervation system will be first. As a result, it might be difficult to enroll patients to a sham procedure if there is another commercially available system for treating resistant hypertension, according to St Jude.
EnligHTN IV was to be a randomized, single-blind, controlled study with patients randomized from as many as 80 clinical centers in the US and Canada. It was intended to show the safety and effectiveness of the renal-denervation system in the reduction of systolic blood pressure in 590 patients with an office blood pressure >160 mm Hg despite taking three or more antihypertensive medications, including a diuretic.
Abrupt Decision to Stop the Study
Dr William White (University of Connecticut Medical Center, Farmington), one of the cochairs of the EnligHTN IV steering committee, told heartwire the decision to cancel the study was made just last week. In fact, there were clinical centers already up and running in terms of enrollment, although these were pilot centers where any “bugs could be worked out.” The meeting for training investigators participating in the trial was scheduled for Saturday in Chicago, IL, although that is now off.
“In the grander scheme of things, I can tell you that the decision was not made because of any problem with the catheter or any safety issues,” said White. “Outside the US, the development is continuing as planned, but the biggest concern is that it might be very difficult, if not impossible, to continue doing a sham-controlled study a year from now if there were a commercially available renal-denervation catheter in the US, which there very well could be with Medtronic.”
Still, White said that it’s not even known if the SYMPLICITY HTN-3 study is positive or if the FDA will be satisfied with the trial and its outcomes. He said a lot of assumptions are being made by St Jude Medical in stopping the trial, and it could turn out to be a bad decision. In addition, reimbursement remains an open question.
As a scientist, White said that he would have preferred the trial be pursued, regardless of what happens with Medtronic. He believes the EnligHTN catheter is “outstanding,” as it has multiple electrodes to enable physicians to thoroughly ablate the renal arteries within a couple of minutes. “The clinical scientist in me would have preferred that we go ahead as planned,” he said. “I think we would have gained a great deal of knowledge. And just because one study shows a p value of 0.05 doesn’t mean a second study will.”
The Medtronic SYMPLICITY renal-denervation system was launched in 2010 and is available in parts of Europe, Asia, Africa, and South America. The first-generation EnligHTN device has had CE Mark approval in Europe since 2012 while the updated second-generation system with multiple electrodes received European approval this past summer.
News of the halting of EnligHTN IV was first reported by Wells Fargo analyst Larry Biegelsen.
SOURCE
http://www.medscape.com/viewarticle/817482?nlid=41903_2105&src=wnl_edit_medp_card&uac=93761AJ&spon=2
Renal Denervation’s Structural, Functional Heart Benefits May Be Independent of BP
HAMBURG, GERMANY — In a small study of patients undergoing renal denervation for resistant hypertension, left-ventricular hypertrophy and diastolic function improved independently of changes in blood pressure and heart rate [1].
“The novelty of our findings is the independence of morphologic improvements [regression of LV hypertrophy] from hemodynamic changes (reduction of blood pressure and heart rate),” Dr Stephan H Schirmer (University of Saarland, Hamburg, Germany) told heartwire in an email. “If this is confirmed in larger trials, it might open up novel indications for the use of renal denervation, for example, in [diastolic] heart-failure patients, independent of blood pressure.”
Dr Deepak L Bhatt (Harvard Medical School, Boston, MA) told heartwire that the study observations are “provocative” and “exciting” but stressed that they need to be confirmed in a blinded, larger, multicenter study before they could be accepted into clinical practice. Bhatt and Dr George Bakris (University of Chicago, IL) are co–principal investigators for the ongoing SYMPLICITY HTN-3 trial of bilateral renal denervation in patients with uncontrolled hypertension.
The study was published online December 4, 2013 in the Journal of the American College of Cardiology.
Are Renal Denervation Effects Always Tied to BP Change?
Renal denervation reduces heart rate and blood pressure in patients with resistant hypertension, and as reported by heartwire , a recent small study suggested that the procedure also reduces left-ventricular mass and improves diastolic function in such patients, Schirmer and colleagues write.
They hypothesized that renal denervation might affect cardiac structure and function, independent of the effect on blood pressure.
They enrolled 66 consecutive patients who underwent renal denervation using the Flex catheter system (Medtronic) at their center during 2010 and 2011 for treatment of resistant hypertension (office systolic blood pressure >140 mm Hg). Patients had a mean age of 64 years, and 55% were men. They were on a mean of 4.3 antihypertensive drugs. All were taking a diuretic, 89% were taking a beta-blocker, and 55% were taking an angiotensin-receptor blocker.
Six months after renal denervation,
- Mean blood pressure decreased from 172.9/92.5 to 151.3/85.5 mm Hg, confirmed by 24-hour ambulatory monitoring, if available (n=50).
- Mean heart rate decreased from 67.7 to 60.5 bpm.
- Mean left-ventricular mass index decreased from 61.5 to 53.4 g/m2.
- Measures of diastolic function also improved.
The changes in cardiac function and ventricular size were not tied to the magnitude of the blood-pressure reduction, which “suggest[s] a direct effect of the sympathetic nervous system on myocardial morphology and function,” Schirmer and colleagues write. They call for further research to investigate functional cardiovascular benefits of renal denervation beyond blood-pressure reduction.
Promising Early Benefit, Needs Confirmation
In an accompanying editorial [2], Bakris and Dr Sandeep Nathan (University of Chicago) commend Schirmer and colleagues “for providing promising early benefit of catheter-based renal denervation and for highlighting a possible blood-pressure–independent facet of this technique.” However, they caution that although the findings are “intriguing,” the study’s limitations include that it was
- relatively small,
- conducted at a single center,
- lacked a sham control, and
- relied on echocardiography rather than magnetic resonance imaging.
Therefore, “these observations need confirmation before acceptance in clinical practice . . . and can only be applied to those with inclusion criteria used in their study,” the editorialists conclude.
“Whether the reduction in left-ventricular mass is beyond what would be anticipated with blood-pressure and heart-rate reduction—certainly this analysis suggests that is a possibility—needs to be confirmed in larger studies,” he added, echoing the authors and editorialists.
Potentially referring physicians, in the United States where the procedure is investigational, and even in Europe where it’s approved, appear to be waiting for the results of SYMPLICITY HTN-3, Bhatt said. This blinded, randomized, multicenter trial will provide a clearer picture of what sort of blood-pressure reductions are achievable in patients with resistant hypertension who undergo renal denervation. Results are expected by mid-2014.
References
- Schirmer SH, Sayed M, Reil J-C, et al. Improvements of left-ventricular hypertrophy and diastolic function following renal denervation – Effects beyond blood pressure and heart rate reduction. J Am Coll Cardiol 2013; DOI:10.1016/j.jacc.2013.10.073. Abstract
- Bakris G, Nathan S. Renal denervation and left ventricular mass regression: A benefit beyond blood pressure reduction? J Am Coll Cardiol 2013; DOI:10.1016/j.jacc.2013.11.015. Editorial
SOURCE
This Open Access Scientific Journal has covered all the major developments reported on Renal Denervation since its inception
The Archive for Renal denervation
Search Results for Renal Denervation
http://pharmaceuticalintelligence.com/?s=Renal+denervation
For the ORIGINAL work on
Renal Sympathetic Denervation: Updates on the State of Medicine
the Readers is called to go to the ORIGINAL SOURCES listed below:
Intravascular Stimulation of Autonomics: A Letter from Dr. Michael Scherlag
Imbalance of Autonomic Tone: The Promise of Intravascular Stimulation of Autonomics
Interaction of Nitric Oxide and Prostacyclin in Vascular Endothelium
Absorb™ Bioresorbable Vascular Scaffold: An International Launch by Abbott Laboratories
The Molecular Biology of Renal Disorders: Nitric Oxide – Part III
http://pharmaceuticalintelligence.com/2012/11/26/the-molecular-biology-of-renal-disorders/
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