Clinical Trials on Transcatheter Aortic Valve Replacement (TAVR) to be conducted by American College of Cardiology and the Society of Thoracic Surgeons

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Clinical Trials on Transcatheter Aortic Valve Replacement (TAVR) to be conducted by American College of Cardiology and the Society of Thoracic Surgeons

February 12, 2013 by 2012pharmaceutical

Clinical Trials on Transcatheter Aortic Valve Replacement (TAVR) to be conducted by American College of Cardiology and the Society of Thoracic Surgeons

Curator: Aviva Lev-Ari, PhD, RN

UPDATED on 6/22/2017

by Nicole Lou, Reporter, MedPage Today/CRTonline.org June 21, 2017

Action Points

Off-label transcatheter aortic valve replacement (TAVR) was associated with higher in-hospital, 30-day, and 1-year mortality rates compared with on-label TAVR use, but after adjustment, 1-year mortality was similar in the two groups.
Note that approximately one in 10 TAVR patients in the United States have received the procedure for an off-label indication.

SOURCE

1 in 10 TAVR Procedures Done Off-Label Despite early risks vs on-label use, ‘acceptable results’ cited from registry

Reviewed by Henry A. Solomon, MD, FACP, FACC Cinical Associate Professor, Weill Cornell Medical College and Dorothy Caputo, MA, BSN, RN, Nurse Planner

https://www.medpagetoday.com/Cardiology/CHF/66173?xid=nl_mpt_DHE_2017-06-22&eun=g99985d0r&pos=1

Primary Source

JAMA Cardiology

Source Reference: Hira RS, et al “Trends and outcomes of off-label use of transcatheter aortic valve replacement: insights from the NCDR STS/ACC TVT Registry” JAMA Cardiol 2017; DOI: 10.1001/jamacardio.2017.1685.
Secondary Source

JAMA Cardiology

Source Reference: Joynt KE and Kramer DB “Off-label use of high-risk cardiovascular devices: widening the lens” JAMA Cardiol 2017; DOI: 10.1001/jamacardio.2017.1732.
Additional Source

JAMA Cardiology

Source Reference: Califf RM “Evaluating evolving technologies in a time of rapid change: the case of transcatheter aortic valve replacement” JAMA Cardiol 2017; DOI: 10.1001/jamacardio.2017.1733.

UPDATED on 11/24/2013

Second Generation Transcatheter Aortic Valve Shown to Successfully Address TAVR Complications

Results of the REPRISE II trial reported at TCT 2013

November 4, 2013

heart valve repair hybrid or cath lab reprise II boston scientific lotus tct

November 4, 2013 — In a clinical trial of the Boston Scientific Lotus valve, a second-generationtranscatheter aortic valve, the device demonstrated low rates of complications that are sometimes seen in transcatheter aortic valve replacement (TAVR), including challenges with positioning, post-procedure paravalvular aortic regurgitation, vascular complications and stroke.

The findings were presented at the 25th annual Transcatheter Cardiovascular Therapeutics scientific symposium (TCT 2013).

The valve studied in REPRISE II is fully retrievable and repositionable with an adaptive seal intended to minimize paravalvular regurgitation, a complication that has been associated with higher mortality among patients undergoing TAVR. In this prospective, single-arm, multicenter study, symptomatic patients at high risk for surgery received the Lotus valve to treat calcific aortic stenosis.

The trial enrolled 120 patients; mean age was 84.4±5.3 years, 56.7 percent were female and 75.8 percent were considered New York Heart Association (NYHA) Class III or IV. The mean Society of Thoracic Surgeons score was 7.1±4.6 percent and all patients were confirmed by their site heart team to be at high risk for surgery due to frailty or associated comorbidities.

The valve was successfully implanted in all 120 patients with valve repositioning and retrieval performed as needed. There was no embolization, ectopic valve deployment or need for implantation of a second prosthetic valve.

The primary device performance endpoint was the mean aortic valve pressure gradient at 30 days compared to a performance goal of 18 mmHg; the primary safety endpoint was 30-day mortality. The primary device performance endpoint was met with a 30 day mean aortic valve pressure gradient of 11.5±5.2 mmHg; mean effective orifice area was 1.7±0.4 cm2.

All cause mortality and disabling stroke were low at 30 days (4.2 percent and 1.7 percent, respectively). Additional clinical event rates were consistent with those reported for other valves. Aortic regurgitation at 30 days was negligible in 99 percent of patients (78.3 percent none, 5.2 percent trace and 15.5 percent mild). The total stroke rate, disabling and non-disabling, was 5.9 percent, which is the same as the rate as the Edward’s Sapien valve’s performance in the PARTNER trial.

“These findings suggest this valve, which is a differentiated, second generation TAVR device, will be a valuable addition for the treatment of severe aortic stenosis,” said Ian Meredith, MBBS, Ph.D., director, Monash HEART, executive director, Monash Cardiovascular Research Centre, professor of medicine, Monash University in Melbourne, Australia, and lead investigator of the study.

For more information: http://www.crf.org, http://www.bostonscientific.com

MORE LIKE THIS

SOURCE

http://www.dicardiology.com/article/second-generation-transcatheter-aortic-valve-shown-successfully-address-tavr-complications?goback=%2Egde_675087_member_5803962928159797249#%21

“This is the first time the societies have ever filed for an investigational device exemption,” former ACC president Ralph Brindis is quoted as saying. “The goal of the effort is to gain reimbursement for an expanded set of procedures with Sapien to make the device accessible to more patients.”

Two medical societies jump into clinical trial effort for TAVR tech – FierceMedicalDevices http://www.fiercemedicaldevices.com/story/two-medical-societies-jump-clinical-trial-effort-tavr-tech/2013-02-12#ixzz2Kjk7MHEi

The new trials will mean that reimbursement will now be possible for some of these uses when patients are enrolled in the clinical trials. According to Mack, the NCD “took off-label use off the table. If you are a cynic this is good, but if you’re a practitioner this is tying your hands.”

http://www.forbes.com/sites/larryhusten/2013/02/12/two-medical-societies-break-new-ground-to-test-medical-device/

According to Forbes, STS president Michael Mack told The Gray Sheet (a subscription-only publication) that the first trial will look at alternatives to transfemoral approaches in 1,000 patients who couldn’t otherwise have aortic valve surgery. There was a coordinated effort to develop a trial protocol, worked out between the CACC, STS, CMS, Edwards and the FDA. Expanded uses require an FDA label, he noted, and the only way to do that is to conduct a clinical trial with an IDE in hand.

So why would expanded TAVR uses be necessary? Well, the procedure has become very much in demand, and physicians already began pursuing off-label uses once they learned the initial TAVR procedure, Brindis told Forbes. The magazine notes that the entrance of both the STS and ACC into TAVR clinical trials greatly expands the TVT registry that they run, which tracks TAVR use in the United States to help physicians comply with Medicare’s National Coverage Decision for TAVR.

TAVR is indeed a hot space. St. Jude Medical ($STJ) won a CE mark for its Portico transcatheter heart valve late last fall, and Edwards’ Sapien competes with Medtronic‘s ($MDT) CoreValve in Europe. And smaller companies such as Micro Interventional Devices are working hard to develop surgical tools designed to enable TAVR procedures.

Brindis and Mack said that the ACC and STS worked closely with CMS,the FDA, and Edwards to develop the trial protocol. In the trial, patients not eligible for aortic valve surgery will receive TAVR through transapical and transaortic approaches and will be compared with the results of patients in the original PARTNER A trial who received TAVR through the transapical approach. Mack concedes that the trial design is not idea. “There is no perfect comparator,” he acknowledged.

http://www.forbes.com/sites/larryhusten/2013/02/12/two-medical-societies-break-new-ground-to-test-medical-device/

Other experts in the field contacted by CardioBrief agreed that the challenges of trial design in this situation are quite formidable. Randomized trials are not always feasible and, in some situations, may be unethical. The IDE is an attempt to balance the need for rational clinical trials, on the one hand, and the growing pressure to perform off-label procedures. It should be noted that an important safeguard for patients remains in place: all potential TAVR patients will still need to be evaluated by both a cardiologist and a cardiac surgeon as part of the “heart team” approach mandated by the FDA and the NCD.

http://www.forbes.com/sites/larryhusten/2013/02/12/two-medical-societies-break-new-ground-to-test-medical-device/

The ACC and STS are now working to gain FDA approval to perform two more studies. One would examine the role of alternative approaches in the high-risk population eligible for surgery. The second would study valve-in-valve TAVR procedures. Both studies also present challenging problems of trial design. Mack said he anticipates FDA approval of these protocols in the next few months.

Edwards agreed in principle to fund the clinical trials. An Edwards representative confirmed that the company planned to support these new trials, but the details have not yet been hammered out.

Mack states that the power and scope of the TVT registry actually makes it easier for ACC and STS to move forward than Edwards. Further, Mack believes that some indications are like “orphan” indications that are medically but not commercially compelling.

http://www.forbes.com/sites/larryhusten/2013/02/12/two-medical-societies-break-new-ground-to-test-medical-device/

Larry Husten, wrote on 5/04/2012 in Forbes, The final decision earlier this week by the Centers for Medicare & Medicaid Services (CMS) to provide reimbursement for TAVR was the latest step in a long, ongoing process that, for once, didn’t appear broken, and, in fact, represented an unusual consensus among physicians, regulators, insurers, and other involved parties In his article

Politics and Transcatheter Aortic Valve Replacement

From the first early stages of its development, the prospect of transcatheter aortic valve replacement (TAVR) provoked two broad and competing fears:

Regulatory safeguards would kill a promising new technology, denying its life-saving benefits to many thousands of desperately sick people.
The stampede to stake a claim in a promising, highly lucrative new territory would lead to the exploitation and mistreatment of many thousands of desperately sick people.

http://www.forbes.com/sites/larryhusten/2012/05/04/politics-and-transcatheter-aortic-valve-replacement/

Scott Gottlieb, a conservative activist who is a former FDA deputy commissioner and CMS adviser, concludes that the CMS ruling means “that for costly procedures, Washington will be making more of these choices for us.” In a posting on the American Enterprise Institute’s The Enterprise Blog, Gottlieb writes that the decision “is a vivid example of how our healthcare is going to get reimbursed now that Washington calls more of the shots.”

http://www.forbes.com/sites/larryhusten/2012/05/04/politics-and-transcatheter-aortic-valve-replacement/

CMS has insisted that doctors who perform the procedure have adequate training and that the hospitals where the procedures are performed have sufficient experience and adequate facilities. Perhaps Scott Gottlieb, MD would be happy to send an elderly relative for TAVR to a local community hospital with little experience in the procedure. It was precisely to avoid this scenario that the American College of Cardiology and the Society of Thoracic Surgeons supported CMS in this coverage decision. I fail to see how anyone would benefit by widespread proliferation of TAVR by novice operators at inexperienced centers.

Physicians,
Regulators,
Insurers,
CMS,
Medical Device Manufactures
ACC, and
STS

will be cooperating in the College of Cardiology and Society of Thoracic Surgeons newly announced involvement in Clinical Trials on broader use of transcatheter aortic valve replacement (TAVR) procedure to include new patients that this procedure will be indicated for and CMS reimbursed.

Other aspects of the Procedure, and the role EdwardsSciences played in the development and the Industry Leadership it holds in the US, are covered in several articles on this Open Access Online Scientific Journal, including the following:

August 7, 2012 – Transcatheter Aortic Valve Implantation (TAVI): risk for stroke and suitability for surgery

http://pharmaceuticalintelligence.com/2012/08/07/transcatheter-aortic-valve-implantation-tavi-risky-and-costly-2/

August 2, 2012 – Transcatheter Aortic Valve Implantation (TAVI): Risky and Costly

http://pharmaceuticalintelligence.com/2012/08/02/transcatheter-aortic-valve-implantation-tavi-risky-and-costly/

June 4, 2012 – Investigational Devices: Edwards Sapien Transcatheter Aortic Valve Transapical Deployment http://pharmaceuticalintelligence.com/2012/06/04/investigational-devices-edwards-sapien-transcatheter-heart-valve/

June 10, 2012 — Investigational Devices: Edwards Sapien Transcatheter Aortic Heart Valve Replacement Transfemoral Deployment http://pharmaceuticalintelligence.com/2012/06/10/investigational-devices-edwards-sapien-transcatheter-aortic-heart-valve-replacement-transfemoral-deployment/

June 19, 2012 — The Centers for Medicare & Medicaid Services (CMS) covers transcatheter aortic valve replacement (TAVR) under Coverage with Evidence Development (CED) http://pharmaceuticalintelligence.com/2012/06/19/the-centers-for-medicare-medicaid-services-cms-covers-transcatheter-aortic-valve-replacement-tavr-under-coverage-with-evidence-development-ced/

1/29/2013 — Direct Flow Medical Wins European Clearance for Catheter Delivered Aortic Valve

http://pharmaceuticalintelligence.com/2013/01/29/direct-flow-medical-wins-european-clearance-for-catheter-delivered-aortic-valve/

6/19/2012 Executive Compensation and Comparator Group Definition in the Cardiac and Vascular Medical Devices Sector: A Bright Future for Edwards Lifesciences Corporation in the Transcatheter Heart Valve Replacement Market

http://pharmaceuticalintelligence.com/2012/06/19/executive-compensation-and-comparator-group-definition-in-the-cardiac-and-vascular-medical-devices-sector-a-bright-future-for-edwards-lifesciences-corporation-in-the-transcatheter-heart-valve-replace/

Posted in Aortic Valve: TAVR, TAVI vs Open Heart Surgery, Bio Instrumentation in Experimental Life Sciences Research, Cardiac & Vascular Repair Tools Subsegment, Ecosystems & Industrial Concentration in the Medical Device Sector, FDA Regulatory Affairs, Frontiers in Cardiology and Cardiovascular Disorders, Health Economics and Outcomes Research, Health Law & Patient Safety, Interviews with Scientific Leaders, Medical Devices R&D and Inventions, Medical Devices R&D Investment, Regulated Clinical Trials: Design, Methods, Components and IRB related issues, Valves & Tools | Tagged ACC, Clinical trial, Edwards, FDA, Food and Drug Administration, Medtronic, St. Jude Medical, STS | 6 Comments

6 Responses

on February 13, 2013 at 7:22 PM | Reply Introducing Western Medical Devices in China « Pharmaceutical Intelligence

PUT IT IN CONTEXT OF CANCER CELL MOVEMENT

The contraction of skeletal muscle is triggered by nerve impulses, which stimulate the release of Ca2+ from the sarcoplasmic reticuluma specialized network of internal membranes, similar to the endoplasmic reticulum, that stores high concentrations of Ca2+ ions. The release of Ca2+ from the sarcoplasmic reticulum increases the concentration of Ca2+ in the cytosol from approximately 10-7 to 10-5 M. The increased Ca2+ concentration signals muscle contraction via the action of two accessory proteins bound to the actin filaments: tropomyosin and troponin (Figure 11.25). Tropomyosin is a fibrous protein that binds lengthwise along the groove of actin filaments. In striated muscle, each tropomyosin molecule is bound to troponin, which is a complex of three polypeptides: troponin C (Ca2+-binding), troponin I (inhibitory), and troponin T (tropomyosin-binding). When the concentration of Ca2+ is low, the complex of the troponins with tropomyosin blocks the interaction of actin and myosin, so the muscle does not contract. At high concentrations, Ca2+ binding to troponin C shifts the position of the complex, relieving this inhibition and allowing contraction to proceed.

Figure 11.25

Association of tropomyosin and troponins with actin filaments. (A) Tropomyosin binds lengthwise along actin filaments and, in striated muscle, is associated with a complex of three troponins: troponin I (TnI), troponin C (TnC), and troponin T (TnT). In (more) Contractile Assemblies of Actin and Myosin in Nonmuscle Cells

Contractile assemblies of actin and myosin, resembling small-scale versions of muscle fibers, are present also in nonmuscle cells. As in muscle, the actin filaments in these contractile assemblies are interdigitated with bipolar filaments of myosin II, consisting of 15 to 20 myosin II molecules, which produce contraction by sliding the actin filaments relative to one another (Figure 11.26). The actin filaments in contractile bundles in nonmuscle cells are also associated with tropomyosin, which facilitates their interaction with myosin II, probably by competing with filamin for binding sites on actin.

Figure 11.26

Contractile assemblies in nonmuscle cells. Bipolar filaments of myosin II produce contraction by sliding actin filaments in opposite directions. Two examples of contractile assemblies in nonmuscle cells, stress fibers and adhesion belts, were discussed earlier with respect to attachment of the actin cytoskeleton to regions of cell-substrate and cell-cell contacts (see Figures 11.13 and 11.14). The contraction of stress fibers produces tension across the cell, allowing the cell to pull on a substrate (e.g., the extracellular matrix) to which it is anchored. The contraction of adhesion belts alters the shape of epithelial cell sheets: a process that is particularly important during embryonic development, when sheets of epithelial cells fold into structures such as tubes.

The most dramatic example of actin-myosin contraction in nonmuscle cells, however, is provided by cytokinesisthe division of a cell into two following mitosis (Figure 11.27). Toward the end of mitosis in animal cells, a contractile ring consisting of actin filaments and myosin II assembles just underneath the plasma membrane. Its contraction pulls the plasma membrane progressively inward, constricting the center of the cell and pinching it in two. Interestingly, the thickness of the contractile ring remains constant as it contracts, implying that actin filaments disassemble as contraction proceeds. The ring then disperses completely following cell division.

Figure 11.27

Cytokinesis. Following completion of mitosis (nuclear division), a contractile ring consisting of actin filaments and myosin II divides the cell in two.

http://www.ncbi.nlm.nih.gov/books/NBK9961/

This is good. I don’t recall seeing it in the original comment. I am very aware of the actin myosin troponin connection in heart and in skeletal muscle, and I did know about the nonmuscle work. I won’t deal with it now, and I have been working with Aviral now online for 2 hours.

I have had a considerable background from way back in atomic orbital theory, physical chemistry, organic chemistry, and the equilibrium necessary for cations and anions. Despite the calcium role in contraction, I would not discount hypomagnesemia in having a disease role because of the intracellular-extracellular connection. The description you pasted reminds me also of a lecture given a few years ago by the Nobel Laureate that year on the mechanism of cell division.

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on March 21, 2013 at 1:02 PM | Reply Minimally Invasive Structural CVD Repairs: FDA grants 510(k) to Philips’ EchoNavigator – X-ray and 3-D Ultrasound Image Fused. | Pharmaceutical Intelligence

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on June 17, 2013 at 11:42 AM | Reply Transcatheter Aortic Valve Replacement (TAVR): Postdilatation to Reduce Paravalvular Regurgitation During TAVR with a Balloon-expandable Valve | Pharmaceutical Intelligence

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on June 17, 2013 at 4:04 PM | Reply Trans-apical Transcatheter Aortic Valve Replacement in a Patient with Severe and Complex Left Main Arterial (LMA) Disease | Pharmaceutical Intelligence

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