Clinical Trial and Research News

December 6, 2010 — The CRYSTAL AF trial will enroll approximately 450 people who have been diagnosed with a cryptogenic stroke across 55 centers. Approximately half will be continuously monitored by an FDA-approved implanted cardiac monitor, which will monitor for the first documented event of atrial fibrillation following enrollment in the trial. Co-investigators Rod Passman, MD and Richard Bernstein, MD are on the international steering committee for the CRYSTAL AF trial sponsored by Medtronic Cardiac Rhythm Disease Management. Researchers are currently seeking additional subjects for enrollment in the CRYSTAL AF trial. To learn more about the study, visit www.nmh.org/nm/crystal+af+trial or call +1 (312) 695-3264.

Catheter Ablation versus Antiarrhythmic Drug Therapy for Atrial Fibrillation Trial (CABANA) — www.cabanatrial.org
The investigator-initiated CABANA Trial is designed to test the hypothesis that the treatment strategy of percutaneous left atrial catheter ablation for the purpose of the elimination of atrial fibrillation (AF) is superior to current state-of-the-art therapy with either rate control or anti-arrhythmic drugs for reducing total mortality (primary endpoint) and decreasing the composite endpoint of total mortality, disabling stroke, serious bleeding and cardiac arrest (secondary endpoint) in patients with untreated or incompletely treated AF warranting therapy. This 125 center mortality study will randomize 3,000 pts over three years to a strategy of catheter ablation (n=1500) vs. state-of-the-art rate or rhythm control drug therapy (n=1500). The CABANA trial will disclose the role of medical and non-pharmacologic therapies for an ever-escalating national healthcare dilemma establish the cost and impact of therapy on quality of life and will help determine if AF is a modifiable risk factor for increased mortality.

Boston Scientific CRT-Ds Expanded Indication Based on MADIT-CRT Trial — The FDA has approved an expanded indication exclusive to Boston Scientific CRT-Ds to include high-risk*, NYHA Class I (ischemic) & II (ischemic or non-ischemic) heart failure patients with left bundle branch block (LBBB). Early CRT-D intervention enables physicians to reduce death and heart failure events in patients’ earliest phase of heart failure — regardless of the presence of symptoms. This expanded indication is based on updated results from the landmark MADIT-CRT trial. MADIT-CRT is the first study to prove that in high-risk, NYHA Class I & II patients with LBBB, early CRT-D intervention reduces the relative risk of all-cause mortality or first heart failure event by 57% compared to ICD therapy. (p < 0.001).** Results were driven by a 35% relative reduction in the risk of all-cause mortality (p = 0.048) and a 63% relative reduction in the risk of first heart failure event (p < 0.001). Full results of the MADIT-CRT trial can be reviewed at www.madit-crt.com.
* High-risk is defined as ejection fraction < 30%, QRS width > 130 ms and left bundle branch block. NYHA Class I is ischemic only.
**Left bundle branch block (LBBB) was not an inclusion parameter for the MADIT-CRT trial. However, a significant interaction between treatment and bundle branch block morphology was detected. Further analyses revealed that LBBB is an objective discriminator of patient benefit from CRT-D regardless of other baseline characteristics. The subgroup of MADIT-CRT patients without LBBB did not show statistically significant benefit in the primary and secondary endpoints.

SAFARI Registry Seeks to Clear Path in AF Jungle — The FDA has initiated the Safety of Atrial Fibrillation Ablation Registry Initiative (SAFARI), spearheaded by the Cardiac Safety Research Consortium, which will help define clinical practice of long-term persistent atrial fibrillation ablation and collect outcomes and key performance indicators.

Hospital Studies Irregular Heartbeats — Hartford Hospital is recruiting patients with atrial fibrillation (AF) to participate in the CABANA Trial to determine whether catheter ablation is more effective than state-of-the-art drug therapy in managing AF symptoms and reducing mortality.

Multicenter Automatic Defibrillator Implantation Trial-CRT (MADIT-CRT) — According to a sub-study of the MADIT-CRT, left ventricular (LV) leads positioned in the apical region when compared to the mid-ventricular or basal regions are associated with a significantly increased risk of heart failure (HF) and death in patients receiving cardiac resynchronization therapy (CRT). This is the first trial to evaluate clinical outcomes based on the LV lead position within a mildly symptomatic CRT patient population. In MADIT-CRT, patients were randomly assigned to receive CRT-D or implantable cardioverter defibrillators (ICD) therapy. A total of 1,820 patients were enrolled in 110 centers and a significant portion of the patient population was women (25 percent). The results of the MADIT-CRT study showed that over a two-year follow up period, CRT-D was associated with a 34 percent overall reduction of death and HF in minimally symptomatic patients, and that CRT-D was more effective in women than men.

St. Jude Medical Wins FDA Nod For RF Ablation Trial — Device maker St. Jude Medical Inc. received an Investigational Device Exemption from the U.S. Food and Drug Administration to begin enrollment in the IRASE AF (IRrigated Ablation System Evaluation for AF) trial, a multicenter, randomized, single-blind study evaluating the safety and efficacy of the company's Duo 12 port open irrigated catheter ablation system for treatment of atrial fibrillation. The trial is expected to last three years, involve 324 patients, and take place in both U.S. and international markets. It will involve patients afflicted with paroxysymal atrial fibrillation, a type of irregular heartbeat that begins suddenly and ends spontaneously. Patients will be treated with a noninvasive procedure known as ablation, which refers to the removal of tissue via erosion or vaporization.

Journal of American College Of Cardiology Publishes Study Demonstrating Safety & Effectiveness Of Laser Assisted Lead Remova l— Spectranetics Corporation announced publication of the four-year, retrospective LExICon (Lead Extraction in Contemporary Settings) study in the February 9, 2010 issue of the Journal of American College of Cardiology. The study evaluated the safety and efficacy of laser assisted lead removal using the Spectranetics laser sheath (SLS® II). The LExICon study, an observational, multicenter, retrospective study, was designed to examine the safety and effectiveness of laser assisted lead removal and the indications, outcomes, and risk factors in a large series of consecutive patients. The study further sought to determine clinical and procedural success and complication types, and identify relationships between complication factors including duration of implant, lead type, lead position, center experience, age and gender. LExICon evaluated the removal of 2,405 leads in 1,449 patients at 13 centers experienced in lead extraction from the United States and Canada between January 2004 and December 2007.

Cardio3 BioSciences Completes Patient Enrollment In First Stage Of Pivotal Trial Of C-Cure® In Heart Failure — Cardio3 BioSciences announced that it has completed enrollment in the first stage of its pivotal Phase II/III trial of C-Cure, a unique stem cell therapy for heart failure. Forty-five patients have now enrolled in the study, which is being conducted at centres in Belgium and Serbia.

Cardiome Announces Investigational Candidate, Vernakalant, Meets Primary Endpoint in European Comparator Study — Cardiome Pharma Corp. announced that the recently-completed Phase 3 European Comparator Study (the AVRO study) evaluating vernakalant (iv) versus amiodarone for the acute conversion of atrial fibrillation met its primary endpoint.

nContact Surgical, Inc. Announces Initiation Of Clinical Trials For The Treatment Of Paroxysmal Atrial Fibrillation — nContact Surgical, Inc. announces the initiation of a feasibility clinical trial designed to evaluate the safety and efficacy of a combined surgical and catheter procedure, the convergent procedure, for the treatment of symptomatic paroxysmal atrial fibrillation.

Sorin Group Announces The First Inclusion In The Clepsydra Clinical Study In the US — Sorin Group announces the first inclusion of a patient in the Clepsydra clinical trial. The study will investigate the sensitivity to changes in heart failure status of PhD(TM), a diagnostic feature available in the Paradym(TM) family of ICDs in Europe and under clinical evaluation in Implantable cardiac resynchronization therapy defibrillators in Europe and the US.

Society Attends FDA Gender Device Trials Seminar (01/07/09) — In December, the Society’s Health Policy staff attended the Gender Device Trials Seminar, held at the Food and Drug Administration White Oaks Conference Center. This seminar, a joint collaboration between the FDA’s Office of Women’s Health and AdvaMed’s medical technology learning institute, explored public policy and industry’s concerns regarding the study and analysis of sex differences in the clinical evaluation of cardiovascular medical devices. Learn more »

Society Volunteers Participate in FDA Workshop on Women in Device Clinical Trials (06/02/08) — On Monday, June 2, 2008, Sana Al-Khatib MD, FHRS and Mina Chung MD, FHRS served as panelists on behalf of the Heart Rhythm Society at a workshop sponsored by the U.S. Food & Drug Administration (FDA) Office of Women's Health and the Center for Devices and Radiological Health. "Exploration of Public Policy Development Regarding the Study and Analysis of Sex Differences in the Clinical Evaluation of Cardiovascular Medical Products" focused on strategies for improving the proportion of women in CV trials and developing recommendations for the analysis and reporting of safety and effectiveness by sex. Learn more »

PREFER Trial — A new study finds that physicians can detect and diagnose clinically actionable events earlier in pacemaker patients who utilize remote interrogation compared to those that are followed via routine office visits augmented by transtelephonic monitoring (TTM). These results are part of the PREFER Trial, the first to compare remote monitoring diagnosis rates to diagnosis rates using traditional pacemaker follow-up. The prospective, randomized trial analyzed data from 897 patients from 50 centers throughout the United States. At enrollment, patients were randomized 2:1 to have pacemaker follow-up by a combination of in-person programming evaluations augmented by either remote interrogation or transtelephonic rhythm strip evaluations. At each follow-up visit or scheduled transmission, physicians reviewed the available data for pre-specified clinically actionable events.

Optimizing Cardiovascular Device Thromboresistance for Eliminating Anticoagulants — On November 4, 2010 a five-year, $7.5 million grant from the National Institutes of Health (NIH) was awarded. The Phase II Quantum Grant, provided by the National Institute of Biomedical Imaging and Engineering (NIBIB), a division of the NIH, will be used to optimize the design of cardiovascular devices. In Phase I a Device Thrombogenicity Emulator (DTE) was developed, which measures the potential for blood clotting in cardiovascular devices by mimicking the conditions in the device. During Phase II, SynCardia will use the DTE to tweak the geometry of the devices to optimize the design and minimize or eliminate ‘hot spot’ trajectories where clots can form. The ultimate goal is to eliminate the need for anticoagulation in patients supported by these devices. Danny Bluestein, Ph.D., Principal Investigator and Professor of Biomedical Engineering at Stony Brook University is working with several companies to test and optimize the designs of various cardiovascular devices including prosthetic heart valves, left ventricular assist devices (LVADs), biventricular assist devices (BiVADs) and the SynCardia temporary Total Artificial Heart. Collaborators include four industrial partners: SynCardia Systems, Inc., MicroMed Cardiovascular, Innovia LLC and Medtronic-ATS Medical Inc. Each group will receive a sub-award of the grant for their contributions to the project.

Heart Devices Underused —Since 1980, when a physician at Johns Hopkins Hospital first implanted a defibrillator in a human being, doctors have found that the devices can halt sudden cardiac death in many patients whose hearts have weakened pumping ability, as well as for some who have suffered a heart attack. But a February 19, 2010 study by researchers at the University of Maryland Medical Center shows that about half of all patients who meet nationally accepted guidelines for treatment with implantable cardioverter-defibrillators, known as ICDs, are not receiving the recommended treatment. Based on records from 167 cardiology practices across the United States, the study also found that older patients, African-Americans and those without health insurance were less likely than other patients to receive the devices. Heart failure patients treated outside the northeastern U.S. were less likely to be treated in accordance with the guidelines.

Common Gene Variant May Increase Risk For A Type Of Cardiac Arrhythmia — An international research team has identified a common gene variant associated with a form of the irregular heartbeat called atrial fibrillation. In their report in the journal Nature Genetics, published online in February, the investigators describe finding that variations affecting a protein that may help control the heart's electrical activity appear to increase the risk of what is called lone atrial fibrillation (AF), a type seen in younger individuals with no other form of heart disease.

In Long QT Syndrome, Syncope During Beta-Blockade An Indication For ICD Therapy — According to a new study published in the Journal of American College of Cardiology, an implantable cardioverter defibrillator should be considered when patients with long QT syndrome have syncope while on beta-blockers. Researchers found a higher risk for fatal arrhythmias in this population, especially before puberty and in females.

Predictors Of Atrial Fibrillation Progression Identified — Study finds that a substantial percentage of patients with paroxysmal atrial fibrillation progress to sustained AF within a year, which may be predicted by five factors known to affect atrial structural remodeling: hypertension, age (older than 75 years), prior transient ischemic attack or stroke, chronic obstructive pulmonary disease, and heart failure.

Researchers Gain Detailed Insight Into Failing Heart Cells Using New Nano Technique — Researchers have been able to see how heart failure affects the surface of an individual heart muscle cell in minute detail, using a new nanoscale scanning technique. The findings may lead to better design of beta-blockers and improvements in current therapeutic approaches to treating heart failure and abnormal heart rhythms.

Dabigatran Reduces Risk Of Stroke And Embolism In Patients With AF — Journal of the American Academy of Physician Assistants , December 14, 2009 — Clinical question: Is dabigatran safer and more effective than warfarin for the prevention of complications of atrial fibrillation (AF)? Dabigatran was slightly more effective than warfarin at preventing stroke and embolism, especially the dosage of 150 mg given twice a day, and may reduce all-cause mortality (number needed to treat [NNT] = 200 over 2 years). It will be important to balance efficacy with the higher cost but greater convenience of dabigatran when comparing it with standard warfarin therapy. (Level of evidence = 1b)

Speeding Development Of Drug Treatments For Heart Failure With University of Minnesota Invention (Medical News Today, November 25, 2009) — Research conducted by University of Minnesota scientists, in collaboration with Celladon Corporation, has led to the invention of technology to more rapidly identify compounds for the treatment of heart failure. The technology, developed by the universitys David Thomas and Razvan Cornea and Celladon Corporations Krisztina Zsebo, allows for increased screening efficiency of compounds capable of disrupting the interactions of proteins implicated in the development of heart failure. Fluorescence resonance energy transfer (FRET) is used to measure disruption of the calcium regulatory system, which has long been implicated in cardiovascular disease. This will provide key information on a particular drugs likelihood of success early in the screening process, since compounds that decrease FRET are good candidates for further development.

Innovative Imaging System To Study Sudden Cardiac Arrest Developed (ScienceDaily, November 1, 2009) — A research team at Vanderbilt University has developed an innovative optical system to simultaneously image electrical activity and metabolic properties in the same region of a heart, to study the complex mechanisms that lead to sudden cardiac arrest. Tested in animal models, the system could dramatically advance scientists' understanding of the relationship between metabolic disorders and heart rhythm disturbances in humans that can lead to cardiac arrest and death, and provide a platform for testing new treatments to prevent or stop potentially fatal irregular heartbeats, known as arrhythmias. The 11-year-old research project would have been terminated this year due to lack of funding, but a $566,000 American Recovery and Reinvestment Act grant from the NHLBI is enabling the 13-member research team to continue developing and testing the innovative optical system.

ICD/CRT Use In HF Varies Widely, Most Eligible Patients Missing Out: US And European Surveys — An analysis from the Registry to Improve the Use of Evidence-Based Heart Failure Therapies in the Outpatient Setting (IMPROVE HF) found whether by region in the US or by country in Europe, there is wide variation in the likelihood that an eligible patient with heart failure will receive a biventricular pacemaker for resynchronization, an implantable defibrillator, or a device that combines the two.