Posts Tagged ‘clinical trials’

Legacy of Innovation Continues at Emory with Successful Arrhythmia Clinical Trial

The device is weighs less than a small coin and is only a little longer than a U.S. nickel. Image credit: Medtronic

The device is weighs less than a small coin and is only a little longer than a U.S. nickel. Image credit: Medtronic

Last week, a clinical trial that Emory researchers participated in was presented at the 2015 American Heart Association Scientific Sessions. The presentation revealed that the world’s smallest, minimally invasive cardiac pacemaker — the Micra Transcatheter Pacing System (TPS) — was successfully implanted in nearly all of the patients participating in the international clinical trial. The study was also published in The New England Journal of Medicine.

The non-randomized clinical trial enrolled a total of 725 patients across 56 centers, including Emory. Results showed the Micra TPS, which is about the size of a large vitamin and weighs less than a small coin, was successfully implanted in 99.2 percent of all patients (719 of 725). The device also over exceeded its safety and effectiveness measures and approximately 96 percent of patients experienced no major complications, which is 51 percent fewer than the complication rate seen in patients with conventional pacing systems.

Emory Healthcare cardiologists were the first in Georgia, and among the first in the United States, to begin implanting the Micra TPS last year. Emory was the top enrolling U.S. site in the trial.

“We were pleased to participate in this important trial, as this will likely be the way pacemakers are implanted in the future,” says Emory site principle investigator Michael S. Lloyd, MD, associate professor of medicine, Emory University School of Medicine.

“The outstanding results are very encouraging and will allow us to continue to offer this novel device as a safe alternative to our patients.”

Dr. Lloyd, a cardiac electrophysiologist, implanted the first Micra TPS at Emory in April 2014 at Emory University Hospital. He says there are an estimated 3 million people living with pacemakers, and about 600,000 pacemakers are implanted in the world every year.

During the procedure, the tiny device — approximately one-tenth the size of a conventional pacemaker — is delivered through a catheter inserted in the femoral vein to the inside of the heart. Once positioned, it securely attaches to the endocardial tissue of the heart wall and sends electrical pulses to the heart through electrode tips whenever it senses an abnormal heart rhythm.

Unlike conventional pacemakers, the Micra TPS does not require the use of wires, known as “leads.” These leads, threaded through blood vessels to connect to the heart, are sometimes the source of serious medical complications such as infection and vein injury.

Another important difference between the new device and traditional pacemakers is that implantation of the Micra TPS does not require a surgical incision and the creation of a “pocket” under the skin. Conventional pacemakers require a more invasive surgery.

“By not creating a pocket and implanting a rigid device directly below the skin, it eliminates another potential source of complications and any visible sign of the device,” says cardiologist Mikhael El Chami, MD, associate professor of medicine, who is also implanting the Micra TPS device at Emory.

For more information on Micra TPS at Emory, please call 800-75-EMORY.

To see the full NEJM article, please click here. To view the original Emory News Center press release, click here.

About Emory’s Arrhythmia Treatment Program

Emory’s arrhythmia treatment program is one of the most comprehensive and innovative clinics for heart rhythm disorders in the country. Emory’s electrophysiologists have been pioneers in shaping arrhythmia treatment options for patients with arrhythmias, such as atrial fibrillation, as well as for those with congestive heart failure. As primary and principal investigators for many national clinical trials, Emory has participated in numerous atrial fibrillation (A-fib, AF) and atrial flutter (a-flutter) studies with multiple catheters and energy sources. We are the only center in Georgia participating in a trial that provides alternatives to blood thinners to prevent stroke in patients with A-fib. We also have ongoing clinical trials of new pacemakers, defibrillators, ablation catheters, as well as new ways to use existing devices to help patients.

Stem Cell Research Reveals Promising Data for Heart Attack Patients

Stem Cell Research for Heart PatientsDuring a heart attack, every minute counts, especially when the type of heart attack is a STEMI (ST segment elevation myocardial infarction). STEMI is the most fatal type of heart attack and is caused by a prolonged blockage of blood supply in the heart, which weakens or deadens the heart muscle.

In a recent clinical trial named PreSERVE AMI, research investigators from 60 different sites conducted one of the largest studies using bone marrow cell therapy for heart attack in the United States. The study treated 161 patients following a STEMI heart attack using their own bone marrow cells in hopes of improving their recovery process.

“For cardiologists, our key goal is to keep patients from progressing to worsening heart muscle function and death after a major heart attack,” said Dr. Arshed A. Quyyumi, professor of medicine at Emory University School of Medicine, co-director of the Emory Clinical Cardiovascular Research Institute and lead principal investigator of the PreSERVE AMI study. Heart attack patients are usually at high risk of downstream adverse events, including chronic heart failure, recurrent heart attack, significant arrhythmias, premature death or acute coronary syndrome.

About the PreSERVE AMI Clinical Trial

The PreSERVE AMI study, sponsored by NeoStem, Inc., produced promising results that will allow stem cell researchers to continue making progress in determining the cell type and dose that benefit patients. After receiving the standard of care following a heart attack, which is stenting, participating patients were enrolled if their ejection fraction, a measure of the heart’s pumping capacity and indicator of the severity of the attack, was less than 48 percent.

After trial enrollment, patients had bone marrow cells extracted, sorted and then re-injected into the heart. Bone marrow contains rare cells which are believed to promote healing and recovery of blood flow. In this study, extracted bone marrow cells were shipped to NeoStem’s facility where sophisticated stem cell technology sorted and selected the rare cells called CD34+ cells before they were returned for re-injection into the patient.

The stem cell study was randomized and not all patients received the same dose of cells — some received the minimum of 10 million cells while others received up to 40 million — and a half of participants received placebo.

Discovery and Results of the PreSERVE AMI Clinical Trial

Recovery and outcomes of PreSERVE AMI were assessed in several ways: MACE (major adverse cardiac events, ranging from hospitalization for chest pain to death), ejection fraction and blood flow in the heart. Cardiac imaging was performed six months after treatment and MACE reported from an average of twelve months of follow-up.

Highlights of initial trial results include:

  • A statistically significant mortality benefit in patients treated with CD34+ as compared to the placebo group. Mortality was 3.6 percent in the control group, and zero in the treatment group.
  • A statistically significant dose-dependent reduction in serious adverse events.
  • MACE occurred in 14% of control participants, in 17% of subjects of who received less than 14 million CD34+ cells, in 10% of subjects who received greater than 14 million CD34+ cells, and in 7% of subjects who received greater than 20 million CD34+ cells. Therefore, it appears that the numerical decrease in MACE is dependent on cell dose size.
  • Patients treated with a dose of greater than 20 million CD34+ cells were seen to have a statistically significant improvement in their ejection fraction compared to the placebo group.
  • No significant effects on improvement in blood flow, measured by SPECT imaging, between the treatment and the control group based on 6 months of data.**

According to Dr. Quyyumi, the U.S. Food and Drug Administration (FDA) officials have told stem cell researchers using cell therapy that MACE (clinical outcomes) are the important measure of success and SPECT imaging is not, although imaging provides insightful information on the heart and therapy being issued.

Summary of PreSERVE AMI phase II Clinical Trial

In the treatment group that received the largest dose of CD34+ cells, the MACE rate was half that of control group, which is a good indicator that cell dose impacts MACE outcomes. But comparing that measure to the placebo group (versus the entire treatment group), bone marrow cell therapy did not have a significant effect on MACE.

One positive, NeoStem has reported that because of this phase II trial, they are now able to standardize their procedures so that in the future, every patient should be able to receive 20 million CD34+ cells.

“It is encouraging to see clinically meaningful results this early in the study, and I look forward to future data readouts,” says Dr. Quyyumi. He is hopeful that additional follow-up trials should continue to make the effect of cell therapy treatment on clinical outcomes more clear.

“Research and discovery are important components to delivering exceptional patient care,” states Dr. Quyyumi. “Clinical trials are an iterative process that allows us to gain answers to the many questions we have about disease and treatment therapies, regardless of whether the clinical trial produces the outcome we want or expect.”

**Worthy to note, some patients who received cell therapy treatment had delays in getting stents (average 931 vs. 569 minutes), which puts the treated group at a disadvantage in terms of the heart’s recovery. This happened by chance resulting from the randomization of participants to placebo vs. treatment and not because of the treatment process since all bone marrow-related treatment procedures occurred after stenting.

About Emory Heart & Vascular Center

The Emory Heart & Vascular Center is comprised of four major areas of cardiovascular care– cardiology, vascular surgery, cardiothoracic surgery, and cardiac imaging. Each area is committed to providing superior cardiac and vascular patient care, promoting overall heart health, pioneering innovative clinical cardiovascular research, and training the best heart specialists and cardiologists in the world.

About Arshed Quyyumi, MD

Arshed Quyymi, MDDr. Arshed A. Quyyumi has been involved in clinical translational research in cardiovascular diseases for over 30 years. Dr. Quyyumi received his undergraduate degree in Pharmacology and medical degree from the University of London, England. He completed his residency at Guy’s and Royal Free Hospitals in London, and cardiology fellowships at National Heart Hospital, London; Massachusetts General Hospital, Boston; and the National Institutes of Health. After completion of his residency and fellowship, he served in several capacities in the Cardiology Branch of National Heart Lung and Blood Institute, NIH in Bethesda, MD, including Senior Investigator and Director of the Cardiac Catheterization Laboratory. In 2001 he was appointed Professor of Medicine in the Division of Cardiology at Emory University School of Medicine, and in 2010 he was named Co-Director of the Emory Clinical Cardiovascular Research Institute (ECCRI). Since 2005, Dr. Quyyumi has been awarded more than $9 million in research funding. He serves on the Editorial Boards of several national journals, is a member on several Scientific Advisory Boards, and is a reviewer for the NIH-NHLBI Study Sections. Dr. Quyyumi has authored more than 250 peer-reviewed publications and has been an invited speaker and session chair at numerous National and International scientific meetings and conferences.

Dr. Quyyumi’s research focus includes vascular biology, angiogenesis, progenitor cell biology, mechanisms of myocardial ischemia, the role of genetic and environmental risks on vascular disease, genomics, and metabolomics. Other interests have spanned the fields of personalized medicine and disparities in cardiovascular diseases. During his academic career, Dr. Quyyumi has carried out more than 50 NIH, industry-funded, or investigator-initiated projects, including numerous clinical trials. Dr. Quyyumi is a member of NeoStem’s advisory board. This relationship has been reviewed and approved by Emory University School of Medicine.

Related Resources

Emory Honored with International Heart Failure Research Grant!

Emory is one of 17 collaborating centers from 10 countries participating in a new international consortium project aimed at earlier detection and prevention of heart failure.

The European Commission has awarded a grant of almost $16 million (EUR 12 million) to the Heart Omics in Ageing (HOMAGE) project, with a goal of better identifying more specific biomarkers for heart failure and then developing methods for earlier detection of risk in the elderly population.

A biomarker, or biological marker, is a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention. It serves as a guide for health and physiology related assessments.

The prevalence of heart failure is increasing worldwide because of the aging population and a rising trend of risk factors for heart disease — such as diabetes, obesity and hypertension. Heart failure is a major cause of death and disability in the world and remains the most frequent cause of hospitalization for patients over 65 years old. An essential step in preventing heart failure is to first accurately identify individuals at high-risk.

Traditional risk factors such as high blood pressure still remain important clinical guides but we are now seeing more cases of heart failure develop in individuals who do not have any specific high risk diseases. Therefore, this research will try to determine more accurate methods of detecting heart failure risk using biomarkers leveraging the latest technology.

This project will evaluate data from 30,000 patients from 10 countries. Emory investigators will work with the National Institutes of Aging-funded Health Aging and Body Composition Study, to assess the value of this approach among 3,000 elderly individuals in the U.S.

HOMAGE will also lead a clinical trial to look for novel treatments of heart failure that can be targeted specifically to those patients at risk.

This research has the potential to benefit thousands of individuals in the U.S. and researchers at Emory are very excited to work with colleagues across Europe in this trans-Atlantic collaboration.

About Dr. Javed Butler
Professor of Medicine, Emory University School of Medicine
Director of Heart Failure Research at Emory

After completing medical school from Aga Khan University in Karachi, Pakistan, Dr. Butler did his residency and chief residency at Yale University, Masters in Public Health from Harvard University, and cardiology fellowship including transplant training at Vanderbilt University. Before moving to Emory University, he was the director for the Heart and Heart-Lung Transplant programs at Vanderbilt University. He also has done special cardiac imaging training at the Massachusetts General Hospital. He is on the Editorial Board for the Journal of the American College of Cardiology, Journal of Cardiac Failure, American Heart Journal and Congestive Heart Failure. He served on the American College of Cardiology Committee on Heart Failure and Transplantation. He is board certified in Cardiology, Internal Medicine, and Nuclear Cardiology. Currently he serves as the Deputy Chief Science Advisor for the American Heart Association. While also heavily involved in research and clinical care at Emory. Dr. Butler’s research focuses primarily on the disease progression, outcomes, and prognosis determination in patients with heart failure, with special emphasis on patients undergoing cardiac transplantation and left ventricular assist device placement. He has published many original research articles in multiple peer reviewed journals. He serves on the national board, events committee, and steering committees of several multicenter clinical trials. Dr. Butler is involved in the evaluation and management of all aspects of patients with heart failure including cardiac transplantation and left ventricular assist devices. He is also involved in the cardiac CT program at Emory University.

Related Resources

Transcatheter Valve Implantation Trial at Emory

The transcatheter heart valve is as large as 26 mm in diameter when expanded (left) and as small as 8 mm when collapsed over a balloon catheter (right).

In my last post, I focused on the definition, symptoms, diagnosis and treatment of aortic stenosis, a condition that can lead to heart failure. Sadly, aortic stenosis affects tens of thousands of Americans each year. In this post, I’d like to expand on one innovative treatment that is reducing the risks of this potentially fatal condition: transcatheter aortic valve implantation.

However, before we delve into an explanation of the treatment, let’s first review the specifics of the condition.

The aortic valve is the valve that connects the heart to the body, and is located between the left ventricle and the aorta. Blood flows through this valve, carrying oxygen to the rest of the body. There are typically three leaflets of tissue over the aortic valve that open and close and ensure proper blood flow. When the aortic valve becomes narrowed – either by degeneration or because is it abnormal from birth, the valve must be replaced to prevent heart failure.

Transcatheter aortic valve implantation is a new, innovative procedure used to replace the aortic valve. Rather than opening the chest and stopping the heart, we make a small incision in the groin or chest. We then insert a catheter (a thin, flexible tube) with a new aortic valve made of animal tissue through a blood vessel, using X-ray or ultrasound imaging to guide the device to the heart. As an alternative to open heart surgery, transcatheter aortic valve implantation has a substantially shorter recovery time and is particularly important for patients who are too weak to undergo the traditional process.

Emory has been involved in this groundbreaking technology since 2007, after Emory interventional cardiologist Vasilis Babaliaros, MD, helped bring the procedure back to us from France. The first cardiologist to perform transcatheter heart valve replacement was French doctor Alain Cribier, MD, who performed the procedure in 2002. Since 2007, we have completed approximately 85 transcatheter aortic valve implantations as part of a clinical trial, and we anticipate that the transcatheter valve will receive U.S. Food and Drug Administration (FDA) approval in late 2011. (You may view an animation video of the procedure here.)

Emory Heart & Vascular Center is proud to be one of the five largest centers in the United States and the most comprehensive in the Southeast to offer transcatheter aortic valve implantation. We are currently accepting patients for a new trial; for more information or to find out if you or someone you know may be a candidate for transcatheter aortic valve replacement, please contact me at 404-712-7667, or you may call Vinod Thourani, MD, at 404-686-2513. For other questions or comments on the procedure, I invite you to contribute in the comments section below.