RxPG News : Clinical Trials

Aspirin of no use in primary prevention of cardiovascular events- POPADAD trial

Sat, 01 Nov 2008 02:33:34 PST

( from http://www.rxpgnews.com ) In the BMJ this week, the results of the POPADAD (the prevention of progression of arterial disease and diabetes)trial were presented. Antiplatelet agents have been known to reduce the risk of secondary cardiovascular events in patients with diabetes and cardiovascular disease and even in peripheral vascular disease. This study was to look at whether antiplatelets would help in the primary prevention of cardiovascular events in patients with diabetes and asymptomatic peripheral vascular disease.
Around 1270 adults with type1 and type 2 diabetes mellitus and with ankle brachial pressure index of 0.99 or less were taken into the study. The participants had no symptomatic cardiovascular disease, aged above 40 years and were from 16 hospitals in Scotland. They were assigned to recieve one of the following- aspirin and placebo, antioxidant and placebo, aspirin and antioxidant, or double placebo.The primary end points were death from coronary artery disease or stroke, non fatal myocardial infarction or stroke and amputation due to critical limb ischemia.
There was no difference in the primary end points in the aspirin vs. non aspirin groups(18.2% vs 18.3%) and no difference between the placebo vs. non placebo group (18.3 vs. 18.2).
There have been previous trials which have shown that aspirin is of no value in the primary prevention of cardiovascular events even in patients who are at high risk. This study helps to give more strength to this point. Perhaps now is the time for a rethink in clinical practice and change in guidelines which recommend the use of aspirin in high risk individuals with no existing cardiovascular disease.

Adipose-derived stem cells as a therapy for cardiovascular diseases ?

Sun, 11 Feb 2007 12:45:32 PST

( from http://www.rxpgnews.com )

Patients in the study will receive their own adult stem and regenerative cells, thereby avoiding the risk of rejection or disease transmission that exists with donor stem cells and the controversy associated with embryonic stem cells.

Cytori Therapeutics (NASDAQ:CYTX) (FWB:XMPA) and Hospital Gregorio Maranon in Madrid, Spain treated the first patient in Cytori's randomized clinical trial investigating the safety and feasibility of adipose-derived stem and regenerative cells as a therapy for cardiovascular disease.

The study, designated as the 'PRECISE' trial, will enroll patients suffering from chronic myocardial ischemia, a severe form of end-stage coronary artery disease, which is estimated to affect hundreds of thousands of patients in Europe and the United States. Patients in the study will receive their own adult stem and regenerative cells, thereby avoiding the risk of rejection or disease transmission that exists with donor stem cells and the controversy associated with embryonic stem cells. Once introduced into a patient's heart, the cells have shown preclinically to help the body improve blood supply that can restore circulation to the heart.

"Patients with chronic heart disease today have few options making this an important milestone for the affected patients and doctors that treat them," said Marc H. Hedrick, M.D., President for Cytori Therapeutics. "This study is designed to show unequivocally whether the cells from our Celution System(TM) can be safely introduced into the heart. Our ultimate goal is to asses the clinical therapeutic effect of the cells, which were shown in preclinical studies to significantly improve heart function."

Adipose Tissue: Rich Cell Source

Adipose tissue, commonly known as fat, is the human body's richest known source of stem cells, as well as other cells that are believed to contribute to repair and healing, referred to as "regenerative cells." Due to its abundance and accessibility in the body, adipose tissue represents an ideal source for immediate access to a patient's own stem and regenerative cells.

The Celution(TM) System

For the PRECISE study, stem and regenerative cells are obtained at the bedside from the patients' own adipose tissue and made available in real-time using Cytori's Celution(TM) System. The Celution(TM) System automates and standardizes the complex process that releases stem and regenerative cells locked within adipose tissue. Adipose tissue is removed from the patient using a minor liposuction-like procedure, placed into the system and, with the touch of a button, processed. About an hour later, a prescribed dose of stem and regenerative cells are delivered to the patient.

Clinical Trial Details

The PRECISE study will evaluate the safety and feasibility of using adipose-derived stem and regenerative to treat 36 patients with chronic myocardial ischemia whom cannot be effectively treated by other means. The cells will be processed with the Celution(TM) System in the catheterization lab so they are available for the physician to re-inject into damaged heart muscle in about an hour using the NOGA(R) mapping and delivery system. A variety of clinical functional and imaging endpoints will be assessed in the study. The outcomes of the study will be evaluated after a six month follow-up period.

The PRECISE study is being conducted at the Hospital General Universitario Gregorio (HGU G) Maranon in Madrid, Spain. Professor Francisco Fernandez-Aviles, professor of cardiovascular medicine and chief of cardiology service at HGU G Maranon, and Dr. Emerson Perin, director of the New Interventional Cardiovascular Technology and director of the Stem Cell Center at the Texas Heart Institute will serve as co-principal investigators.

"Cytori's stem cell technology has the potential to become the next major advancement in cardiovascular disease care," said Dr. Aviles. "Their device is user-friendly and enables the delivery of patient's cells at the bedside without ever leaving the catheterization lab."

"These cells may be optimal for targeting cardiovascular disease due to their ability to promote blood vessel growth," said Dr. Perin. "This primary mode of action demonstrated in pre-clinical studies could result in significant clinical benefit."

Pre hypertension best managed by early pharmacological intervention

Sun, 19 Mar 2006 02:42:37 PST

( from http://www.rxpgnews.com ) Patients experiencing high normal blood pressure (HNBP), a precursor to hypertension, may benefit from early treatment with pharmacological therapy, according to new research presented today at the American College of Cardiology's 55th Annual Scientific Session. HNBP, often referred to as "prehypertension," is associated with double the normal risk of heart attacks and strokes. ACC.06 is the premier cardiovascular medical meeting, bringing together more than 30,000 cardiologists to further breakthroughs in cardiovascular medicine.

The Trial of Preventing Hypertension (TROPHY) is a four-year, multi-center trial evaluating the safety and potential benefit of early drug therapy in patients with high normal blood pressure (HNBP, 130 to 139 mm Hg and/or 85-89). A total of 785 patients in the trial (average entry blood pressure of 134/84.8) were randomized to 16 mg of candesartan or placebo and underwent regular blood pressure screenings, along with non-pharmacological blood pressure lowering techniques. After two years, the drug-treated group was switched to placebo, and all continued on placebo for the remaining two years. Of the enrolled patients, 448 developed hypertension.

The study endpoints measured for the frequency of diagnosed hypertension in the patients and the time to that diagnosis. Hypertension was diagnosed in patients who met the following criteria over four years: a) blood pressure was at least or greater than 140 and/or 90 mm Hg at three different clinic visits, b) clinic blood pressure was >/= 160 and/or 100 mm Hg at any single visit, c) physicians detected organ damage or other conditions requiring active treatment. Serious adverse events on the drug were low, including only 1.2 percent cardiovascular events, deeming the protocol safe.

"Prehypertension is currently treated by lifestyle modification, but this form of treatment has had little effect on public health," said Stevo Julius, M.D., Professor Emeritus of Medicine and Physiology at the University of Michigan, Ann Arbor and principal investigator of the TROPHY Trial. "It was therefore appropriate to investigate whether treatment with blood pressure-lowering drugs in this early phase of hypertension is feasible and whether it would slow down the transition from "prehypertension" to treatment-requiring hypertension."

Patients should not discontinue clopidogrel without consultation

Sat, 18 Mar 2006 02:39:37 PST

( from http://www.rxpgnews.com ) Recent media reports regarding the results of the CHARISMA Trial may be misinterpreted by patients with coronary stents and other conditions*, causing these patients to inappropriately stop taking the anti-clotting drug clopidogrel (Plavix®). Patients taking Plavix® for any reason should consult with their cardiologist or other health care provider before stopping this medication.

The CHARISMA Trial was presented at the Annual Scientific Sessions of the American College of Cardiology on Sunday, March 12 in Atlanta and simultaneously published in the New England Journal of Medicine. Although the CHARISMA trial showed no benefit to combining Plavix® and aspirin and for certain patients, this study does not invalidate use of the drug for approved indications, such as stenting. Certain other patients are given Plavix® after hospitalization for heart attack or stroke. Patients with these conditions must discuss the benefits and risks of anti-clotting medication with their health care provider and should not stop Plavix® on their own. Discontinuation of Plavix® in patients with recently-placed stents can cause clot formation within the stent, resulting in serious harm or death.

* According to the 2006 ACC/AHA/SCAI Guideline Update for Percutaneous Coronary Intervention (PCI), Class I recommendations indicate the use of aspirin and clopidigrel in patients undergoing angioplasty with stent implantation (contraindications include aspirin resistance, allergy or risk of bleeding).

Clopidogrel and aspirin combination fails to show long term beneficial affects in stable vascular patients

Sat, 18 Mar 2006 02:16:37 PST

( from http://www.rxpgnews.com ) While the CHARISMA trial (Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management and Avoidance) results have shown no benefit overall of the combination of Clopidogrel and aspirin in the long term in stable vascular patients, and some indication of harm in patients in primary prevention, the ESC would like to remind patients that dual antiplatelet therapy is an essential, approved and recommended therapy for one year in patients post ACS without ST-segment elevation, and for at least six months post stenting.

Patients taking Clopidogrel (Plavix®) should not stop taking the anti-clotting drug without first consulting their physician, said ESC spokesperson on Acute Coronary Syndromes, Professor Freek Verheugt from Radboud University Medical Center, Nijmegen, Netherlands. Patients who stop taking Clopidogrel without seeking the advice of their doctor may be putting themselves in grave danger.

For more information, please see current ESC guidelines for Percutaneous Coronary Intervention (1) (http://www.escardio.org/knowledge/guidelines/PCI-Guidelines.htm) and Acute Coronary Syndromes in Patients Presenting Without Persistent ST-Segment Elevation (2) (http://www.escardio.org/knowledge/guidelines/Management_ACS_without_persistent_ST-segment_elevation.htm).

The CHARISMA trial was presented at the Annual Scientific Sessions of the American College of Cardiology in March 2006 and simultaneously published on the website of The New England Journal of Medicine (http://content.nejm.org/).

The European Society of Cardiology (ESC)

The ESC represents more than 45,000 cardiology professionals across Europe and the Mediterranean. Its mission is to improve the quality of life of the European population by reducing the impact of cardiovascular disease.

The ESC achieves this through a variety of scientific and educational activities including the coordination of: clinical practice guidelines, education courses and initiatives, pan-European surveys on specific disease areas and the ESC Annual Congress, the largest medical meeting in Europe. Furthermore, the ESC promotes cardiovascular disease prevention messages to the general public, most notably during its annual 'For Your Heart's Sake' event, a fun yet educational event offering risk assessment and prevention advice, held in parallel to the Congress each year.

Bluhm Cardiovascular Institute Surgeons Implant Heart Pump in Comparative Study of Two Devices

Sat, 19 Nov 2005 02:00:38 PST

( from http://www.rxpgnews.com ) Chicago's first participant in the RELIANT (Randomized Evaluation of the Novacor(r) LVAS In A Non-Transplant Population) research study recently went home from Northwestern Memorial Hospital.

Percy Pinkdon, a 70-year-old Chicago man, suffered from irreversible end-stage cardiomyopathy, a weakening of the heart muscle that affects its ability to pump blood.

He received unsuccessful cardiac treatments at other hospitals and an existing bone marrow abnormality ruled out a heart transplant. A friend recommended he come to the Bluhm Cardiovascular Institute at Northwestern Memorial Hospital where he learned about a first-of-its-kind, national, multi-center clinical trial that compares heart pumps from two different manufacturers - the Novacor Left Ventricular Assist System (LVAS) and the standard device, the HeartMate VE LVAS - as destination therapy or a permanent treatment for severely ill patients who are not candidates for a heart transplant.

"The field of heart pump technology is evolving. This research trial is important because we need to understand what type of pump will work best in each patient," said Pinkdon's surgeon, Edwin McGee, MD, surgical director, Advanced Heart Failure Program at the Bluhm Cardiovascular Institute and assistant professor of surgery at Northwestern University's Feinberg School of Medicine.

Heart pumps were initially approved as a "bridge-to-transplant," to assist a person's ailing heart until a donor heart could be found for transplantation. Three years ago, the Food and Drug Administration (FDA) gave approval for the first time for a heart pump to be used as destination therapy.

Left ventricular assist systems assume the pumping function of the left ventricle of the heart, which pumps blood to the large blood vessel that sends blood to the rest of the body. The systems include an implantable heart pump and mobile external components, connected through a line in the skin that powers the pump. Patients typically carry the power components, which are about the size of a deck of cards, in a holder around the waist. "Destination therapy or permanent placement of ventricular assist systems is in its infancy, but the technology is improving constantly and rapidly," says John O'Connell, MD, director of the Bluhm Cardiovascular Institute's Center for Heart Failure. "Soon a proven totally implantable device will be available. While transplantation can be very effective for end stage heart disease, only 2000 are done annually in the United Sates and the number who could benefit from replacement therapy may be as many as 250,000. However, currently destination therapy is available only to those who cannot receive a transplant because of non-cardiac conditions that rule out transplant."

"The results of a clinical trial in 2001 showed that participants with end-stage heart failure who are not transplant candidates live longer, fuller lives if they receive an LVAS as opposed to being treated with optimal medical therapy," said Dr. McGee. "These pumps are the best option for those in the worst stages of heart disease who, for whatever reason, are not candidates for a heart transplant."

"Before getting a heart pump, Mr. Pinkdon was about as sick as you can get," says Dr. McGee. "The highest doses of medicine were no longer working. His heart was not pumping adequate amounts of blood to his body. We had to implant an intra-aortic balloon pump to reduce the workload of his heart and to improve flow of his blood to the coronary arteries. He required intubation and was placed on a ventilator."

Mr. Pinkdon had the device implanted in late August and after a nearly two-month recovery at Northwestern Memorial, he says, "I feel great. I'm no longer out of breath or in pain."

"We are very happy with his progress," says Dr. McGee. "With either of the pumps we're studying, participants should have more energy and can basically return to their normal lives."

The Bluhm Cardiovascular Institute, which relaunched its heart transplant program this spring, offers world-class heart services from evaluation to follow-up. "We want to see those patients who have been told nothing else can be done for their heart conditions," said, Patrick McCarthy, MD, co-director of the Bluhm Cardiovascular Institute of Northwestern Memorial Hospital and chief, Cardiothoracic Surgery, Northwestern Memorial. "We've performed surgery on many patients who've been told they aren't surgical candidates and have done beautifully with complex bypasses or valve repairs. However, when repairs are not possible, we have a team with the experience and knowledge to evaluate patients and offer transplant if at all possible. If not, we can offer the latest generation of heart pumps, and it is hoped that participants will do well with these."

"Cooperation of the primary care physician, cardiologist and heart surgeon is critical to an optimal result,," says O'Connell, who was one of Mr. Pinkdon's cardiologists. "We have assembled a team of nurses, cardiologists and surgeons that work together to personalize the approach to the management of care with the goal of achieving the best outcome possible for each of our patients."

Ground-breaking heart stem cell trial (REGENERATE) now underway

Thu, 13 Oct 2005 15:24:38 PST

( from http://www.rxpgnews.com ) Doctors at Barts and The London NHS Trust have launched the UKs first large-scale clinical trial designed to find out if a patients own stem cells can be used to treat heart disease.

The ground-breaking research, which is being funded by the Heart Cells Foundation charity, will involve 700 patients over the next four years.

The trial is made up of three randomised-controlled studies. The first study will involve 300 patients whose hearts are failing because of heart disease or a previous heart attack. The second study will involve 200 patients whose hearts are failing specifically because of dilated cardiomyopathy a heart muscle disorder. The third study will involve 200 patients who have just had a heart attack.

Doctors are testing three different stem cell therapy techniques as part of the trial. Some patients will have stem cells extracted from bone marrow in their hip and injected into their major coronary arteries or directly into their heart in a minimally invasive operation. Others will receive injections of growth factor drugs to try to cause stem cells to spill out of their bone marrow and into their blood without the need for the operation.

Consultant Cardiologist Dr Anthony Mathur, who is leading the research, said: "This is one of the biggest and most comprehensive trials of its kind in the world. Our studies will tell us if adult stem cells in bone marrow can repair damaged hearts and if so how these cells should be administered to patients. There is growing evidence to suggest that stem cells may benefit people with serious heart conditions, such as heart failure or those who have had heart attacks.

"Stem cells are the bodys master cells. They are unique because unlike other cells they can turn into almost any other type of cell in the body. Our studies will determine if adult stem cells in bone marrow can repair damaged heart muscle. Heart disease is one of the UKs biggest killers. It affects almost 2.7m people and claims 120,000 lives each year. If proven to work, these cells could revolutionise the way we treat heart disease and could transform the lives of millions of people not only in the UK but around the world."

Ian Rosenberg, Founder of the Heart Cells Foundation, said: "Two years ago, I was given just a couple of months to live. I travelled to Germany where they have pioneered stem cell therapy for heart disease to have my own stem cells injected into my heart. Within a matter of months, I was able to do things I could only dream of doing before, such as walking up and down stairs or playing golf. Stem cell therapy has given me years I never thought I would have.

"I set up the Heart Cells Foundation so that others may benefit from this new and exciting science. We have launched an appeal to raise the £6m needed to fund this research at Barts and The London NHS Trust. We have already raised £1m, enabling this historic trial to get underway. I believe this trial will provide us with the clear evidence we need to ensure others can benefit from stem cell therapy."