 |
|
NHLBI stops study of pulmonary hypertension treatment in sickle cell patients
July 29, 2009The National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health has stopped a clinical trial testing a drug treatment for pulmonary hypertension in adults with sickle cell disease nearly one year early due to safety concerns. In an interim review of safety data from 33 participants who completed 16 weeks of treatment, researchers found that, compared to participants on placebo (dummy pill), participants taking sildenafil (Revatio) were significantly more likely to have serious medical problems. The most common problem was episodes of severe pain called sickle cell crises, which resulted in hospitalization. No deaths have been associated with the drug in the clinical trial.
Known as walk-PHaSST, the study was the first multicenter, randomized clinical trial to test the safety and effectiveness of sildenafil for pulmonary hypertension in patients with sickle cell disease, one of the most common genetic blood disorders in the United States. Pulmonary hypertension is a debilitating condition of high blood pressure in the arteries that carry blood to the lungs, which can lead to heart failure and death. Approximately 30 percent of sickle cell disease patients develop pulmonary hypertension, and even mild levels of pulmonary hypertension have been associated with sudden death in people with sickle cell disease.
"The increase in sickle cell medical problems is concern enough for us to stop this clinical trial to protect the safety of our participants," said NHLBI Director Elizabeth G. Nabel, M.D. "We will continue to look into the possible causes of these preliminary results. In the meantime, we encourage patients with sickle cell disease who are taking sildenafil for pulmonary hypertension to talk with their physicians about the potential risks and benefits of the medication and what actions they should consider, including whether to taper off this medication and how to best manage both sickle cell disease and pulmonary hypertension."
Because the medical problems experienced in walk-PHaSST were complications specific to sickle cell disease, "The findings of the walk-PHaSST study should not be applied to other groups of patients with pulmonary hypertension where the drug has been found to be safe and effective," Nabel added.
Researchers are conducting extensive analyses of the study results, which could contribute to recommendations for treating pulmonary hypertension in patients with sickle cell disease. They will prepare reports of their research for publication in peer-reviewed journals.
The NHLBI stopped the study on July 7, 2009, based on the unanimous recommendations of the Pulmonary Complications of Sickle Cell Disease Data and Safety Monitoring Board (DSMB), an independent advisory group that has been monitoring the study since it began. This DSMB is composed of experts in sickle cell disease, lung disease, statistics, and bioethics.
Participants in walk-PHaSST have discussed the preliminary findings of the study with their study clinicians. They have been instructed to taper sildenafil treatment over a period of three to seven days to minimize problems associated with immediate withdrawal from the drug, such as worsening of symptoms of pulmonary hypertension. Researchers will continue to monitor participants and conduct further analyses to assess the findings.
Walk-PHaSST was designed to determine whether sildenafil lessens the symptoms of pulmonary hypertension, such as shortness of breath, by improving heart and lung function, in individuals with sickle cell disease who develop pulmonary hypertension. The primary outcome measure was the results of a six-minute walk test, a standard indicator of a person's heart and lung function. Hence, the name walk-PHaSST reflects the primary test used to assess effectiveness of the treatment ("walk" test) for Pulmonary Hypertension and Sickle Cell Disease with Sildenafil Therapy. Researchers also evaluated the safety of the drug for sickle cell disease patients through reports of adverse effects and laboratory tests.
Sildenafil is approved by the Food and Drug Administration for use in patients with pulmonary hypertension. In general, the drug treats pulmonary hypertension by relaxing the blood vessels in the lungs to allow blood to flow more easily. Since sildenafil is not FDA-approved to treat pulmonary hypertension in patients with sickle cell disease, the walk-PHaSST study was conducted under an investigational new drug application. The FDA was notified of the termination of the study on July 14.
Walk-PHaSST began recruiting participants in July 2007 and enrolled 74 patients over the age of 19 (average age 45). Participants had sickle cell disease and mild to severe pulmonary hypertension. They were randomly assigned to receive sildenafil or placebo for 16 weeks. Participants could also receive other therapies as needed to manage sickle cell and related complications. After completing the study treatment (or placebo), participants could choose to be part of the open-label follow-up phase of the study and continue to be assessed for up to one year. In the open-label study, participants and clinicians knew that sildenafil was being taken. When the study was stopped, 33 participants had completed the clinical trial.
Researchers found that 38 percent of participants taking sildenafil had serious adverse effects -- primarily sickle cell pain crises -- compared to 8 percent of participants in the placebo group.
"Although these preliminary results are disappointing, we expect that the study's results, once fully analyzed, will provide important insights into the role of pulmonary hypertension in sickle cell disease," said Mark Gladwin, M.D., lead investigator of walk-PHaSST and director of the Vascular Medicine Institute at the University of Pittsburgh. Gladwin is also a special volunteer for the NHLBI and was formerly a senior investigator with the Critical Care Medicine Department at the NIH Clinical Center and chief of the NHLBI Pulmonary and Vascular Medicine Branch.
The design of the walk-PHaSST study was based on extensive evidence that sildenafil improves pulmonary hypertension regardless of its cause and on results of a small, open-label, nonrandomized pilot study led by Gladwin while he was at the NIH. The pilot study evaluated 12 sickle cell patients with mild or moderate pulmonary hypertension who were being treated with sildenafil and with hydroxyurea, a drug known to help reduce the numbers of episodes of sickle cell pain crises and acute chest syndrome, as well as hospitalizations and blood transfusions needed. In 2005, Gladwin and his colleagues reported that after about 6 months, sildenafil was well tolerated, decreased pulmonary blood pressure, and increased exercise capacity.
"Walk-PHaSST emphasizes the importance of multi-site, blinded, randomized clinical trials to increase our understanding of both the benefits and the potential risks of specific treatments," noted Jonathan C. Goldsmith, M.D., NHLBI project officer of walk-PHaSST. "As with all clinical studies, patient safety is paramount."
Walk PHaSST was conducted at the following locations:
* Children's Hospital, Oakland, Calif.
* University of Colorado, Denver
* Howard University Hospital, Washington, D.C.
* University of Illinois at Chicago
* Johns Hopkins Medical Institutions, Baltimore
* NIH Clinical Center, Bethesda, Md.
* Albert Einstein College of Medicine, New York City
* Columbia University, New York City
* Children's Hospital, Pittsburgh
* Imperial College London and Hammersmith Hospital, London, England
Rho Inc. of Chapel Hill, N.C., serves as the data coordinating center. Pfizer provided the treatment drug and placebo for the study.
Sickle cell anemia affects millions of people worldwide. An estimated 70,000 to 100,000 people in the United States have sickle cell disease, primarily African Americans and, to a lesser degree, people whose families come from South or Central America. Patients with this disease have abnormal hemoglobin molecules in their red blood cells. The abnormal molecules deform the red blood cells, causing them to clump together and block blood flow through blood vessels, leading to painful sickle cell crises, organ damage, and anemia. Life-threatening complications include infections, acute chest syndrome, stroke, and pulmonary hypertension. Painful crises are the leading cause of emergency room visits and hospitalizations of people who have sickle cell anemia.
There are currently no established guidelines for treating pulmonary hypertension in patients with sickle cell disease. Pulmonary hypertension can lead to heart failure and death as the heart must work harder to push blood into the lungs. In general, intensive management of sickle cell disease through hydroxyurea, blood transfusions, and/or bone marrow transplantation may be indicated. Other treatment options may include blood-thinning medicines, diuretics, and oxygen therapy.
"As new treatments have evolved over the past several years, sickle cell patients are living longer than in previous decades, presenting new challenges for managing chronic problems and complications such as pulmonary hypertension," noted Susan Shurin, MD, NHLBI deputy director and a hematologist. "The NHLBI continues to maintain a strong commitment to supporting research in adults as well as in children to discover new and better ways to improve quality of life and survival for patients with sickle cell disease."
NIH/National Heart, Lung and Blood Institute
Because the medical problems experienced in walk-PHaSST were complications specific to sickle cell disease, "The findings of the walk-PHaSST study should not be applied to other groups of patients with pulmonary hypertension where the drug has been found to be safe and effective," Nabel added.
Researchers are conducting extensive analyses of the study results, which could contribute to recommendations for treating pulmonary hypertension in patients with sickle cell disease. They will prepare reports of their research for publication in peer-reviewed journals.
The NHLBI stopped the study on July 7, 2009, based on the unanimous recommendations of the Pulmonary Complications of Sickle Cell Disease Data and Safety Monitoring Board (DSMB), an independent advisory group that has been monitoring the study since it began. This DSMB is composed of experts in sickle cell disease, lung disease, statistics, and bioethics.
Participants in walk-PHaSST have discussed the preliminary findings of the study with their study clinicians. They have been instructed to taper sildenafil treatment over a period of three to seven days to minimize problems associated with immediate withdrawal from the drug, such as worsening of symptoms of pulmonary hypertension. Researchers will continue to monitor participants and conduct further analyses to assess the findings.
Walk-PHaSST was designed to determine whether sildenafil lessens the symptoms of pulmonary hypertension, such as shortness of breath, by improving heart and lung function, in individuals with sickle cell disease who develop pulmonary hypertension. The primary outcome measure was the results of a six-minute walk test, a standard indicator of a person's heart and lung function. Hence, the name walk-PHaSST reflects the primary test used to assess effectiveness of the treatment ("walk" test) for Pulmonary Hypertension and Sickle Cell Disease with Sildenafil Therapy. Researchers also evaluated the safety of the drug for sickle cell disease patients through reports of adverse effects and laboratory tests.
Sildenafil is approved by the Food and Drug Administration for use in patients with pulmonary hypertension. In general, the drug treats pulmonary hypertension by relaxing the blood vessels in the lungs to allow blood to flow more easily. Since sildenafil is not FDA-approved to treat pulmonary hypertension in patients with sickle cell disease, the walk-PHaSST study was conducted under an investigational new drug application. The FDA was notified of the termination of the study on July 14.
Walk-PHaSST began recruiting participants in July 2007 and enrolled 74 patients over the age of 19 (average age 45). Participants had sickle cell disease and mild to severe pulmonary hypertension. They were randomly assigned to receive sildenafil or placebo for 16 weeks. Participants could also receive other therapies as needed to manage sickle cell and related complications. After completing the study treatment (or placebo), participants could choose to be part of the open-label follow-up phase of the study and continue to be assessed for up to one year. In the open-label study, participants and clinicians knew that sildenafil was being taken. When the study was stopped, 33 participants had completed the clinical trial.
Researchers found that 38 percent of participants taking sildenafil had serious adverse effects -- primarily sickle cell pain crises -- compared to 8 percent of participants in the placebo group.
"Although these preliminary results are disappointing, we expect that the study's results, once fully analyzed, will provide important insights into the role of pulmonary hypertension in sickle cell disease," said Mark Gladwin, M.D., lead investigator of walk-PHaSST and director of the Vascular Medicine Institute at the University of Pittsburgh. Gladwin is also a special volunteer for the NHLBI and was formerly a senior investigator with the Critical Care Medicine Department at the NIH Clinical Center and chief of the NHLBI Pulmonary and Vascular Medicine Branch.
The design of the walk-PHaSST study was based on extensive evidence that sildenafil improves pulmonary hypertension regardless of its cause and on results of a small, open-label, nonrandomized pilot study led by Gladwin while he was at the NIH. The pilot study evaluated 12 sickle cell patients with mild or moderate pulmonary hypertension who were being treated with sildenafil and with hydroxyurea, a drug known to help reduce the numbers of episodes of sickle cell pain crises and acute chest syndrome, as well as hospitalizations and blood transfusions needed. In 2005, Gladwin and his colleagues reported that after about 6 months, sildenafil was well tolerated, decreased pulmonary blood pressure, and increased exercise capacity.
"Walk-PHaSST emphasizes the importance of multi-site, blinded, randomized clinical trials to increase our understanding of both the benefits and the potential risks of specific treatments," noted Jonathan C. Goldsmith, M.D., NHLBI project officer of walk-PHaSST. "As with all clinical studies, patient safety is paramount."
Walk PHaSST was conducted at the following locations:
* Children's Hospital, Oakland, Calif.
* University of Colorado, Denver
* Howard University Hospital, Washington, D.C.
* University of Illinois at Chicago
* Johns Hopkins Medical Institutions, Baltimore
* NIH Clinical Center, Bethesda, Md.
* Albert Einstein College of Medicine, New York City
* Columbia University, New York City
* Children's Hospital, Pittsburgh
* Imperial College London and Hammersmith Hospital, London, England
Rho Inc. of Chapel Hill, N.C., serves as the data coordinating center. Pfizer provided the treatment drug and placebo for the study.
Sickle cell anemia affects millions of people worldwide. An estimated 70,000 to 100,000 people in the United States have sickle cell disease, primarily African Americans and, to a lesser degree, people whose families come from South or Central America. Patients with this disease have abnormal hemoglobin molecules in their red blood cells. The abnormal molecules deform the red blood cells, causing them to clump together and block blood flow through blood vessels, leading to painful sickle cell crises, organ damage, and anemia. Life-threatening complications include infections, acute chest syndrome, stroke, and pulmonary hypertension. Painful crises are the leading cause of emergency room visits and hospitalizations of people who have sickle cell anemia.
There are currently no established guidelines for treating pulmonary hypertension in patients with sickle cell disease. Pulmonary hypertension can lead to heart failure and death as the heart must work harder to push blood into the lungs. In general, intensive management of sickle cell disease through hydroxyurea, blood transfusions, and/or bone marrow transplantation may be indicated. Other treatment options may include blood-thinning medicines, diuretics, and oxygen therapy.
"As new treatments have evolved over the past several years, sickle cell patients are living longer than in previous decades, presenting new challenges for managing chronic problems and complications such as pulmonary hypertension," noted Susan Shurin, MD, NHLBI deputy director and a hematologist. "The NHLBI continues to maintain a strong commitment to supporting research in adults as well as in children to discover new and better ways to improve quality of life and survival for patients with sickle cell disease."
NIH/National Heart, Lung and Blood Institute
Pulmonary Hypertension Current Events and Pulmonary Hypertension News RSSDrug for erectile dysfunction improves heart function in young heart-disease patients
Heart function significantly improved in children and young adults with single-ventricle congenital heart disease who have had the Fontan operation following treatment with sildenafil, a drug used to treat erectile dysfunction and pulmonary hypertension, say researchers from The Children's Hospital of Philadelphia.
Key player identified in cascade that leads to hypertension-related kidney damage
A key player in a cascade that likely begins with stress and leads to high blood pressure and kidney damage has been identified by researchers who say the finding may lead to better ways to control both.
Experts unveil new CVD guidelines and position papers
Several new guidelines and position papers offering the most up to date information to ensure that clinicians practice evidence-based medicine were released at the Canadian Cardiovascular Congress 2009 this week.
UC San Diego researchers reverse pulmonary arterial hypertension in mouse models
Researchers at the University of California, San Diego, have identified a key protein that promotes the development of pulmonary arterial hypertension in humans and mice.
Endothelin-Related Drugs Benefit Patients With Pulmonary Hypertension
Recent research to block the effects of endothelin, a powerful substance that constricts blood vessels and stimulates cell growth, has led to successful treatment of pulmonary arterial hypertension and provides hope for treating other chronic diseases.
International conference on endothelin
One of the most intriguing developments in recent medical science is the discovery of the human chemical endothelin (ET).
Pulmonary CT angiography identifies disease and injury beyond the pulmonary arteries in children
Computed tomography angiography (CTA) can identify abnormalities and injury beyond the pulmonary arteries, including broken bones and heart disease, according to a study published in the September issue of the American Journal of Roentgenology (AJR)
Taking dex can improve high altitude exercise capacity in certain climbers
Taking dexamathasone prophlyactically may improve exercise capacity in some mountaineers, according to Swiss researchers. Dexamathasone, known popularly to climbers as "dex," has been used for years to treat altitude-related symptoms in mountaineers, but has never been tested for its ability to improve exercise capacity at high altitude.
Severe obesity increases risks of health problems during surgery
Healthcare providers must carefully consider the unique risk factors related to severe obesity in patients undergoing all types of surgery, according to an American Heart Association scientific advisory published in Circulation: Journal of the American Heart Association.
Gene therapy technique thwarts cancer by cutting off tumor blood supply
University of Florida researchers have come up with a new gene therapy method to disrupt cancer growth by using a synthetic protein to induce blood clotting that cuts off a tumor's blood and nutrient supply.
More Pulmonary Hypertension Current Events and Pulmonary Hypertension News Articles
 |
Pulmonary Hypertension (Contemporary Cardiology) by Nicholas S. Hill (Author), Nicholas S. Hill (Editor), Harrison W. Farber (Editor) This timely volume addresses the areas of pathophysiology and therapy of pulmonary hypertension, which have seen exciting developments over the past decade. The discoveries of endothelin overexpression as well as prostacyclin and nitric oxide deficiency in association with pulmonary hypertension have led to important therapeutic insights. In addition, the identification of genes associated with pulmonary hypertension has just begun to open the door to new pathophysiologic insights. The new therapies have led to significant improvements in patient function, quality of life and survival. This book will be of interest not only to cardiologists, pulmonary specialists and rheumatologists, but also many nurses and pharmacotherapists are becoming increasingly involved in the therapy of... |
|
Pulmonary Hypertension: A Patient's Survival Guide by Gail Boyer Hayes (Author) | |
 |
Identifying Pulmonary Hypertension Pulmonary Hypertension is a rare, complex disease of the heart and lungs. It most commonly strikes women in childbearing years, though it can affect all ages, races and both sexes. This program will identify what pulmonary hypertension is, and how it is treated. Though there is not yet a cure for this illness, treatments have emerged over the last decade, giving patients hope for a longer, healthier life. Meet patients who are living with pulmonary hypertension and demonstrate how to improve your quality of life. We'll also outline the genesis of the Pulmonary Hypertension Association, and illustrate the power people can have to organize, draw attention to a cause and work to improve the lives of patients and families coping with serious illnesses. This program is part of the award... |
 |
Pulmonary Hypertension Awareness Ribbon Mouse Pad by MyHeritageWear.com The Pulmonary Hypertension Ribbon proudly displayed on a mouse pad. There is no better way to achieve awareness for the meaning of the Pulmonary Hypertension Ribbon than to display it on your mouse pad for everyone to see. The mouse pad measures at 9.25 x 7.75, it is machine washable, and the colors will not fade or run. Start gaining awareness today by presenting your Pulmonary Hypertension Ribbon mouse pad at work or at home. It is certain to keep your mouse rolling in style all while gaining support and awareness! |
 |
Hypertril for Pulmonary Hypertension - Normalize blood pressure levels - Bio-Enhanced Extraction Technology by HP-Hypertril A number of studies have demonstrated that increased free radical activity plays an important role in all cases of high blood pressure, because increased free radicals cause cellular damage and inactivate nitric oxide. Nitric oxide, an important molecular regulator of blood pressure, helps control blood pressure by dilating blood vessels. Antioxidants, powerful free radical scavengers, may help restore activities of nitric oxide and help to control blood pressure. This is the main theoretical basis of HypertrilTM. In addition to antioxidant activities, Hypertril also provides essential nutrients to support blood pressure control and improve circulation. In a study performed at the Institut de Cardiologie de Montreal, Canada, Hypertril demonstrated a significant reduction in MAP (Mean... |
 |
Pulmonary Arterial Hypertension: Diagnosis and Evidence-Based Treatment by Robyn Barst (Editor) First book dedicated to this disease, previously thought to be incurable, but with the advent of new drugs, now amenable to management and a much improved prognosis for patients From the PAH Association, the leading experts in field Incorporates the latest AACP management guidelines Includes evidence-based treatment algorithms based on the recently updated ACCP Guidelines for Medical Treatment Aimed at specialists in pulmonology and cardiovascular disease, this volume provides the clinician with the most up to date information on the effective management of PAH |
 |
Balanceuticals Blood Circulator Dietary Supplement Capsules, 500 mg, 60-Count Bottle by Balanceuticals Dietary Supplement. 100% Natural. Made under Supervision by China Academy of Traditional Chinese Medicine. Made of medicinal rhubarb, prepared rehmannia root, common peony root, peach seed, bitter apricot seed, licorice root, scute, dun fly, gadfly, leech, June beetle, this time-honored formula is used in Chinese medicine to promote micro-circulation, increase blood flow to heart muscles, open and clear arteries, inhibit intestinal adhesion, soothe the liver, remove stasis and maintain healthy blood circulation and regular menses. This statement has not been evaluated by the FDA. This product is not intended to diagnose, treat, cure or prevent any disease. |
 |
Pulmonary Hypertension Medical Guide by Qontro Medical Guides (Author) The Pulmonary Hypertension Medical Guide is a publication which has been designed to better help readers understand Pulmonary Hypertension. This Qontro Medical Guide has been designed with the reader in mind, and is a useful information source for readers at all levels looking to learn more about Pulmonary Hypertension. The Pulmonary Hypertension Medical Guide is highly recommended for those interested in understanding and learning more about Pulmonary Hypertension. |
 |
A Clinician's Guide to Pulmonary Arterial Hypertension: Pocketbook, Second Edition by Stewart Simon (Author) A Clinician's Guide to Pulmonary Arterial Hypertension, Second Edition enhances the overall 'PAH awareness' of the wider clinical community, and outlines the need for screening, effective diagnosis and beneficial treatment. Topics include: |
 |
The Official Patient's Sourcebook on Primary Pulmonary Hypertension by James N. Parker (Editor), Philip M. Parker (Editor) This book has been created for patients who have decided to make education and research an integral part of the treatment process. Although it also gives information useful to doctors, caregivers and other health professionals, it tells patients where and how to look for information covering virtually all topics related to primary pulmonary hypertension (also familial primary pulmonary hypertension; idiopathic pulmonary hypertension; primary obliterative pulmonary vascular disease; primary pulmonary vascular disease; pulmonary hypertension), from the essentials to the most advanced areas of research. The title of this book includes the word official. This reflects the fact that the sourcebook draws from public, academic, government, and peer-reviewed research. Selected readings from... |
| © 2009 BrightSurf.com |