Duke Clinical Research Institute

Durham, NC, United States

Duke Clinical Research Institute

Durham, NC, United States
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WILMINGTON, Del.--(BUSINESS WIRE)--AstraZeneca today announced top-line results from the Phase IIIb/IV EXSCEL (EXenatide Study of Cardiovascular Event Lowering) trial. The trial compared the effect of once-weekly Bydureon (exenatide extended-release) for injectable suspension versus placebo, when added to usual type-2 diabetes care, on the risk of MACE, a composite endpoint of CV death, non-fatal myocardial infarction or non-fatal stroke, in adults with type-2 diabetes (T2D) at a wide range of CV risk. The EXSCEL trial met its primary safety objective of non-inferiority for MACE. These results address the US Food and Drug Administration (FDA) requirement that medicines to treat T2D are not associated with an increase in CV risk. Fewer CV events were observed in the Bydureon arm of the trial, however, the efficacy objective of superior reduction in MACE did not reach statistical significance. Data were consistent with the known safety profile of Bydureon. Elisabeth Björk, Vice President, Head of Cardiovascular and Metabolic Diseases, Global Medicines Development, AstraZeneca said: “These top-line results from the EXSCEL trial provide robust evidence of the cardiovascular safety profile of Bydureon across a wide range of patients with type-2 diabetes. Furthermore, the trial design and broad inclusion criteria of EXSCEL offer physicians relevant data applicable to clinical practice.” The EXSCEL trial is the largest and most inclusive patient population of any CV outcomes trial of the glucagon-like peptide-1 (GLP-1) receptor agonist class conducted to date, having included more than 14,000 patients from 35 countries. A full evaluation of the EXSCEL data is ongoing. The results will be presented at the European Association for the Study of Diabetes (EASD) annual meeting on Thursday, 14 September 2017 in Lisbon, Portugal. Most common (≥5%) and occurring more frequently than comparator in clinical trials: nausea (16.9%), diarrhea (12.7%), headache (8.0%), vomiting (6.8%), constipation (5.9%), injection-site pruritus (5.9%), injection-site nodule (5.3%), and dyspepsia (5.1%) INDICATION AND LIMITATIONS OF USE BYDUREON is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus EXSCEL is a Phase IIIb/IV, double-blind, placebo-controlled, global CV outcomes trial conducted in 35 countries and enrolled more than 14,000 patients with type-2 diabetes with or without additional CV risk factors or prior CV events. Participants were randomized to receive exenatide once-weekly 2mg or matching placebo by subcutaneous injections. EXSCEL was run jointly by two academic research organizations - the Duke Clinical Research Institute (Durham, NC, US) and the University of Oxford Diabetes Trials Unit (Oxford, UK). AstraZeneca is pushing the boundaries of science with the goal of developing life-changing medicines that aim to reduce the global burden and complications of diabetes. As a main therapy area for the company, we are focusing our research and development efforts on diverse populations and patients with significant co-morbidities, such as cardiovascular disease, obesity, non-alcoholic steatohepatitis (NASH), and chronic kidney disease. Our commitment to diabetes is exemplified by the depth and breadth of our global clinical research program This commitment is advancing understanding of the treatment effects of our diabetes medicines in broad patient populations, as well as exploring combination products to help more patients achieve treatment success earlier in their disease. Cardiovascular, renal and metabolic diseases are key areas of focus for AstraZeneca as part of the company’s strategy for achieving scientific leadership and returning to growth. By collaborating across therapeutic disciplines within the CVMD therapy area, we are addressing the underlying disorders that drive CVMD risk, with the goal of reducing morbidity, mortality and organ damage through innovative therapies. Recognizing the growing unmet needs and challenges faced by the millions of people worldwide living with these interrelated diseases, we are determined to understand how they interact and impact one another – and how they can be treated together to save more patients’ lives. AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization of prescription medicines, primarily for the treatment of diseases in three main therapy areas - Oncology, Cardiovascular & Metabolic Diseases and Respiratory. The Company also is selectively active in the areas of autoimmunity, neuroscience and infection. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information, please visit www.astrazeneca-us.com and follow us on Twitter @AstraZenecaUS.


News Article | May 11, 2017
Site: www.eurekalert.org

An analysis of data from the entire development program consisting of three trials assessing the feasibility of using a stem cell therapy (CD34+ cells) to treat patients with the most severe cases of angina, refractory angina (RA), showed a statistically significant improvement in exercise time as well as a reduction in mortality. Results from "CD34+ Stem Cell Therapy Improves Exercise Time and Mortality in Refractory Angina: A Patient Level Meta-Analysis" were presented today as a late-breaking clinical trial at the Society for Cardiovascular Angiography and Interventions (SCAI) 2017 Scientific Sessions in New Orleans. One of the warning signs of coronary artery disease is angina, or chest pain, which occurs when the heart muscle does not receive enough blood. Unlike angina pectoris or "stable angina," which can often be treated with medication, RA can be incapacitating, impacting quality of life. In the most severe cases, those with class III or IV angina, treatment options are exhausted, and patients remain severely debilitated. Unfortunately, one of the untoward consequences of the improved survival of patients with chronic ischemic heart disease is more patients with refractory angina. A meta-analysis of three trials that each showed promising results looked at injecting RA patients with autologous CD34+ cells -- which have been shown to increase blood flow -- and the therapy's effect on mortality and total exercise time (TET), an important predictor of long-term mortality. Data from 304 patients was extracted and analyzed from phase 1 (24 patients), ACT-34 and ACT-34 extension studies (168 patients), and RENEW (112 patients), which was prematurely terminated by the sponsor due to financial considerations. "The goal of this meta-analysis was to combine patient level data from three very similar trials to try understand what it would tell us," said lead investigator Tom Povsic, MD, FSCAI, associate professor at the Duke Clinical Research Institute (DCRI) and an interventional cardiologist at Duke University School of Medicine. Results showed that patients treated with CD34+ cell therapy (n=187) improved TET by 80.5 ± 12.1, 101.8 ±13.7, and 90.5 ± 14.7 seconds at three months, six months, and 12 months compared with 28.1 ± 15.7, 48.8 ± 18.2, and 39.5 ± 20.3 seconds for the placebo group (n=89), resulting in treatment effects of 52.5 (p=0.002), 52.9 (p=0.009) and 50.9 (p=0.027) seconds. The relative risk of angina was 0.90 (p=0.40), 0.81 (p=0.14), and 0.79 (p=0.17) at three months, six months, and 12 months in CD34+ treated patients. CD34+ treatment decreased mortality by 24 months (2.6 percent vs. 11.8 percent, p=0.003). In addition, major adverse cardiac events were less frequent (29.8 percent for CD34+ patients vs. 40.0 percent for the placebo group, p=0.08). "Therapies for these patients are direly needed," said Povsic, "and results from our meta-analysis are very compelling. Most importantly, the number of patients in our meta-analysis approximates those who were targeted for enrollment in RENEW, the prematurely terminated phase III study. These results suggest that had RENEW been completed, a regenerative therapy for these patients might meet criteria for approval. I still think this therapy has a lot of promise." Timothy Henry, MD, chief of cardiology at Cedars-Sinai Medical Center in Los Angeles, agrees "CD34+ cell therapy appears to be an extremely safe and effective therapy for this growing and challenging patient population with limited options." Povsic presented "CD34+ Stem Cell Therapy Improves Exercise Time and Mortality in Refractory Angina: A Patient Level Meta-Analysis" on Thursday, May 11, 2017 11:30 a.m. CDT. For more information about the SCAI 2017 Scientific Sessions, visit http://www. . The Society for Cardiovascular Angiography and Interventions is a 4,300-member professional organization representing invasive and interventional cardiologists in approximately 70 nations. SCAI's mission is to promote excellence in invasive/interventional cardiovascular medicine through physician education and representation, and advancement of quality standards to enhance patient care. SCAI's public education program, Seconds Count, offers comprehensive information about cardiovascular disease. For more information about SCAI and Seconds Count, visit http://www. or http://www. . Follow @SCAI on Twitter for the latest heart health news.


News Article | May 10, 2017
Site: www.prweb.com

Consistent with its mission to elevate trust, transparency, and integrity in reporting the results of industry-sponsored research, Medical Publishing Insights & Practices (MPIP) today announced the launch of “What Transparency Means to Me,” the latest initiative of MPIP Transparency Matters. A global educational platform and call to action, MPIP Transparency Matters features resources to improve the level of transparency for those involved in reporting the results of industry-sponsored research. “What Transparency Means to Me” will broaden the conversation around transparency in medical publications, promote best practices, and engage interested parties in this important mission. This platform creates a space for those involved in reporting research results to share their perspectives on why transparency is essential to patient care, scientific understanding, and credibility, and how it can best be achieved when disclosing research results. “What Transparency Means to Me” will highlight shared responsibility and personal accountability for improving transparency by featuring quotes from authors, life-science companies, journal editors, and other interested parties, allowing them to add their voice to this important conversation. The site currently highlights quotes submitted by chief medical officers from MPIP sponsor companies, journal editors, medical writers, and biopharmaceutical company employees responsible for ensuring transparent disclosure of industry-sponsored research: “Responsibly sharing clinical trial data advances the science that is the foundation of medicine while also honoring the participants who gave of themselves to make a difference in the lives of others around the world now and in the future.” – Joanne Waldstreicher, MD, Chief Medical Officer, Johnson & Johnson “Transparency in clinical research is a philosophy that requires objectives and outcomes of studies to be clear to all, especially patients. Facilitated access to data and information is a necessary action needed to achieve this goal.” – Frank W. Rockhold, PhD, Professor of Biostatistics and Bioinformatics, Duke Clinical Research Institute, Duke University Medical Center “It’s all about the ‘chain of custody’ of the data. Transparent practices by the study sponsor, researcher, author, and publisher all contribute to the work’s credibility. Credible science advances research and improves patient care—the ultimate goal of medical research and reporting.” – James R. Cozzarin ELS, MWC™, Editor in Chief, AMWA Journal MPIP Transparency Matters is a global educational platform and call to action launched by MPIP in 2016 to raise awareness of the importance of transparency in reporting the results of industry-sponsored research and its impact on credibility. Furthermore, MPIP Transparency Matters is a resource hub where authors, life-science companies, journal editors, and other interested parties can find published MPIP research, tools, and recommendations to help improve the level of transparency when reporting the results of industry-sponsored research. In addition to “What Transparency Means to Me,” MPIP Transparency Matters includes several other components: More resources to improve transparency can be found at http://www.mpip-initiative.org. Despite significant progress achieved by industry, journals, and societies in enhancing transparency, persistent gaps exist in both perception and practice. To close these gaps, we need to continue to highlight why transparency matters and its link to credibility. Transparent, balanced, and timely reporting of clinical trial results in peer-reviewed journals fulfills an ethical obligation to trial participants and provides critical context to help physicians and their patients make informed treatment decisions. Furthermore, transparency enables accurate and objective data interpretation and validation and advances scientific understanding. Transparent reporting of clinical trial results is essential to establish credibility of the research outcomes and the study sponsor and to build patient trust. Conversely, reports of selective, biased, or unbalanced disclosure of research results or inaccurate or incomplete reporting of potential conflicts of interest or authorship disclosures undermines the credibility of the research outcomes and the sponsor. About MPIP: Medical Publishing Insights & Practices (MPIP) is a collaboration among members of the pharmaceutical industry and the International Society for Medical Publication Professionals (ISMPP) to elevate trust, transparency, and integrity in reporting the results of industry-sponsored research. Current corporate co-sponsors include Amgen, AstraZeneca, Biogen, Bristol-Myers Squibb, GlaxoSmithKline, Janssen Research & Development LLC, Merck, Pfizer, and Takeda. The vision of MPIP is to develop a culture of mutual respect, understanding, and trust between journal editors and pharmaceutical companies that will support more transparent and effective dissemination of results from industry-sponsored trials. To achieve that vision, our goals are to You may also access these links for additional information:


Fordyce C.B.,University of British Columbia | Douglas P.S.,Duke Clinical Research Institute
JACC: Cardiovascular Imaging | Year: 2017

The categories and quality of evidence documenting the value of noninvasive cardiovascular imaging have evolved substantially over the last several decades. From an initial emphasis on the diagnostic accuracy of various imaging modalities, cardiovascular imaging has matured into an outcomes-based field that now provides evidence on adverse events, safety, cost, and patient quality-of-life endpoints, and does so in the setting of large randomized trials. This review aims to highlight types of outcomes endpoints, including updating the hierarchy of evidence for diagnostic imaging as first proposed by Fryback and Thornbury, and critically reviewing their application in the current cardiovascular imaging evidence base. We describe the range of data categories generated to date for the various imaging modalities, and indicate how this provides insights into contemporary study design and future directions in cardiovascular imaging outcomes research. © 2017 American College of Cardiology Foundation


Raghu G.,University of Washington | Anstrom K.J.,Duke Clinical Research Institute | King Jr. T.E.,University of California at San Francisco | Lasky J.A.,Tulane University | Martinez F.J.,University of Michigan
New England Journal of Medicine | Year: 2012

BACKGROUND: A combination of prednisone, azathioprine, and N-acetylcysteine (NAC) has been widely used as a treatment for idiopathic pulmonary fibrosis. The safety and efficacy of this three-drug regimen is unknown. METHODS: In this randomized, double-blind, placebo-controlled trial, we assigned patients with idiopathic pulmonary fibrosis who had mild-to-moderate lung-function impairment to one of three groups - receiving a combination of prednisone, azathioprine, and NAC (combination therapy), NAC alone, or placebo - in a 1:1:1 ratio. The primary outcome was the change in longitudinal measurements of forced vital capacity during a 60-week treatment period. RESULTS: When approximately 50% of data had been collected (with 77 patients in the combination- therapy group and 78 in the placebo group), a planned interim analysis revealed that patients in the combination-therapy group, as compared with the placebo group, had an increased rate of death (8 vs. 1, P = 0.01) and hospitalization (23 vs. 7, P<0.001). These observations, coupled with no evidence of physiological or clinical benefit for combination therapy, prompted the independent data and safety monitoring board to recommend termination of the combination-therapy group at a mean follow-up of 32 weeks. Data from the ongoing comparison of the NAC-only group and the placebo group are not reported here. CONCLUSIONS: Increased risks of death and hospitalization were observed in patients with idiopathic pulmonary fibrosis who were treated with a combination of prednisone, azathioprine, and NAC, as compared with placebo. These findings provide evidence against the use of this combination in such patients. (Funded by the National Heart, Lung, and Blood Institute and the Cowlin Family Fund; ClinicalTrials.gov number, NCT00650091.) Copyright © 2012 Massachusetts Medical Society.


Martinez F.J.,University of Michigan | Martinez F.J.,New York Medical College | De Andrade J.A.,University of Alabama at Birmingham | Anstrom K.J.,Duke Clinical Research Institute | And 2 more authors.
New England Journal of Medicine | Year: 2014

BACKGROUND: Acetylcysteine has been suggested as a beneficial treatment for idiopathic pulmonary fibrosis, although data from placebo-controlled studies are lacking. METHODS: In our initial double-blind, placebo-controlled trial, we randomly assigned patients who had idiopathic pulmonary fibrosis with mild-to-moderate impairment in pulmonary function to receive a three-drug regimen of prednisone, azathioprine, and acetylcysteine; acetylcysteine alone; or placebo. The study was interrupted owing to safety concerns associated with the three-drug regimen. The trial continued as a two-group study (acetylcysteine vs. placebo) without other changes; 133 and 131 patients were enrolled in the acetylcysteine and placebo groups, respectively. The primary outcome was the change in forced vital capacity (FVC) over a 60-week period. RESULTS: At 60 weeks, there was no significant difference in the change in FVC between the acetylcysteine group and the placebo group (-0.18 liters and -0.19 liters, respectively; P = 0.77). In addition, there were no significant differences between the acetylcysteine group and the placebo group in the rates of death (4.9% vs. 2.5%, P = 0.30 by the log-rank test) or acute exacerbation (2.3% in each group, P>0.99). CONCLUSIONS: As compared with placebo, acetylcysteine offered no significant benefit with respect to the preservation of FVC in patients with idiopathic pulmonary fibrosis with mild-to-moderate impairment in lung function. Copyright © 2014 Massachusetts Medical Society.


Rao S.V.,Duke Clinical Research Institute | Bernat I.,University Hospital | Bertrand O.F.,Quebec Heart Lung Institute
European Heart Journal | Year: 2012

The adoption of transradial coronary angiography and coronary intervention is growing because of emerging data on its potential advantages over the femoral approach. As the adoption of radial procedures increases, it is important to understand the remaining challenges of both the technique and its implementation. In this review, we discuss four important issues related to transradial procedures-radial access site bleeding, radial artery injury and occlusion, radiation exposure, and implementation of a successful transradial primary percutaneous coronary intervention (PCI) programme. Although the radial artery is superficial and haemostasis can be achieved readily, access site bleeding can occur that, if left unchecked, can lead to forearm haematoma and, rarely, to compartment syndrome. Radial artery injury and occlusion are consequences of radial access, and randomized trials show that use of smaller diameter sheaths, adequate anticoagulation, and post-procedure 'patent' haemostasis reduce the risk of occlusion. The published literature demonstrates an association between transradial procedures and increased radiation exposure; therefore, reduction of radiation dosing during transradial procedures should be a priority for operators and catheterization laboratories. The potential reduction in mortality seen with transradial primary PCI must be balanced against the clinical imperative of timely reperfusion. Operators and catheterization laboratories should not begin a transradial primary PCI programme until sufficient radial experience has been gained in the elective setting. In addition, a protocol for femoral bailout should be considered to maintain door-to-reperfusion metrics. © 2012 The Author.


Naggie S.,Duke Clinical Research Institute | Naggie S.,Durham Veterans Affairs Medical Center | Sulkowski M.S.,Johns Hopkins University
Gastroenterology | Year: 2012

With the development of effective therapies against human immunodeficiency virus (HIV), hepatitis C virus (HCV) infection has become a major cause of morbidity and mortality among patients with both infections (coinfection). In addition to the high prevalence of chronic HCV, particularly among HIV-infected injection drug users, the rate of incident HIV infections is increasing among HIV-infected men who have sex with men, leading to recommendations for education and screening for HCV in this population. Liver disease is the second leading and, in some cases, a preventable cause of death among coinfected patients. Those at risk for liver disease progression are usually treated with a combination of interferon (IFN) and ribavirin (RBV), which is not highly effective; it has low rates of sustained virologic response (SVR), especially for coinfected patients with HCV genotype 1 and those of African descent. Direct-acting antivirals might overcome factors such as immunodeficiency that can reduce the efficacy of IFN. However, for now it remains challenging to treat coinfected patients due to interactions among drugs, additive drug toxicities, and the continued need for combination therapies that include pegylated IFN. Recently developed HCV protease inhibitors such as telaprevir and boceprevir, given in combination with pegylated IFN and RBV, could increase the rate of SVR with manageable toxicity and drug interactions. We review the latest developments and obstacles to treating coinfected patients. © 2012 AGA Institute.


Chastain C.A.,Vanderbilt University | Naggie S.,Duke Clinical Research Institute
Current HIV/AIDS Reports | Year: 2013

Hepatitis C (HCV) coinfection is the leading cause of liver-related morbidity and is a leading cause of mortality in human immunodeficiency virus (HIV)-infected individuals in the antiretroviral therapy era. Direct-acting antiviral (DAA) therapies are transforming how HCV is treated with significant improvements in efficacy and tolerability. In this article, DAA agents expected to be available in 2014 are reviewed, including telaprevir, boceprevir, sofosbuvir, simeprevir, faldaprevir, and daclatasvir. Available data regarding clinical efficacy, adverse effects, and drug interactions in HIV-HCV coinfection are discussed. The management of adverse effects of HCV therapy and treatment considerations in patients with cirrhosis are also reviewed. © 2013 Springer Science+Business Media New York.


Hess C.N.,Duke Clinical Research Institute
Journal of the American Heart Association | Year: 2014

Data regarding sex-based outcomes after percutaneous coronary intervention (PCI) for myocardial infarction are mixed. We sought to examine whether sex differences in outcomes exist in contemporary practice. We examined acute myocardial infarction patients undergoing PCI between April 2010 and October 2012 at 210 US hospitals participating in the Treatment with Adenosine Diphosphate Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events after Acute Coronary Syndrome (TRANSLATE-ACS) observational study. Outcomes included 1-year risk of major adverse cardiac events and bleeding according to Global Utilization of Strategies To Open Occluded Arteries (GUSTO) and Bleeding Academic Research Consortium (BARC) definitions. Among 6218 patients, 27.5% (n=1712) were female. Compared with men, women were older, had more comorbidities, and had lower functional status. Use of multivessel PCI and drug-eluting stents was similar between sexes, while women received less prasugrel. Unadjusted cumulative incidence of 1-year major adverse cardiac events was higher for women than for men (15.7% versus 13.6%, P=0.02), but female sex was no longer associated with higher incidence of major adverse cardiac events after multivariable adjustment (hazard ratio 0.98, 95% CI 0.83 to 1.15). Female sex was associated with higher risks of post-PCI GUSTO bleeding (9.1% versus 5.7%, P<0.0001) and postdischarge BARC bleeding (39.6% versus 27.9%, P<0.0001). Differences persisted after adjustment (GUSTO: hazard ratio 1.32, 95% CI 1.06 to 1.64; BARC: incidence rate ratio 1.42, 95% CI 1.27 to 1.56). Female and male myocardial infarction patients undergoing PCI differ regarding demographic, clinical, and treatment profiles. These differences appear to explain the higher observed major adverse cardiac event rate but not higher adjusted bleeding risk for women versus men.

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