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Surrogate endpoints

Anika Wranke, Beatriz Calle Serrano, Benjamin Heidrich, Janina Kirschner, Birgit Bremer, Patrick Lehmann, Svenja Hardtke, Katja Deterding, Kerstin Port, Max Westphal, Michael P Manns, Markus Cornberg, Heiner Wedemeyer
BACKGROUND: Hepatitis delta is the most severe form of viral hepatitis. Pegylated interferon alfa (PEG- IFNα) is effective in only 25-30% of patients and is associated with frequent side effects. The aim of this study was to analyze the clinical long-term outcome of hepatitis delta in relation to different antiviral treatment strategies. METHODS: We studied 136 anti-HDV-positive patients who were followed for at least 6 months in a retrospective single-center cohort (mean time of follow up 5...
October 22, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
W Liu, J B Li, T Wang, L Bian, S H Zhang, H Q Zhang, J M Zhou, S T Song, Z F Jiang
Objective: To analyze the predict values of pathologic complete response (pCR) rates for patient outcome according to breast cancer (BC) molecular subtypes. Methods: Four hundred and sixteen patients with confirmed BC who received neoadjuvant chemotherapy (NCT) in The Affiliated Hospital of Military Medical Science Academy of the PLA were enrolled.The clinical and pathological characteristics of patients were collected. The primary endpoint was pCR rate and the secondary endpoint was disease free survival (DFS)...
September 27, 2016: Zhonghua Yi Xue za Zhi [Chinese medical journal]
Rashid Sayyid, Andrew Evans, Karen Hersey, Ranjena Maloni, Antonio Hurtado-Coll, Girish Kulkarni, Antonio Finelli, Alexandre R Zlotta, Robert Hamilton, Martin Gleave, Neil Fleshner
PURPOSE: Degarelix, a new GnRH receptor antagonist with demonstrated efficacy as first-line treatment in the management of high-risk prostate cancer, possesses some theoretical advantages over LHRH analogues in terms of avoiding "testosterone flare" and lower FSH levels. We set out to determine if pre-operative degarelix influenced surrogates of disease control in a randomized phase II study. EXPERIMENTAL DESIGN: 39 patients were randomly assigned to one of 3 different neo-adjuvant arms: degarelix only, degarelix/bicalutmaide, or LHRH agonist/bicalutamide...
October 18, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Elina Varis, Ville Pettilä, Meri Poukkanen, Stephan M Jakob, Sari Karlsson, Anders Perner, Jukka Takala, Erika Wilkman
Hyperlactatemia predicts mortality in patients with sepsis and septic shock, and its normalization is a potential treatment goal. We investigated the association of blood lactate and its changes over time with 90-day mortality in septic shock. We performed a post hoc analysis of 513 septic shock patients with admission blood lactate measurements in the prospective, observational, multicenter FINNAKI study. Repetitive lactate measurements were available in 496 patients for analyses of change in lactate values during ICU stay...
October 17, 2016: Shock
Stephen J Greene, Gregg C Fonarow, Scott D Solomon, Haris P Subacius, Andrew P Ambrosy, Muthiah Vaduganathan, Aldo P Maggioni, Michael Böhm, Eldrin F Lewis, Faiez Zannad, Javed Butler, Mihai Gheorghiade
AIMS: Change in NT-proBNP level is a common surrogate endpoint in early phase heart failure (HF) trials, but whether this endpoint is influenced by atrial fibrillation/flutter (AFF) is unclear. METHODS AND RESULTS: This analysis included 1358 patients from the ASTRONAUT trial, which randomized patients hospitalized for HF with EF ≤40% to aliskiren or placebo in addition to standard care. Patients were stratified by presence of AFF on baseline ECG. NT-proBNP was measured longitudinally by a core laboratory at baseline, 1 month, 6 months, and 12 months...
October 17, 2016: European Journal of Heart Failure
Dae-Won Lee, Myoung-Jin Jang, Kyung-Hun Lee, Eun Ju Cho, Jeong-Hoon Lee, Su Jong Yu, Yoon Jun Kim, Jung-Hwan Yoon, Tae-Yong Kim, Sae-Won Han, Do-Youn Oh, Seock-Ah Im, Tae-You Kim
BACKGROUND: Time to progression (TTP) is suggested as a reliable endpoint compared with the progression-free survival in the clinical trials of hepatocellular carcinoma (HCC). However, the correlation between TTP and overall survival (OS) has never been studied. METHODS: We searched PubMed and Embase data to obtain data source. Eligible studies were randomised controlled phase III trials, which evaluated the efficacy of systemic chemotherapy or molecular targeted therapy in advanced HCC...
October 13, 2016: British Journal of Cancer
Norbert J Tripolt, Felix Aberer, Regina Riedl, Barbara Hutz, Jasmin Url, Gudrun Dimsity, Andreas Meinitzer, Tatjana Stojakovic, Ronald Hödl, Marianne Brodmann, Franz Hafner, Harald Sourij
BACKGROUND: Patients with type 2 diabetes (T2DM) are at increased risk for macrovascular events as well as for microvascular complications. There is evidence that in patients with coronary artery disease (CAD), about 35 % suffer from manifest T2DM. Early glucose-lowering intervention in subjects with T2DM has been demonstrated to be beneficial in terms of cardiovascular risk reduction. But thus far, no data are available regarding investigating the impact of linagliptin treatment in patients with early diabetes on cardiovascular endpoints or surrogate parameters...
October 13, 2016: Trials
Luke Miller, Jason A Ferreira, Calvin Tucker
BACKGROUND: The development of novel oral anticoagulants (NOACs) has revolutionized oral anticoagulation. Rapid incorporation of NOACs into general practice has heightened the demand for directed reversal agents. Idarucizumab is a targeted reversal agent that is approved for the urgent reversal of the anticoagulant effects of dabigatran. While it is a welcome addition to reversal strategies of dabigatran, a number of clinical questions exist regarding its place in therapy. OBJECTIVE: We describe controversies regarding the use of idarucizumab therapy in patients with dabigatran-associated bleeding...
October 8, 2016: Journal of Emergency Medicine
L J Niedernhofer, J L Kirkland, W Ladiges
The first clinical trial aimed at targeting fundamental processes of aging will soon be launched (TAME: Targeting Aging with Metformin). In its wake is a robust pipeline of therapeutic interventions that have been demonstrated to extend lifespan or healthspan of preclinical models, including rapalogs, antioxidants, anti-inflammatory agents, and senolytics. This ensures that if the TAME trial is successful, numerous additional clinical trials are apt to follow. But a significant impediment to these trials remains the question of what endpoints should be measured? The design of the TAME trial very cleverly skirts around this based on the fact that there are decades of data on metformin in humans, providing unequaled clarity of what endpoints are most likely to yield a positive outcome...
October 6, 2016: Ageing Research Reviews
Philipp Uhl, Lea A Franke, Christina Rehberg, Claudia Wollmann, Peter Stahlschmidt, Lukas Jeker, Carsten A Brühl
Wild and domesticated bee species are exposed to a variety of pesticides which may drive pollinator decline. Due to wild bee sensitivity data shortage, it is unclear if the honey bee Apis mellifera is a suitable surrogate species in the current EU risk assessment scheme. Furthermore, the underlying causes for sensitivity differences in bees are not established. We assessed the acute toxicity (median lethal dose, LD50) of dimethoate towards multiple bee species, generated a species sensitivity distribution and derived a hazardous dose (HD5)...
September 30, 2016: Scientific Reports
Dominic Chow, Cecilia Shikuma, Corey Ritchings, Muxing Guo, Lisa Rosenblatt
INTRODUCTION: Patients with human immunodeficiency virus (HIV) infection have an increased risk of cardiovascular disease (CVD). While viral suppression with antiretroviral therapy decreases CVD risk overall, several studies have suggested that certain antiretrovirals, particularly certain protease inhibitors, may be associated with an increased relative risk of CVD. In AIDS Clinical Trials Group 5260 s, ritonavir-boosted atazanavir (ATV) was associated with slower atherosclerosis progression compared to ritonavir-boosted darunavir and raltegravir, potentially due to hyperbilirubinemia...
September 27, 2016: Infectious Diseases and Therapy
Adel Boueiz, Sharon M Lutz, Michael H Cho, Craig P Hersh, Russell P Bowler, George R Washko, Eitan Halper-Stromberg, Per Bakke, Amund Gulsvik, Nan M Laird, Terri H Beaty, Harvey O Coxson, James D Crapo, Edwin K Silverman, Peter J Castaldi, Dawn L DeMeo
RATIONALE: Emphysema has considerable variability in the severity and distribution of parenchymal destruction throughout the lungs. Upper lobe predominant emphysema has emerged as an important predictor of response to lung volume reduction surgery. Yet, aside from alpha-1 antitrypsin deficiency, the genetic determinants of emphysema distribution remain largely unknown. OBJECTIVES: To identify the genetic influences of emphysema distribution in non-alpha-1 antitrypsin deficient smokers...
September 26, 2016: American Journal of Respiratory and Critical Care Medicine
Kunihiro Matsushita, Jingsha Chen, Yingying Sang, Shoshana H Ballew, Ryutaro Shimazaki, Masafumi Fukagawa, Enyu Imai, Josef Coresh, Akira Hishida
Predominantly based on North American and European studies, 30% to 40% declines in estimated glomerular filtration rate (eGFR) over a few years are strongly associated with the risk of end-stage renal disease (ESRD) and have been proposed as surrogate endpoints of ESRD for clinical research. However, this association has not been systematically quantified in Asian populations. To do this we studied adult Japanese patients with baseline eGFR 10-59 ml/min/1.73m(2). Changes in eGFR from baseline measured by centrally assessed serum creatinine were linked to subsequent ESRD in 2410 patients after one year and in 2079 patients after year 2...
November 2016: Kidney International
Martin R Cowie
The majority of patients with heart failure have sleep-disordered breathing (SDB)-with central (rather than obstructive) sleep apnoea becoming the predominant form in those with more severe disease. Cyclical apnoeas and hypopnoeas are associated with sleep disturbance, hypoxaemia, haemodynamic changes, and sympathetic activation. Such patients have a worse prognosis than those without SDB. Mask-based therapies of positive airway pressure targeted at SDB can improve measures of sleep quality and partially normalise the sleep and respiratory physiology, but recent randomised trials of cardiovascular outcomes in central sleep apnoea have been neutral or suggested the possibility of harm, likely from increased sudden death...
September 17, 2016: Current Heart Failure Reports
Fleur M van der Valk, Simone L Verweij, Koos A H Zwinderman, Aart C Strang, Yannick Kaiser, Henk A Marquering, Aart J Nederveen, Erik S G Stroes, Hein J Verberne, James H F Rudd
OBJECTIVES: This study assessed 5 frequently applied arterial (18)fluorodeoxyglucose ((18)F-FDG) uptake metrics in healthy control subjects, those with risk factors and patients with cardiovascular disease (CVD), to derive uptake thresholds in each subject group. Additionally, we tested the reproducibility of these measures and produced recommended sample sizes for interventional drug studies. BACKGROUND: (18)F-FDG positron emission tomography (PET) can identify plaque inflammation as a surrogate endpoint for vascular interventional drug trials...
October 2016: JACC. Cardiovascular Imaging
R Loch Macdonald, Tom A Schweizer
Subarachnoid haemorrhage is an uncommon and severe subtype of stroke affecting patients at a mean age of 55 years, leading to loss of many years of productive life. The rupture of an intracranial aneurysm is the underlining cause in 85% of cases. Survival from aneurysmal subarachnoid haemorrhage has increased by 17% in the past few decades, probably because of better diagnosis, early aneurysm repair, prescription of nimodipine, and advanced intensive care support. Nevertheless, survivors commonly have cognitive impairments, which in turn affect patients' daily functionality, working capacity, and quality of life...
September 13, 2016: Lancet
Ippei Fukada, Kazuhiro Araki, Kokoro Kobayashi, Tomoko Shibayama, Shunji Takahashi, Rie Horii, Futoshi Akiyama, Takuji Iwase, Shinji Ohno, Kiyohiko Hatake, Yasuo Hozumi, Naohiro Sata, Yoshinori Ito
BACKGROUND: Pathological complete response (pCR) with neoadjuvant chemotherapy (NAC) has been regarded as a surrogate endpoint for disease-free survival (DFS) and overall survival (OS) of patients with breast cancer. No consensus regarding the definition of pCR has been established; there are several definitions according to a variety of classifications. Eradication of cancer cells in both breast and lymph nodes has been better associated with improved prognosis than in the breast alone...
2016: PloS One
Pedram Hamrah, Yashar Seyed-Razavi, Takefumi Yamaguchi
Corneal immunoimaging and neuroimaging approaches facilitate in vivo analyses of the cornea, including high-resolution imaging of corneal immune cells and nerves. This approach facilitates the analyses of underlying immune and nerve alterations not detected by clinical slit-lamp examination alone. In this review, we describe recent work performed in our translational ocular immunology center with a focus on "bench-to-bedside" and "bedside-to-bench" research. The ability to visualize dendritiform immune cells (DCs) in patients with laser in vivo confocal microscopy (IVCM), recently discovered in the central murine cornea, has allowed us to demonstrate their utility as a potential surrogate biomarker for inflammatory ocular surface diseases...
November 2016: Cornea
Phaik Yeong Cheah, Michael Parker, Arjen M Dondorp
Over 90% of deaths attributable to malaria are in African children under 5 years old. Yet, new treatments are often tested primarily in adult patients and extrapolations have proven to be sometimes invalid, especially in dosing regimens. For studies in severe malaria an additional complication is that the decline in severe malaria in adult patients precludes sufficiently powered trials in adults, before the intervention can be tested in the ultimate target group, paediatric severe malaria. In this paper we propose an alternative pathway to the development of drugs for use in paediatric severe malaria...
September 2016: International Health
Atsushi Tanaka, Toyoaki Murohara, Isao Taguchi, Kazuo Eguchi, Makoto Suzuki, Masafumi Kitakaze, Yasunori Sato, Tomoko Ishizu, Yukihito Higashi, Hirotsugu Yamada, Mamoru Nanasato, Michio Shimabukuro, Hiroki Teragawa, Shinichiro Ueda, Satoshi Kodera, Munehide Matsuhisa, Toshiaki Kadokami, Kazuomi Kario, Yoshihiko Nishio, Teruo Inoue, Koji Maemura, Jun-Ichi Oyama, Mitsuru Ohishi, Masataka Sata, Hirofumi Tomiyama, Koichi Node
BACKGROUND: Type 2 diabetes mellitus is associated strongly with an increased risk of micro- and macro-vascular complications, leading to impaired quality of life and shortened life expectancy. In addition to appropriate glycemic control, multi-factorial intervention for a wide range of risk factors, such as hypertension and dyslipidemia, is crucial for management of diabetes. A recent cardiovascular outcome trial in diabetes patients with higher cardiovascular risk demonstrated that a SGLT2 inhibitor markedly reduced mortality, but not macro-vascular events...
2016: Cardiovascular Diabetology
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