Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

End points for clinical trials in acute heart failure syndromes.

ABSTRACT: Acute heart failure syndromes (AHFS) remain a major cause of morbidity and mortality, in part because the development of new therapies for these disorders has been marked by frequent failure and little success. The heterogeneity of current approaches to AHFS drug development, particularly with regard to end points, remains a major potential barrier to progress in the field. End points involving hemodynamic status, biomarkers, symptoms, hospital stay, end organ function, and mortality have all been employed either alone or in combination in recent randomized clinical trials in AHFS. In this review, we will discuss the various end point domains from both a clinical and a statistical perspective, summarize the wide variety of end points used in completed and ongoing AHFS studies, and suggest steps for greater standardization of end points across AHFS trials.

SUBMITTER: Allen LA

PROVIDER: S-EPMC3961583 | biostudies-other | 2009 Jun

REPOSITORIES: biostudies-other

ACCESS DATA

Json Xml

Publications

End points for clinical trials in acute heart failure syndromes.

Allen Larry A LA Hernandez Adrian F AF O'Connor Christopher M CM Felker G Michael GM

Journal of the American College of Cardiology 20090601 24

Acute heart failure syndromes (AHFS) remain a major cause of morbidity and mortality, in part because the development of new therapies for these disorders has been marked by frequent failure and little success. The heterogeneity of current approaches to AHFS drug development, particularly with regard to end points, remains a major potential barrier to progress in the field. End points involving hemodynamic status, biomarkers, symptoms, hospital stay, end organ function, and mortality have all be ...[more]

PMID: 19520247

Similar Datasets

Insulin therapy in acute coronary syndromes: an appraisal of completed and ongoing randomised trials with important clinical end points.

Project description:Insulin therapy was first proposed as an adjunctive therapy in patients with acute coronary syndromes (ACS) in the 1960s. Since then, numerous randomised clinical trials have been conducted to determine the efficacy and to define the role of insulin therapy in ACS. This review will discuss: 1) completed trials of insulin therapy in ACS, including both glucose-insulin-potassium (GIK) approaches and non-GIK approaches; 2) trials of insulin therapy in critically ill non-ACS patients and the lessons from these trials that can be applied to trials of insulin in ACS patients; and 3) a summary of ongoing and planned trials of insulin in ACS patients.

| S-EPMC3746495 | biostudies-other

NT-proBNP Qualifies as a Surrogate for Clinical End Points in Heart Failure.

Project description:N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a well-established biomarker in heart failure (HF) but controversially discussed as a potential surrogate marker in HF trials. We analyzed the NT-proBNP/mortality relationship in real-world data (RWD) of 108,330 HF patients from the IBM Watson Health Explorys database and compared it with the NT-proBNP / clinical event end-point relationship in 20 clinical HF studies. With a hierarchical statistical model, we quantified the functional relationship and interstudy variability. To independently qualify the model, we predicted outcome hazard ratios in five phase III HF studies solely based on NT-proBNP measured early in the respective study. In RWD and clinical studies, the relationship between NT-proBNP and clinical outcome is well described by an Emax model. The NT-proBNP independent baseline risk (R0 , RWD/studies median (interstudy interquartile range): 5.5%/3.0% (1.7-4.9%)) is very low compared with the potential NT-proBNP-associated maximum risk (Rmax : 55.2%/79.4% (61.5-89.0%)). The NT-proBNP concentration associated with the half-maximal risk is comparable in RWD and across clinical studies (EC50 : 3,880/2,414 pg/mL (1,460-4,355 pg/mL)). Model-based predictions of phase III outcomes, relying on short-term NT-proBNP data only, match final trial results with comparable confidence intervals. Our analysis qualifies NT-proBNP as a surrogate for clinical outcome in HF trials. NT-proBNP levels after short treatment durations of less than 10 weeks quantitatively predict hazard ratios with confidence levels comparable to final trial readout. Early NT-proBNP measurement can therefore enable shorter and smaller but still reliable HF trials.

| S-EPMC8360001 | biostudies-literature

Validity of composite end points in clinical trials.

Project description: Not available

| S-EPMC554039 | biostudies-literature

Real-Life Multimarker Monitoring in Patients with Heart Failure: Continuous Remote Monitoring of Mobility and Patient-Reported Outcomes as Digital End Points in Future Heart-Failure Trials.

Project description:AimsHeart failure (HF) affects approximately 26 million people worldwide. With an aging global population, innovative approaches to HF evaluation and management are needed to cope with the worsening HF epidemic. The aim of the Real-Life Multimarker Monitoring in Patients with Heart Failure (REALIsM-HF) study (NCT03507439) is to evaluate a composite instrument comprising remote, real-time, activity-monitoring devices combined with daily electronic patient-reported outcome (ePRO) items in patients who have been hospitalized for HF and are undergoing standard HF assessment (e.g., 6-min walking distance [6MWD], blood biomarkers, Kansas City Cardiomyopathy Questionnaire [KCCQ], and echocardiography).MethodsREALIsM-HF is an ongoing, 12-week, observational study enrolling 80-100 patients aged ≥45 years with HF with preserved ejection fraction (HFpEF; EF ≥45%) or reduced EF (HFrEF; EF ≤35%). Statistical analyses will include examining the association between data from wearables (the AVIVO© mobile patient management patch or VitalPatch© biosensor, and the DynaPort MoveMonitor©), daily ePROs, and conventional HF metrics (e.g., serum/plasma biomarkers, 6MWD, KCCQ, and echocardiographic parameters). The feasibility of and patient compliance with at-home devices will be documented, and the data captured for the purpose of establishing reference values in patients with HFpEF or HFrEF will be summarized.ConclusionsThe REALIsM-HF study is to evaluate the longitudinal daily activity profiles of patients with HF and correlate these with changes in serum/plasma biomarker profiles, symptoms, quality of life, and cardiac function and morphology to inform the use of wearable activity monitors for developing novel therapies and managing patients.

| S-EPMC7548956 | biostudies-literature

Reassessing the Role of Surrogate End Points in Drug Development for Heart Failure.

Project description:With few notable exceptions, drug development for heart failure (HF) has become progressively more challenging, and there remain no definitively proven therapies for patients with acute HF or HF with preserved ejection fraction. Inspection of temporal trends suggests an increasing rate of disagreement between early-phase and phase III trial end points. Preliminary results from phase II HF trials are frequently promising, but increasingly followed by disappointing phase III results. Given this potential disconnect, it is reasonable to carefully re-evaluate the purpose, design, and execution of phase II HF trials, with particular attention directed toward the surrogate end points commonly used by these studies. In this review, we offer a critical reappraisal of the role of phase II HF trials and surrogate end points, highlighting challenges in their use and interpretation, lessons learned from past experiences, and specific strengths and weaknesses of various surrogate outcomes. We conclude by proposing a series of approaches that should be considered for the goal of optimizing the efficiency of HF drug development. This review is based on discussions between scientists, clinical trialists, industry and government sponsors, and regulators that took place at the Cardiovascular Clinical Trialists Forum in Washington, DC, on December 2, 2016.

| S-EPMC6205720 | biostudies-literature

Novel end points for clinical trials in young children with cystic fibrosis.

Project description:Cystic fibrosis (CF) lung disease commences early in the disease progression and is the most common cause of mortality. While new CF disease-modifying agents are currently undergoing clinical trial evaluation, the implementation of such trials in young children is limited by the lack of age-appropriate clinical trial end points. Advances in infant and preschool lung function testing, imaging of the chest and the development of biochemical biomarkers have led to increased possibility of quantifying mild lung disease in young children with CF and objectively monitoring disease progression over the course of an intervention. Despite this, further standardization and development of these techniques is required to provide robust objective measures for clinical trials in this age group.

| S-EPMC5033038 | biostudies-literature

Association between Respiratory Failure and Clinical Outcomes in Patients with Acute Heart Failure: Analysis of 5 Pooled Clinical Trials.

Project description:BackgroundDespite a temporal increase in respiratory failure in patients hospitalized with acute heart failure (HF), clinical trials have largely not reported the incidence or associated clinical outcomes for patients requiring mechanical ventilation.Methods and resultsAfter pooling 5 acute HF clinical trials, we used multivariable logistic regression adjusted for demographics, comorbidities, examinations, and laboratory findings to assess associations between mechanical ventilation and clinical outcomes. Among the 8296 patients, 210 (2.5%) required mechanical ventilation. Age, sex, smoking history, baseline ejection fraction, HF etiology, and the proportion of patients randomized to treatment or placebo in the original clinical trial were similar between groups (all, P > 0.05). Baseline diabetes mellitus was more common in the mechanical ventilation group (P = 0.02), but other comorbidities, including chronic lung disease, were otherwise similar (all P > 0.05). HF rehospitalization at 30 days (12.7% vs 6.6%, P < 0.001) and all-cause 60-day mortality (33.3% vs 6.1%, P < 0.001) was higher among patients requiring mechanical ventilation. After multivariable adjustment, mechanical ventilation use was associated with an increased 30-day HF rehospitalization (odds ratio 2.03; 95% confidence interval, 1.29-3.21, P = 0.002), 30-day mortality (odds ratio 10.40; 95% confidence interval, 7.22-14.98, P < 0.001), and 60-day mortality (odds ratio 7.68; 95% confidence interval, 5.50-10.74, P < 0.001). The influence of mechanical ventilation did not differ by HF etiology or baseline ejection fraction (both, interaction P > 0.20).ConclusionsRespiratory failure during an index hospitalization for acute HF was associated with increased rehospitalization and all-cause mortality. The development of respiratory failure during an acute HF admission identifies a particularly vulnerable population, which should be identified for closer monitoring.

| S-EPMC8527461 | biostudies-literature

End points and outcomes in castration-resistant prostate cancer: from clinical trials to clinical practice.

Project description:New therapeutic approaches for castration-resistant prostate cancer (CRPC) introduce new treatment dilemmas: how best to sequence these options to maximally benefit patients, what tests to perform before and after treatment to assess disease status, and how to interpret the test results and use them to guide treatment. New and specific end points for different classes of drugs are needed to provide the information to guide these treatment decisions. In 2008, the Prostate Cancer Working Group 2 consensus criteria for early-phase clinical trials redefined clinical trial end points as first, to control, relieve, or eliminate disease manifestations present when treatment is started and second, to prevent or delay future disease manifestations. Disease manifestations include prostate-specific antigen (PSA), soft-tissue disease (nodes and/or viscera), bone disease (most common site of spread), and symptoms. Recent US Food and Drug Administration (FDA) approvals for CRPC therapies have been based on the prevent/delay end points that reflect unequivocal benefit to a patient: prolongation of life or reduction in skeletal-related events (SREs). For the practicing oncologist, the control/relieve/eliminate outcomes should serve primarily to inform the decision of whether to continue therapy. In this review, we consider individual end points such as PSA, imaging, and patient-reported outcomes in the context of the control/relieve/eliminate and prevent/delay framework. We address the time-to-event end points of metastasis prevention, SRE, time to progression, and overall survival in the context of regulatory approvals. We also discuss circulating tumor cells measured with the CellSearch assay, recently cleared by the FDA for monitoring CRPC.

| S-EPMC3675708 | biostudies-literature

Important Surgical and Clinical End Points in Neoadjuvant Immunotherapy Trials in Resectable NSCLC.

Project description:Neoadjuvant immunotherapy may improve outcomes in patients with resectable NSCLC and is being evaluated in phase 2 and 3 studies. Nevertheless, preoperative treatment postpones resection; the potential for increased surgical complexity and greater intra- and postoperative morbidity and mortality is an additional consideration. In studies primarily designed to evaluate efficacy, the impact of neoadjuvant immunotherapy on surgery is based on parameters that are poorly defined and reported differently between studies. Defining and reporting common end points among trials would improve understanding and facilitate cross-comparison of different immunotherapy regimens and may facilitate wider adoption of induction therapies by surgeons and oncologists. We propose several surgical end points and related metrics for neoadjuvant immunotherapy in resectable NSCLC. These include the periods from screening to treatment initiation and from last neoadjuvant dose to surgery; reporting of the allowable window for surgery to preclude masking delays caused by induction treatment-related toxicity; complete resection (R0) rate; preoperative downstaging; a standardized list of immune-related adverse events and associated delay to surgery; preoperative attrition; postoperative attrition before adjuvant therapy; and postoperative 30- and 90-day mortality and morbidity rates. Intraoperative end points (blood loss, duration, and type of surgery) and our proposed system of grading complexity based on lymphadenopathy and fibrosis would allow quantitation of technical difficulty and quality of oncologic resection. In conclusion, the standardization, reporting, and prospective inclusion of these end points in study protocols would provide a comparative overview of the impact of different neoadjuvant immunotherapy regimens on surgery and ultimately clinical oncologic outcomes in resectable NSCLC.

| S-EPMC8552106 | biostudies-literature

Six-month freedom from treatment failure is an important end point for acute GVHD clinical trials.

Project description:We studied the American Society for Blood and Marrow Transplantation (ASBMT) 6-month (m) freedom from treatment failure (FFTF) as a predictor of survival for patients with acute GVHD (aGVHD) requiring treatment. Adult patients undergoing allogeneic hematopoietic cell transplant (HCT) from February 2007 to March 2009 who were enrolled in a prospective biomarker clinical trial and developed aGVHD requiring systemic corticosteroids by day +100 were included (N=44). Six-month FFTF was defined as per the ASBMT guidelines (absence of death, malignancy relapse/progression or systemic immunosuppression change within 6 months of starting steroids and before chronic GVHD development). aGVHD was treated with systemic corticosteroids in 44 patients. Day 28 response after steroid initiation (complete response+very good partial response+partial response) occurred in 38 (87%) patients, but only 28 (64%) HCT recipients met the 6-m FFTF end point. Day 28 response predicted 6-m FFTF. Achieving 6-m FFTF was associated with improved 2-year (y) OS (81% vs 48%; P=0.03) and decreased 2-y non-relapse mortality (8% vs 49%; P=0.01). In multivariate analysis, 6-m FFTF continued to predict improved OS (hazard ratio, 0.27; P=0.03). The 6-m FFTF end point measures fixed outcomes, predicts long-term therapeutic success and could be less prone to measurement error than aGVHD clinical response at day 28.

| S-EPMC3946331 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data