ESCAPE Mechanistic Substudies

Duke University, Durham NC

Investigators

Linked publications & trials

Abstract

DESCRIPTION (Applicant's Abstract) This proposal is a prospective, observational study designed to evaluate the potential of serum biomarkers to serve both as prognostic indices and as surrogate endpoints for death and hospitalization in heart failure trials. The first goal wlll be accomplished by evaluating relations between levels of natriuretic peptides, troponins, and clinical outcomes. We will develop a risk score for patients with advanced heart failure that incorporates the serum biomarkers and clinical variables and test for interactions between this score and pulmonary artery catheterization. We will also evaluate the ability of serum biomarkers to serve as objective measures of both clinical and hemodynamic status and assess the potential of these markers to serve as tools to assist with the selection and titration of therapies. In addition. we will examine the relations between levels of natriuretic peptides, troponins, and catecholamines. This information will be the launching point for the second goal, which will be to examine the relationship between the serum biomarkers and the treatment effect of pulmonary-artery catheterization on death and hospitalization. In addition, we will evaluate the relations between levels of natriuretic peptides, troponins, and the treatment effects of B-adrenergic antagonists and inotropic agents on clinical outcomes. Ultimately, we intend to construct a statistical model that incorporates the serum biomarkers with greatest promise and clinical variables demonstrated to predict survival. This final model may prove to be the best Surrogate endpoint possible, as it will capture an array of physiological mechanisms through which pulmonary-artery catheter guided therapy may have an effect. This proposed substudy will be conducted within the framework of the ESCAPE trial. Natriuretic peptide levels are currently being collected at randomization, discharge, 1 month, and 6 months as a secondary endpoint of the trial. Catecholamines are also being collected at baseline and 3 months. In addition, the ESCAPE investigators are all ready capturing detailed demographic, clinical, and physiological information as part of the protocol for the primary study.