ESCAPE Mechanistic Substudies - Ancillary to ESCAPE
Condition: Cardiovascular Diseases; Heart Diseases; Heart Failure; Heart Failure, Congestive
MeSH terms: Heart Failure; Cardiovascular Diseases; Heart Diseases
Study type: Observational

Summary: 
      To determine the value of serum markers as surrogate endpoints and hemodynamic biomarkers of
      congestive heart failure.
    

Detailed description: 
      BACKGROUND:

      The study will develop easily obtained surrogate markers to be incorporated into a model that
      can function in place of "hard" end-points in the assessment of new treatments in patients
      with heart failure. In view of the epidemiologic importance of heart failure and the large
      and expensive studies currently required to test new treatments, a successful surrogate
      marker model would be a major advance in this field that would both speed the development and
      reduce the cost of therapeutic advances.

      The study is ancillary to the NHLBI-supported clinical trial "Evaluation Study of Congestive
      Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE)." ESCAPE compares
      the efficacy of Pulmonary Artery Catheterization (PAC)-directed treatment strategy to a
      non-invasive treatment strategy on morbidity and mortality in patients with severe, class IV
      New York Heart Association (NYHA) congestive heart failure. A secondary objective of ESCAPE
      is to determine costs and resource utilization of PAC-directed treatment strategy compared to
      non-invasive treatment strategy.

      The study is in response to an initiative "Ancillary Studies in Heart, Lung, and Blood
      Disease Trials" released by the National Heart, Lung, and Blood Institute in June 2000.

      DESIGN NARRATIVE:

      The ancillary, prospective, observational study is designed to evaluate the potential of the
      serum biomarkers atrial natriuretic peptide, brain natriuretic peptide, and cardiac troponins
      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 outcomes. The
      investigators 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. They will evaluate the ability of serum
      biomarkers to serve as objective measures of both clinical and hemodynamic status and will
      assess the potential of these markers to serve as tools to assist with the selection and
      titration of therapies. In addition. they 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, the investigators 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, they 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, one
      month, and six months as a secondary endpoint of the trial. Catecholamines are also being
      collected at baseline and three 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.

      The study completion date listed in this record was obtained from the "End Date" entered in
      the Protocol Registration and Results System (PRS) record.
    

Time perspective: Retrospective