The Rationale for an Acute Heart Failure Syndromes Clinical Trials Network

Collins, Sean P.; Levy, Phillip D.; Lindsell, Christopher J.; Pang, Peter S.; Storrow, Alan B.; Miller, Chadwick D.; Naftilan, Allen J.; Thohan, Vinay; Abraham, William T.; Hiestand, Brian; Filippatos, Gerasimos; Diercks, Deborah B.; Hollander, Judd; Nowak, Richard; Peacock, W. Frank; Gheorghiade, Mihai

doi:10.1016/j.cardfail.2008.12.013

« Previous Next »Journal of Cardiac Failure
Volume 15, Issue 6 , Pages 467-474, August 2009

The Rationale for an Acute Heart Failure Syndromes Clinical Trials Network

Sean P. Collins, MD, MSc
- University of Cincinnati, Cincinnati, OH
- Correspondence to: Sean P. Collins, MD, MSc, University of Cincinnati College of Medicine, Department of Emergency Medicine, 231 Albert Sabin Way, Cincinnati, OH 45267-0769.
Phillip D. Levy, MD, MPH
- Wayne State University, Detroit, MI
Christopher J. Lindsell, PhD
- University of Cincinnati, Cincinnati, OH
Peter S. Pang, MD
- Northwestern University, Chicago, IL
Alan B. Storrow, MD
- Vanderbilt University, Nashville, TN
Chadwick D. Miller, MD
- Wake Forest University, Winston-Salem, NC
Allen J. Naftilan, MD, PhD
- Vanderbilt University, Nashville, TN
Vinay Thohan, MD
- Wake Forest University, Winston-Salem, NC
William T. Abraham, MD
- Ohio State University, Columbus, OH
Brian Hiestand, MD, MPH
- Ohio State University, Columbus, OH
Gerasimos Filippatos, MD
- Evangelismos Hospital, Athens, Greece
Deborah B. Diercks, MD
- University of California-Davis, Sacramento, CA
Judd Hollander, MD
- University of Pennsylvania, Philadelphia, PA
Richard Nowak, MD
- Henry Ford Hospital, Detroit, MI
W. Frank Peacock, MD
- The Cleveland Clinic, Cleveland, OH
Mihai Gheorghiade, MD
- Northwestern University, Chicago, IL

Received 4 September 2007; received in revised form 21 October 2008; accepted 22 December 2008. published online 11 February 2009.

Abstract

Background

Clinical trials involving novel therapies treating acute heart failure syndromes (AHFS) have shown limited success with regard to both efficacy and safety. As a direct result, outcomes have changed little over time and AHFS remains a disease process associated with largely no change in hospitalization rates (80%), hospital length of stay (median 4.5 days), and in-hospital (4-7%) and 60-day mortality (10%). Despite extensive emergency department (ED) involvement during the initial phase of AHFS management, clinical trials have enrolled patients after the ED phase of management, up to 48hours after initial therapy, long after many patients have experienced significant beneficial effects of standard therapy. As standard therapy has provided symptomatic improvement in up to 70% of patients in these trials, it is not surprising that investigational agents started after 24 to 48hours of standard therapy have shown limited clinical efficacy when compared with standard therapy.

Methods and Results

The ability to screen, enroll, and randomize in the emergency setting is fundamental. The unique environment, the ethical complexities of enrollment in emergency-based research, and the need for rapid and standardized study-compliant care represent key challenges to active recruitment in AHFS studies. Specifically, the ability to identify and enroll a large cohort of AHFS patients early (<6hours) in their presentation has been cited as the primary barrier to the appropriate design of clinical trials that includes this early window.

Conclusions

In response, we have created a network of dedicated academic physicians with experience in clinical trials and acute management of heart failure who together can surmount this barrier and provide a framework for conducting early trials in AHFS.

Key Words: Acute heart failure syndromes, clinical trials network, emergency department, cardiology