Elsevier

American Heart Journal

Volume 153, Issue 2, February 2007, Pages 201-211
American Heart Journal

Trial Design
Heart Failure and A Controlled Trial Investigating Outcomes of Exercise TraiNing (HF-ACTION): Design and rationale

https://doi.org/10.1016/j.ahj.2006.11.007Get rights and content

Background

Although there are limited clinical data to support the use of exercise training as a means to reduce mortality and morbidity in patients with heart failure, current guidelines state that exercise is beneficial.

Trial Design

The objective of this trial is to determine whether exercise training reduces all-cause mortality or all-cause hospitalization for patients with left ventricular systolic dysfunction and heart failure symptoms. After undergoing baseline assessments to determine whether they can safely exercise, patients are randomized to either usual care or exercise training. Patients in the exercise training arm attend 36 supervised facility-based exercise training sessions. Exercise modalities are cycling or walking. After completing 18 sessions, patients initiate home-based exercise and then transition to solely home-based exercise after completing all 36 sessions. Patients return for facility-based training every 3 months to reinforce their exercise training program. Patients are followed for up to 4 years. Physiologic, quality-of-life, and economic end points that characterize the effect of exercise training in this patient population will be measured at baseline and at intervals throughout the trial. Blood samples will be collected to examine biomarkers such as brain natriuretic peptide, tumor necrosis factor, and C-reactive protein.

Conclusions

Because of its relatively low cost, high availability, and ease of use, exercise training is an intervention that could be accessible to most patients with heart failure. The HF-ACTION trial is designed to definitively assess the effect of exercise training on the clinically relevant end points of mortality, hospitalization, and quality of life in patients with heart failure.

Section snippets

Methods

The primary objective of the HF-ACTION trial is to test the hypothesis that patients with LV systolic dysfunction and New York Heart Association (NYHA) classes II to IV heart failure symptoms who undertake exercise training in addition to usual care will have a 20% reduction in the composite end point of all-cause mortality and all-cause hospitalization over 2 years as compared with patients who receive usual care only.

Each component of the primary end point—mortality and

Trial organization

The HF-ACTION trial incorporates the general organizational features of phase 3 therapeutic clinical trials with additional features that address the unique nature of the intervention (Figure 1). The organization includes (1) a steering committee, (2) an executive committee, (3) a coordinating center, (4) regional centers, and (5) a DSMB. Working with the coordinating center are 4 core laboratories: (1) CPX testing core laboratory; (2) echocardiography core laboratory; (3) exercise training

Discussion

The HF-ACTION trial is the largest randomized clinical trial of exercise training ever performed. It represents a critical step in establishing exercise as a therapy for patients with LV dysfunction. The patient population enrolled in this trial will be broadly representative of patients with heart failure, including large numbers of women, individuals of ethnic minority, and individuals of low socioeconomic status. The clinical practices participating in the trial are geographically diverse

Conclusions

The high morbidity and mortality as well as the persistent exercise intolerance that occurs in patients with heart failure who have systolic dysfunction, despite optimal pharmacotherapy, underscore the importance of research to evaluate novel treatment strategies, such as exercise training. The primary objective of the HF-ACTION trial is to determine the long-term safety and efficacy of exercise training in addition to standard of care versus a strategy of standard care only for patients with

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    • Cited by (0)

    The HF-ACTION trial is funded by 13 grants (Coordinating center/C. O'Connor, Principal Investigator: 5U01-HL063747; Economic and Quality of Life/K. Schulman, Principal Investigator: 5U01-HL066461; U grant enrolling centers—Boston Medical Center/W. Colucci, Principal Investigator: HL068973; Case Western Reserve University/I. Piña, Principal Investigator: HL066501; Emory University/A. Smith, Principal Investigator: HL066482; Henry Ford Hospital/S. Keteyian, Principal Investigator: HL064250; Ohio State University/W. Abraham, Principal Investigator: HL066494; Oregon Health Science University/R. Hershberger, Principal Investigator: HL064257; University of Alabama/V. Bittner, Principal Investigator: HL066497; University of California–Los Angeles/G. Fonarow, Principal Investigator: HL068980; University of Colorado/E. Wolfel, Principal Investigator: HL064265; Wake Forest University/D. Kitzman, Principal Investigator: HL066491; Washington University of St Louis/G. Ewald, Principal Investigator: HL064264) from the National Heart, Lung, and Blood Institute (Bethesda, Md).

    Clinicaltrials.gov%20no. NCT00047437.

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