Exercise Training Program to Improve Clinical Outcomes in Individuals With Congestive Heart Failure - Full Text View

Sponsor:	National Heart, Lung, and Blood Institute (NHLBI)
Information provided by:	National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov Identifier:	NCT00047437

Purpose

The purpose of this study is to determine the long-term safety and effectiveness of exercise training for individuals with congestive heart failure (CHF).

Condition	Intervention	Phase
Cardiovascular Diseases Heart Diseases Heart Failure, Congestive	Behavioral: Supervised Exercise Training Program	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Prevention
Official Title:	Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION)

Resource links provided by NLM:

MedlinePlus related topics: Exercise and Physical Fitness Heart Diseases Heart Failure

U.S. FDA Resources

Further study details as provided by National Heart, Lung, and Blood Institute (NHLBI):

Primary Outcome Measures:

Composite of all-cause mortality and all-cause hospitalization rates (measured at Year 3) [ Time Frame: Measured as events occur during the lifespan of the trial. ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Changes in peak VO2 [ Time Frame: Measured at 3 months, 12 months, and 24 months. ] [ Designated as safety issue: No ]
Changes in VE/VCO2 slope [ Time Frame: Measured at 3 months, 12 months, and 24 months. ] [ Designated as safety issue: No ]
Heart rate at a submaximal work load defined as the end of the exercise test's second stage [ Time Frame: Measured at 3 months, 12 months, and 24 months. ] [ Designated as safety issue: No ]
Changes in 6-minute walk (measured at Month 3 and Year 1) [ Time Frame: Measured at 3 months, 12 months, 24 months, 36 months, and at end of study. ] [ Designated as safety issue: No ]
Composite of cardiovascular mortality and cardiovascular hospitalization rates [ Time Frame: Measured as events occur during the life of the trial. ] [ Designated as safety issue: Yes ]
Composite of cardiovascular mortality and CHF hospitalization rates [ Time Frame: Measured as events occur during the life of the trial. ] [ Designated as safety issue: Yes ]
All-cause mortality rates [ Time Frame: Measured as events occur during the life of the trial. ] [ Designated as safety issue: Yes ]
Cardiovascular mortality rates [ Time Frame: Measured as events occur during the life of the trial. ] [ Designated as safety issue: Yes ]
All-cause hospitalization rates [ Time Frame: Measured as events occur during the life of the trial. ] [ Designated as safety issue: Yes ]
CHF hospitalization rates [ Time Frame: Measured as events occur during the life of the trial. ] [ Designated as safety issue: Yes ]
Heart attack rates [ Time Frame: Measured as events occur during the life of the trial. ] [ Designated as safety issue: Yes ]
Worsening CHF event rates [ Time Frame: Measured as events occur during the life of the trial. ] [ Designated as safety issue: Yes ]
Composite of all-cause mortality, all-cause hospitalization, emergency room visit, and urgent clinic visit for CHF exacerbation rates [ Time Frame: Measured as events occur during the life of the trial. ] [ Designated as safety issue: Yes ]
Cost [ Time Frame: Measured throughout the life of the trial. ] [ Designated as safety issue: No ]
Quality of life [ Time Frame: Measured at baseline, months 3, 6, 9, 12, 15, 18, 21, 24, 36, and end of study ] [ Designated as safety issue: No ]

Enrollment:	2331
Study Start Date:	April 2003
Study Completion Date:	July 2008
Primary Completion Date:	July 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: 2	Behavioral: Supervised Exercise Training Program Exercise 30 minutes minimum three times per week.
No Intervention: 1

Detailed Description:

BACKGROUND:

CHF affects approximately five million Americans and is the number one cause of hospital admission in individuals over the age of 65. Although exercise training improves several clinical measures in individuals with CHF (e.g., peak VO2, heart rate variability, and plasma norepinephrine levels), it is not known whether exercise training reduces mortality in individuals with CHF.

DESIGN NARRATIVE:

This multicenter randomized study will determine if exercise training reduces mortality and hospitalization rates in individuals with moderate to severe CHF. The secondary objective is to evaluate whether an exercise program designed for individuals with CHF improves quality of life and functioning, is economically advantageous, and prevents medical complications.

Three thousand individuals with moderate to severe CHF will be randomly assigned to either standard medical therapy and education, or standard medical therapy and education plus a supervised exercise training program. The exercise training will include 36 supervised clinic-based training sessions followed by home-based exercise and periodic supervised sessions for reinforcement. Participants assigned to the supervised exercise training program will use either a treadmill or stationary bicycle, which will be provided for them.

Recruitment Status: As of November 9, 2006, HF-ACTION has enrolled 2180 subjects and will conclude enrollment at the end of February, 2007, with an anticipated enrollment of approximately 2300 subjects.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

LVEF less than or equal to 35%
New York Heart Association (NYHA) class II, III, or IV CHF diagnosis in the 3 months prior to study entry, with a minimum of 6 weeks of treatment
Must be on optimal heart failure therapy according to American Heart Association (AHA), American College of Cardiology (ACC), and Heart Failure Society of America (HFSA) heart failure guidelines, including treatment with angiotensin II converting enzyme inhibitors (ACEI) and beta-blocker therapy, or have documentation justifying why optimal therapy is not being used, including intolerance, contraindication, participant preference, or physician's judgment
Must be on stable doses of medications (e.g., beta-blocker, ACEI, and additional medications as listed in the study guidelines) for 6 weeks prior to study entry
Must be in stable medical condition and able to begin an exercise program, as determined by study physician

Exclusion Criteria:

Comorbid disease, behavioral limitations, or other limitations that would interfere with exercise training, or would prevent completion of 1 year of exercise training
Pregnant or planning to become pregnant in the year following study entry
Major heart event or heart procedure within the 6 weeks prior to study entry
Heart procedure or hospitalization for any reason planned in the future
Expecting to receive a heart transplant in the 6 months following study entry
CHF caused by significant uncorrected primary valvular disease (except mitral regurgitation secondary to left ventricular dysfunction); if valve replacement has been performed, may not participate for 12 months following the procedure
CHF caused by congenital heart disease or obstructive cardiomyopathy
Performance of exercise training at regular intervals (more than once per week) at a moderate to vigorous intensity at any time in the 6 weeks prior to study entry
Exercise testing results that would prevent safe exercise training, as defined by the American Association of Cardiovascular and Pulmonary Rehabilitation (AACVPR) guidelines, including abnormal blood pressure response, early ischemic changes, and unexpected life-threatening arrhythmia
Use of fixed-rate pacemakers, pacemakers with inability to attain target heart rates, or automatic implantable cardioverter defibrillator (AICD) devices with heart rate limits set below the target heart rate for exercise training
Use of an intracardiac device such as an implantable cardioverter defibrillator (ICD) or a cardiac resynchronization therapy pacemaker in the 6 months prior to study entry (must demonstrate stability for 6 weeks post-procedure)
Primary physician considers placement of an intracardiac device such as an ICD or a cardiac resynchronization therapy pacemaker probable within 6 months of study entry; will be excluded until such device has been placed and 6 weeks of stabilization have passed
Participation in another clinical trial that may interfere with study participation, follow-up, or data collection, or that may affect cardiovascular morbidity or mortality

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00047437

Show 80 Study Locations

Sponsors and Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

Study Chair:	Christopher M. O'Connor	Duke University
Study Chair:	David J. Whellan	Jefferson Medical College of Thomas Jefferson University

More Information

Additional Information:

Click here for the Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training web site This link exits the ClinicalTrials.gov site

This link exits the ClinicalTrials.gov site

Publications:

Whellan DJ, O'Connor CM, Lee KL, Keteyian SJ, Cooper LS, Ellis SJ, Leifer ES, Kraus WE, Kitzman DW, Blumenthal JA, Rendall DS, Houston-Miller N, Fleg JL, Schulman KA, Pina IL; HF-ACTION Trial Investigators. Heart failure and a controlled trial investigating outcomes of exercise training (HF-ACTION): design and rationale. Am Heart J. 2007 Feb;153(2):201-11.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Whellan DJ, Nigam A, Arnold M, Starr AZ, Hill J, Fletcher G, Ellis SJ, Cooper L, Onwuanyi A, Chandler B, Keteyian SJ, Ewald G, Kao A, Gheorghiade M. Benefit of exercise therapy for systolic heart failure in relation to disease severity and etiology-findings from the Heart Failure and A Controlled Trial Investigating Outcomes of Exercise Training study. Am Heart J. 2011 Dec;162(6):1003-10.

O'Connor CM, Whellan DJ, Wojdyla D, Leifer E, Clare RM, Ellis SJ, Fine LJ, Fleg JL, Zannad F, Keteyian SJ, Kitzman DW, Kraus WE, Rendall D, Piña IL, Cooper LS, Fiuzat M, Lee KL. Factors related to morbidity and mortality in patients with chronic heart failure with systolic dysfunction: the HF-ACTION predictive risk score model. Circ Heart Fail. 2012 Jan 1;5(1):63-71. Epub 2011 Nov 23.

Felker GM, Fiuzat M, Shaw LK, Clare R, Whellan DJ, Bettari L, Shirolkar SC, Donahue M, Kitzman DW, Zannad F, Piña IL, O'Connor CM. Galectin-3 in ambulatory patients with heart failure: results from the HF-ACTION study. Circ Heart Fail. 2012 Jan 1;5(1):72-8. Epub 2011 Oct 20.

Atchley AE, Iskandrian AE, Bensimhon D, Ellis SJ, Kitzman DW, Shaw LK, Pagnanelli RA, Whellan DJ, Gardin JM, Kao A, Abdul-Nour K, Ewald G, Walsh MN, Kraus WE, O'Connor CM, Borges-Neto S; HF-ACTION Trial Nuclear Ancillary Study Investigators. Relationship of technetium-99m tetrofosmin-gated rest single-photon emission computed tomography myocardial perfusion imaging to death and hospitalization in heart failure patients: results from the nuclear ancillary study of the HF-ACTION trial. Am Heart J. 2011 Jun;161(6):1038-45. Epub 2011 Apr 6.

Reed SD, Whellan DJ, Li Y, Friedman JY, Ellis SJ, Piña IL, Settles SJ, Davidson-Ray L, Johnson JL, Cooper LS, O'Connor CM, Schulman KA; HF-ACTION Investigators. Economic evaluation of the HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) randomized controlled trial: an exercise training study of patients with chronic heart failure. Circ Cardiovasc Qual Outcomes. 2010 Jul;3(4):374-81. Epub 2010 Jun 15.

Keteyian SJ, Isaac D, Thadani U, Roy BA, Bensimhon DR, McKelvie R, Russell SD, Hellkamp AS, Kraus WE; HF-ACTION Investigators. Safety of symptom-limited cardiopulmonary exercise testing in patients with chronic heart failure due to severe left ventricular systolic dysfunction. Am Heart J. 2009 Oct;158(4 Suppl):S72-7.

Flynn KE, Lin L, Ellis SJ, Russell SD, Spertus JA, Whellan DJ, Piña IL, Fine LJ, Schulman KA, Weinfurt KP; HF-ACTION Investigators. Outcomes, health policy, and managed care: relationships between patient-reported outcome measures and clinical measures in outpatients with heart failure. Am Heart J. 2009 Oct;158(4 Suppl):S64-71.

Atchley AE, Kitzman DW, Whellan DJ, Iskandrian AE, Ellis SJ, Pagnanelli RA, Kao A, Abdul-Nour K, O'Connor CM, Ewald G, Kraus WE, Borges-Neto S; HF-ACTION Investigators. Myocardial perfusion, function, and dyssynchrony in patients with heart failure: baseline results from the single-photon emission computed tomography imaging ancillary study of the Heart Failure and A Controlled Trial Investigating Outcomes of Exercise TraiNing (HF-ACTION) Trial. Am Heart J. 2009 Oct;158(4 Suppl):S53-63.

Felker GM, Whellan D, Kraus WE, Clare R, Zannad F, Donahue M, Adams K, McKelvie R, Piña IL, O'Connor CM; HF-ACTION Investigators. N-terminal pro-brain natriuretic peptide and exercise capacity in chronic heart failure: data from the Heart Failure and a Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION) study. Am Heart J. 2009 Oct;158(4 Suppl):S37-44.

Horwich TB, Leifer ES, Brawner CA, Fitz-Gerald MB, Fonarow GC; HF-ACTION Investigators. The relationship between body mass index and cardiopulmonary exercise testing in chronic systolic heart failure. Am Heart J. 2009 Oct;158(4 Suppl):S31-6.

Russell SD, Saval MA, Robbins JL, Ellestad MH, Gottlieb SS, Handberg EM, Zhou Y, Chandler B; HF-ACTION Investigators. New York Heart Association functional class predicts exercise parameters in the current era. Am Heart J. 2009 Oct;158(4 Suppl):S24-30.

Piña IL, Kokkinos P, Kao A, Bittner V, Saval M, Clare B, Goldberg L, Johnson M, Swank A, Ventura H, Moe G, Fitz-Gerald M, Ellis SJ, Vest M, Cooper L, Whellan D; HF-ACTION Investigators. Baseline differences in the HF-ACTION trial by sex. Am Heart J. 2009 Oct;158(4 Suppl):S16-23.

Flynn KE, Piña IL, Whellan DJ, Lin L, Blumenthal JA, Ellis SJ, Fine LJ, Howlett JG, Keteyian SJ, Kitzman DW, Kraus WE, Miller NH, Schulman KA, Spertus JA, O'Connor CM, Weinfurt KP. Effects of exercise training on health status in patients with chronic heart failure: HF-ACTION randomized controlled trial. JAMA. 2009 Apr 8;301(14):1451-9.

O'Connor CM, Whellan DJ, Lee KL, Keteyian SJ, Cooper LS, Ellis SJ, Leifer ES, Kraus WE, Kitzman DW, Blumenthal JA, Rendall DS, Miller NH, Fleg JL, Schulman KA, McKelvie RS, Zannad F, Piña IL; HF-ACTION Investigators. Efficacy and safety of exercise training in patients with chronic heart failure: HF-ACTION randomized controlled trial. JAMA. 2009 Apr 8;301(14):1439-50.

Responsible Party:	Christopher O'Connor, Duke Clinical Research Institute at Duke University Medical Center
ClinicalTrials.gov Identifier:	NCT00047437 History of Changes
Other Study ID Numbers:	149, U01 HL63747, U01 HL64250, U01 HL64257, U01 HL64264, U01 HL64265, U01 HL66461, U01 HL66482, U01 HL66491, U01 HL66494, U01 HL66497, U01 HL66501, U01 HL68973, U01 HL68980
Study First Received:	October 3, 2002
Last Updated:	February 20, 2009
Health Authority:	United States: Federal Government

Additional relevant MeSH terms:

Cardiovascular Diseases
Heart Diseases
Heart Failure

ClinicalTrials.gov processed this record on May 21, 2012