REsynchronization reVErses Remodeling in Systolic Left vEntricular Dysfunction (REVERSE)

NCT00271154 | Completed Results DMC

• 1 other identifier: 233
• Study Type: interventional
• Target: 684
• Locations: 15 countries
• Sites: 65

Brief Summary

Heart failure is a progressive disease that decreases the pumping action of the heart. This may cause a backup of fluid in the heart and may result in heart beat changes. When there are changes in the heart beat sometimes an implantable heart device is used to control the rate and rhythm of the heart beat. The purpose of the REVERSE clinical trial is to determine whether pacing in both the left and right ventricles using Cardiac Resynchronization Therapy (CRT) can help slow the progression of heart failure in people who have mild or previous symptoms and poor heart pumping function. This kind of therapy has previously been shown to reduce symptoms and improve exercise capacity in people with more advanced forms of heart failure.

Conditions

Heart Failure

Keywords

Heart Failure; Implantable Cardioverter Defibrillator; Cardiac Resynchronization Therapy

Outcome Measures

Primary Outcomes (1)

• Percentage of Patients Worsened for Clinical Composite Response

  Patients considered worsened if they died, were hospitalized with worsening heart failure (HF), crossed over to other arm, demonstrated worsening in New York Heart Association (NYHA) functional class, or reported moderately/markedly worse HF symptoms compared to before CRT implant.

  12 Months

Secondary Outcomes (1)

• Change in Left Ventricular End Systolic Volume, Indexed (LVESVi)

  Baseline to 12 months

Study Arms (2)

CRT OFF

PLACEBO COMPARATOR

Cardiac Resynchronization Therapy (CRT) turned OFF in conjunction with optimal medical therapy

Device: Cardiac Resynchronization Therapy (CRT) Device or Implantable Cardioverter Defibrillator (ICD) with CRT

CRT ON

ACTIVE COMPARATOR

Cardiac Resynchronization Therapy (CRT) turned ON in conjunction with optimal medical therapy

Device: Cardiac Resynchronization Therapy (CRT) Device or Implantable Cardioverter Defibrillator (ICD) with CRT

Interventions

Cardiac Resynchronization Therapy (CRT) Device or Implantable Cardioverter Defibrillator (ICD) with CRT DEVICE

All randomized patients will be implanted with a market-released Medtronic CRT or CRT/ICD device.

CRT OFF; CRT ON

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects with previously symptomatic heart failure but no current symptoms (New York Heart Association (NYHA) Class I, Stage C) or subjects with mild heart failure that only sometimes interferes with daily activities (NYHA Class II)
• Subjects with a QRS of 120 ms or more (The QRS interval is a measurement of how the electrical signal involved in a heart beat travels/conducts through the ventricles. A wide QRS (120 ms or more) suggests that there is a conduction problem (or block) in the ventricles).
• Subjects with a left ventricular ejection fraction less than or equal to 40%. (The left ventricular ejection fraction (LVEF) is a measurement of how well the left ventricle pumps blood out to the rest of the body. The higher the LVEF the more blood the ventricle is pumping.)
• Subjects with a left ventricular end diastolic dimension (LVEDD) greater than or equal to 55. (The left ventricular end diastolic dimension (LVEDD) is a measurement of heart size taken during an echocardiogram that is one indication of the health of the left ventricle.)

You may not qualify if:

• Subjects who are pacemaker dependent (heart would not beat without the help of an implanted device to pace it).
• Subjects with heart failure that severely limits daily activities (NYHA Class III) or subjects with severe heart failure with symptoms while resting (NYHA Class IV).
• Subjects hospitalized due to heart failure within past 3 months.

Sponsors & Collaborators

• Medtronic Cardiac Rhythm and Heart Failure: lead

Study Sites (65)

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Huntsville, Alabama, United States

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Anchorage, Alaska, United States

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Redwood City, California, United States

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San Diego, California, United States

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Atlantis, Florida, United States

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Jacksonville, Florida, United States

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Springfield, Illinois, United States

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Indianapolis, Indiana, United States

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Des Moines, Iowa, United States

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Boston, Massachusetts, United States

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Burlington, Massachusetts, United States

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Ann Arbor, Michigan, United States

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Saginaw, Michigan, United States

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Coon Rapids, Minnesota, United States

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Tupelo, Mississippi, United States

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Lincoln, Nebraska, United States

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East Syracuse, New York, United States

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Manhasset, New York, United States

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Winston-Salem, North Carolina, United States

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Cincinnati, Ohio, United States

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Columbus, Ohio, United States

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Marion, Ohio, United States

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Doylestown, Pennsylvania, United States

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Hershey, Pennsylvania, United States

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West Reading, Pennsylvania, United States

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Charleston, South Carolina, United States

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Germantown, Tennessee, United States

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Kingsport, Tennessee, United States

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Austin, Texas, United States

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Houston, Texas, United States

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Salt Lake City, Utah, United States

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Norfolk, Virginia, United States

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Richmond, Virginia, United States

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Madison, Wisconsin, United States

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Sankt Pölten, Austria

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Weiner Neustadt, Austria

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Leuven, Belgium

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Kingston, Ontario, Canada

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Brno, Czechia

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Olomouc, Czechia

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Aalborg, Denmark

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Aarhus, Denmark

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Copenhagen, Denmark

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Odense, Denmark

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Lyon, France

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Marseille, France

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Montpellier, France

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Nantes, France

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Rennes, France

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Bochum, Germany

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Hamburg, Germany

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Hanover, Germany

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Budapest, Hungary

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Szeged, Hungary

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Dublin, Ireland

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Busto Arsizio, Italy

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Florence, Italy

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Milan, Italy

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Rome, Italy

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Kristiansand, Norway

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Madrid, Spain

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Valencia, Spain

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Linköping, Sweden

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Stockholm, Sweden

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Blackpool, United Kingdom

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Related Publications (23)

• Linde C, Abraham WT, Gold MR, St John Sutton M, Ghio S, Daubert C; REVERSE (REsynchronization reVErses Remodeling in Systolic left vEntricular dysfunction) Study Group. Randomized trial of cardiac resynchronization in mildly symptomatic heart failure patients and in asymptomatic patients with left ventricular dysfunction and previous heart failure symptoms. J Am Coll Cardiol. 2008 Dec 2;52(23):1834-1843. doi: 10.1016/j.jacc.2008.08.027. Epub 2008 Nov 7.

  PMID: 19038680 RESULT

• Linde C, Gold M, Abraham WT, Daubert JC; REVERSE Study Group. Baseline characteristics of patients randomized in The Resynchronization Reverses Remodeling In Systolic Left Ventricular Dysfunction (REVERSE) study. Congest Heart Fail. 2008 Mar-Apr;14(2):66-74. doi: 10.1111/j.1751-7133.2008.07613.x.

  PMID: 18401214 RESULT

• Gold MR, Abraham WT, Butler J, Zile MR, Kahwash R, Gerritse B, Linde C. Win ratio analysis of the REVERSE cardiac resynchronization trial. Heart Rhythm. 2025 Dec;22(12):3042-3049. doi: 10.1016/j.hrthm.2025.04.059. Epub 2025 May 3.

  PMID: 40324513 DERIVED

• Fudim M, Dalgaard F, Friedman DJ, Abraham WT, Cleland JGF, Curtis AB, Gold MR, Kutyifa V, Linde C, Ali-Ahmed F, Tang A, Olivas-Martinez A, Inoue LYT, Al-Khatib SM, Sanders GD. Comorbidities and clinical response to cardiac resynchronization therapy: Patient-level meta-analysis from eight clinical trials. Eur J Heart Fail. 2024 Apr;26(4):1039-1046. doi: 10.1002/ejhf.3029. Epub 2023 Sep 15.

  PMID: 37671601 DERIVED

• Friedman DJ, Al-Khatib SM, Dalgaard F, Fudim M, Abraham WT, Cleland JGF, Curtis AB, Gold MR, Kutyifa V, Linde C, Tang AS, Ali-Ahmed F, Olivas-Martinez A, Inoue LYT, Sanders GD. Cardiac Resynchronization Therapy Improves Outcomes in Patients With Intraventricular Conduction Delay But Not Right Bundle Branch Block: A Patient-Level Meta-Analysis of Randomized Controlled Trials. Circulation. 2023 Mar 7;147(10):812-823. doi: 10.1161/CIRCULATIONAHA.122.062124. Epub 2023 Jan 26.

  PMID: 36700426 DERIVED

• Gold MR, Rickard J, Daubert JC, Cerkvenik J, Linde C. Association of left ventricular remodeling with cardiac resynchronization therapy outcomes. Heart Rhythm. 2023 Feb;20(2):173-180. doi: 10.1016/j.hrthm.2022.11.016. Epub 2022 Nov 25.

  PMID: 36442825 DERIVED

• Gold MR, Rickard J, Daubert JC, Zimmerman P, Linde C. Redefining the Classifications of Response to Cardiac Resynchronization Therapy: Results From the REVERSE Study. JACC Clin Electrophysiol. 2021 Jul;7(7):871-880. doi: 10.1016/j.jacep.2020.11.010. Epub 2021 Feb 24.

  PMID: 33640347 DERIVED

• Senfield J, Daubert C, Abraham WT, Ghio S, St John Sutton M, Cerkvenik J, Linde C, Gold MR. The Impact of the PR Interval in Patients Receiving Cardiac Resynchronization Therapy: Results From the REVERSE Study. JACC Clin Electrophysiol. 2017 Aug;3(8):818-826. doi: 10.1016/j.jacep.2017.01.017. Epub 2017 Apr 26.

  PMID: 29759777 DERIVED

• Linde C, Cleland JGF, Gold MR, Claude Daubert J, Tang ASL, Young JB, Sherfesee L, Abraham WT. The interaction of sex, height, and QRS duration on the effects of cardiac resynchronization therapy on morbidity and mortality: an individual-patient data meta-analysis. Eur J Heart Fail. 2018 Apr;20(4):780-791. doi: 10.1002/ejhf.1133. Epub 2018 Jan 4.

  PMID: 29314424 DERIVED

• Gold MR, Padhiar A, Mealing S, Sidhu MK, Tsintzos SI, Abraham WT. Economic Value and Cost-Effectiveness of Cardiac Resynchronization Therapy Among Patients With Mild Heart Failure: Projections From the REVERSE Long-Term Follow-Up. JACC Heart Fail. 2017 Mar;5(3):204-212. doi: 10.1016/j.jchf.2016.10.014. Epub 2017 Jan 11.

  PMID: 28254126 DERIVED

• St John Sutton M, Linde C, Gold MR, Abraham WT, Ghio S, Cerkvenik J, Daubert JC; REVERSE Study Group. Left Ventricular Architecture, Long-Term Reverse Remodeling, and Clinical Outcome in Mild Heart Failure With Cardiac Resynchronization: Results From the REVERSE Trial. JACC Heart Fail. 2017 Mar;5(3):169-178. doi: 10.1016/j.jchf.2016.11.012.

  PMID: 28254122 DERIVED

• St John Sutton M, Cerkvenik J, Borlaug BA, Daubert C, Gold MR, Ghio S, Chirinos JA, Linde C, Ky B. Effects of Cardiac Resynchronization Therapy on Cardiac Remodeling and Contractile Function: Results From Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction (REVERSE). J Am Heart Assoc. 2015 Sep 11;4(9):e002054. doi: 10.1161/JAHA.115.002054.

  PMID: 26363005 DERIVED

• Gold MR, Daubert JC, Abraham WT, Hassager C, Dinerman JL, Hudnall JH, Cerkvenik J, Linde C. Implantable defibrillators improve survival in patients with mildly symptomatic heart failure receiving cardiac resynchronization therapy: analysis of the long-term follow-up of remodeling in systolic left ventricular dysfunction (REVERSE). Circ Arrhythm Electrophysiol. 2013 Dec;6(6):1163-8. doi: 10.1161/CIRCEP.113.000570. Epub 2013 Oct 14.

  PMID: 24125796 DERIVED

• Linde C, Daubert C, Abraham WT, St John Sutton M, Ghio S, Hassager C, Herre JM, Bergemann TL, Gold MR; REsynchronization reVErses Remodeling in Systolic left vEntricular dysfunction (REVERSE) Study Group. Impact of ejection fraction on the clinical response to cardiac resynchronization therapy in mild heart failure. Circ Heart Fail. 2013 Nov;6(6):1180-9. doi: 10.1161/CIRCHEARTFAILURE.113.000326. Epub 2013 Sep 6.

  PMID: 24014828 DERIVED

• Cleland JG, Abraham WT, Linde C, Gold MR, Young JB, Claude Daubert J, Sherfesee L, Wells GA, Tang AS. An individual patient meta-analysis of five randomized trials assessing the effects of cardiac resynchronization therapy on morbidity and mortality in patients with symptomatic heart failure. Eur Heart J. 2013 Dec;34(46):3547-56. doi: 10.1093/eurheartj/eht290. Epub 2013 Jul 29.

  PMID: 23900696 DERIVED

• Linde C, Gold MR, Abraham WT, St John Sutton M, Ghio S, Cerkvenik J, Daubert C; REsynchronization reVErses Remodeling in Systolic left vEntricular dysfunction Study Group. Long-term impact of cardiac resynchronization therapy in mild heart failure: 5-year results from the REsynchronization reVErses Remodeling in Systolic left vEntricular dysfunction (REVERSE) study. Eur Heart J. 2013 Sep;34(33):2592-9. doi: 10.1093/eurheartj/eht160. Epub 2013 May 2.

  PMID: 23641006 DERIVED

• Gold MR, Thebault C, Linde C, Abraham WT, Gerritse B, Ghio S, St John Sutton M, Daubert JC. Effect of QRS duration and morphology on cardiac resynchronization therapy outcomes in mild heart failure: results from the Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction (REVERSE) study. Circulation. 2012 Aug 14;126(7):822-9. doi: 10.1161/CIRCULATIONAHA.112.097709. Epub 2012 Jul 10.

  PMID: 22781424 DERIVED

• Thebault C, Donal E, Meunier C, Gervais R, Gerritse B, Gold MR, Abraham WT, Linde C, Daubert JC; REVERSE study group. Sites of left and right ventricular lead implantation and response to cardiac resynchronization therapy observations from the REVERSE trial. Eur Heart J. 2012 Nov;33(21):2662-71. doi: 10.1093/eurheartj/ehr505. Epub 2012 Jan 26.

  PMID: 22285578 DERIVED

• Gold MR, Linde C, Abraham WT, Gardiwal A, Daubert JC. The impact of cardiac resynchronization therapy on the incidence of ventricular arrhythmias in mild heart failure. Heart Rhythm. 2011 May;8(5):679-84. doi: 10.1016/j.hrthm.2010.12.031. Epub 2010 Dec 23.

  PMID: 21185401 DERIVED

• Linde C, Abraham WT, Gold MR, Daubert C; REVERSE Study Group. Cardiac resynchronization therapy in asymptomatic or mildly symptomatic heart failure patients in relation to etiology: results from the REVERSE (REsynchronization reVErses Remodeling in Systolic Left vEntricular Dysfunction) study. J Am Coll Cardiol. 2010 Nov 23;56(22):1826-31. doi: 10.1016/j.jacc.2010.05.055.

  PMID: 21087711 DERIVED

• Linde C, Daubert C. Cardiac resynchronization therapy in patients with New York Heart Association class I and II heart failure: an approach to 2010. Circulation. 2010 Sep 7;122(10):1037-43. doi: 10.1161/CIRCULATIONAHA.109.923094. No abstract available.

  PMID: 20823398 DERIVED

• St John Sutton M, Ghio S, Plappert T, Tavazzi L, Scelsi L, Daubert C, Abraham WT, Gold MR, Hassager C, Herre JM, Linde C; REsynchronization reVErses Remodeling in Systolic left vEntricular dysfunction (REVERSE) Study Group. Cardiac resynchronization induces major structural and functional reverse remodeling in patients with New York Heart Association class I/II heart failure. Circulation. 2009 Nov 10;120(19):1858-65. doi: 10.1161/CIRCULATIONAHA.108.818724. Epub 2009 Oct 26.

  PMID: 19858419 DERIVED

• Daubert C, Gold MR, Abraham WT, Ghio S, Hassager C, Goode G, Szili-Torok T, Linde C; REVERSE Study Group. Prevention of disease progression by cardiac resynchronization therapy in patients with asymptomatic or mildly symptomatic left ventricular dysfunction: insights from the European cohort of the REVERSE (Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction) trial. J Am Coll Cardiol. 2009 Nov 10;54(20):1837-46. doi: 10.1016/j.jacc.2009.08.011. Epub 2009 Oct 1.

  PMID: 19800193 DERIVED

MeSH Terms

Conditions

Heart Failure

Interventions

Cardiac Resynchronization Therapy; Defibrillators, Implantable

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Cardiac Pacing, Artificial; Electric Stimulation Therapy; Therapeutics; Defibrillators; Electrodes; Electrical Equipment and Supplies; Equipment and Supplies; Electrodes, Implanted; Prostheses and Implants

Results Point of Contact

• Title: CRDM Core Clinical
• Organization: Medtronic CRDM

medtroniccrmtrials@medtronic.com

800-328-2518

Study Officials

• Cecilia Linde, MD, PhD

  Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 21, 2005
• First Posted: December 30, 2005
• Study Start: September 1, 2004
• Primary Completion: October 1, 2007
• Study Completion: November 1, 2011
• Last Updated: January 30, 2012
• Results First Posted: May 13, 2009

Record last verified: 2012-01

Locations

GB (1); FR (5); SE (2); BE (1); AU (2); HU (2); ES (2); US (34); NO (1); IE (1); DK (4); DE (3); IT (4); CA (1); CZ (2)