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Heart FailureNCT00271154

REsynchronization reVErses Remodeling in Systolic Left vEntricular Dysfunction (REVERSE)

A study testing Cardiac Resynchronization Therapy (CRT) Device or Implantable Cardioverter Defibrillator (ICD) with CRT in people with Heart Failure, run by Medtronic Cardiac Rhythm and Heart Failure at 65 sites in 15 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Heart Failure
What is being tested?
Cardiac Resynchronization Therapy (CRT) Device or Implantable Cardioverter Defibrillator (ICD) with CRT
Type of treatment
Medical device
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
684 participants
Where
65 sitesin 15 countries
Study dates
Sep 2004to Nov 2011
Phase
Interventional
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.)

Who cannot join

  • 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.

Trial locations and contacts

65 sites in 15 countries.

65 sites in 15 countries

United States34 sites
  • Study site

    Anchorage, Alaska

  • Study site

    Ann Arbor, Michigan

  • Study site

    Atlantis, Florida

  • Study site

    Austin, Texas

  • Study site

    Boston, Massachusetts

  • Study site

    Burlington, Massachusetts

  • Study site

    Charleston, South Carolina

  • Study site

    Cincinnati, Ohio

  • Study site

    Columbus, Ohio

  • Study site

    Coon Rapids, Minnesota

  • Study site

    Des Moines, Iowa

  • Study site

    Doylestown, Pennsylvania

  • Study site

    East Syracuse, New York

  • Study site

    Germantown, Tennessee

  • Study site

    Hershey, Pennsylvania

  • Study site

    Houston, Texas

  • Study site

    Huntsville, Alabama

  • Study site

    Indianapolis, Indiana

  • Study site

    Jacksonville, Florida

  • Study site

    Kingsport, Tennessee

  • Study site

    Lincoln, Nebraska

  • Study site

    Madison, Wisconsin

  • Study site

    Manhasset, New York

  • Study site

    Marion, Ohio

  • Study site

    Norfolk, Virginia

  • Study site

    Redwood City, California

  • Study site

    Richmond, Virginia

  • Study site

    Saginaw, Michigan

  • Study site

    Salt Lake City, Utah

  • Study site

    San Diego, California

  • Study site

    Springfield, Illinois

  • Study site

    Tupelo, Mississippi

  • Study site

    West Reading, Pennsylvania

  • Study site

    Winston-Salem, North Carolina

Other trials in United States

France5 sites
  • Study site

    Lyon

  • Study site

    Marseille

  • Study site

    Montpellier

  • Study site

    Nantes

  • Study site

    Rennes

Other trials in France

Denmark4 sites
  • Study site

    Aalborg

  • Study site

    Aarhus

  • Study site

    Copenhagen

  • Study site

    Odense

Other trials in Denmark

Italy4 sites
  • Study site

    Busto Arsizio

  • Study site

    Florence

  • Study site

    Milan

  • Study site

    Rome

Other trials in Italy

Germany3 sites
  • Study site

    Bochum

  • Study site

    Hamburg

  • Study site

    Hanover

Other trials in Germany

Austria2 sites
  • Study site

    Sankt Pölten

  • Study site

    Weiner Neustadt

Other trials in Austria

Czechia2 sites
  • Study site

    Brno

  • Study site

    Olomouc

Other trials in Czechia

Hungary2 sites
  • Study site

    Budapest

  • Study site

    Szeged

Other trials in Hungary

Spain2 sites
  • Study site

    Madrid

  • Study site

    Valencia

Other trials in Spain

Sweden2 sites
  • Study site

    Linköping

  • Study site

    Stockholm

Other trials in Sweden

Belgium1 site
  • Study site

    Leuven

Other trials in Belgium

Canada1 site
  • Study site

    Kingston, Ontario

Other trials in Canada

Ireland1 site
  • Study site

    Dublin

Other trials in Ireland

Norway1 site
  • Study site

    Kristiansand

Other trials in Norway

United Kingdom1 site
  • Study site

    Blackpool

Other trials in United Kingdom

About this study

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
Being tested
Cardiac Resynchronization Therapy (CRT) Device or Implantable Cardioverter Defibrillator (ICD) with CRT
Keywords
Heart Failure, Implantable Cardioverter Defibrillator, Cardiac Resynchronization Therapy
Medical subject headings
Heart Failure

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

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

Study groups in NCT00271154
Study groupRoleWhat they receive
CRT OFFPlacebo comparatorCardiac Resynchronization Therapy (CRT) turned OFF in conjunction with optimal medical therapy
Receives: Device: Cardiac Resynchronization Therapy (CRT) Device or Implantable Cardioverter Defibrillator (ICD) with CRT
CRT ONActive comparatorCardiac Resynchronization Therapy (CRT) turned ON in conjunction with optimal medical therapy
Receives: Device: Cardiac Resynchronization Therapy (CRT) Device or Implantable Cardioverter Defibrillator (ICD) with CRT

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 12 Months

Secondary outcomes (1)
  1. Change in Left Ventricular End Systolic Volume, Indexed (LVESVi)

    The change is LVESVi measured at 12 months minus LVESVi measured at baseline. The 12-month echocardiographic measurements were made with CRT programmed off, irespective of the treatment assignment. In CRT ON patients these measurements were recorded after a 10 minute washout period. Two core laboratories performed all echo measurements.

    Measured: Baseline to 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Dec 2005 (estimated)
  2. Study startSep 2004
  3. Primary completionOct 2007
  4. Study completionNov 2011

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
684 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00271154
Sponsor's protocol ID
233
Status last verified
Jan 2012
First submitted
21 Dec 2005
Last updated
30 Jan 2012
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 19038680
  • 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.

    PubMed 18401214
  • 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.

    PubMed 40324513
  • 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.

    PubMed 37671601
  • 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.

    PubMed 36700426
  • 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.

    PubMed 36442825
  • 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.

    PubMed 33640347
  • 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.

    PubMed 29759777
  • 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.

    PubMed 29314424
  • 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.

    PubMed 28254126
  • 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.

    PubMed 28254122
  • 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.

    PubMed 26363005
  • 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.

    PubMed 24125796
  • 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.

    PubMed 24014828
  • 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.

    PubMed 23900696

Questions about this trial

What is this clinical trial studying?

A study testing Cardiac Resynchronization Therapy (CRT) Device or Implantable Cardioverter Defibrillator (ICD) with CRT in people with Heart Failure, run by Medtronic Cardiac Rhythm and Heart Failure at 65 sites in 15 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 30 Jan 2012. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 65 sites in United States, France, Denmark, Italy, Germany and 10 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 13 May 2009). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Patients Worsened for Clinical Composite Response (time frame: 12 Months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00271154, which also lists 23 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jan 2012.

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Clinical Trial NCT00271154 | AzTrials