Clinical trial NCT00271154: REsynchronization reVErses Remodeling in Systolic Left vEntricular Dysfunction (REVERSE)
Official title: REsynchronization reVErses Remodeling in Systolic Left vEntricular Dysfunction (REVERSE)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Heart Failure
Keywords: Heart Failure
Implantable Cardioverter Defibrillator
Cardiac Resynchronization Therapy
Lead sponsor: Medtronic Cardiac Rhythm and Heart Failure
Sponsor class: INDUSTRY
First posted: 2005-12-30
Enrollment: 684
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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.)

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Percentage of Patients Worsened for Clinical Composite Response
timeFrame: 12 Months
Secondary outcomes:
measure: Change in Left Ventricular End Systolic Volume, Indexed (LVESVi)
timeFrame: Baseline to 12 months
Other outcomes:
Locations:
city: Huntsville
country: United States
state: Alabama
city: Anchorage
country: United States
state: Alaska
city: Redwood City
country: United States
state: California
city: San Diego
country: United States
state: California
city: Atlantis
country: United States
state: Florida
city: Jacksonville
country: United States
state: Florida
city: Springfield
country: United States
state: Illinois
city: Indianapolis
country: United States
state: Indiana
city: Des Moines
country: United States
state: Iowa
city: Boston
country: United States
state: Massachusetts
city: Burlington
country: United States
state: Massachusetts
city: Ann Arbor
country: United States
state: Michigan
city: Saginaw
country: United States
state: Michigan
city: Coon Rapids
country: United States
state: Minnesota
city: Tupelo
country: United States
state: Mississippi
city: Lincoln
country: United States
state: Nebraska
city: East Syracuse
country: United States
state: New York
city: Manhasset
country: United States
state: New York
city: Winston-Salem
country: United States
state: North Carolina
city: Cincinnati
country: United States
state: Ohio
city: Columbus
country: United States
state: Ohio
city: Marion
country: United States
state: Ohio
city: Doylestown
country: United States
state: Pennsylvania
city: Hershey
country: United States
state: Pennsylvania
city: West Reading
country: United States
state: Pennsylvania
city: Charleston
country: United States
state: South Carolina
city: Germantown
country: United States
state: Tennessee
city: Kingsport
country: United States
state: Tennessee
city: Austin
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Salt Lake City
country: United States
state: Utah
city: Norfolk
country: United States
state: Virginia
city: Richmond
country: United States
state: Virginia
city: Madison
country: United States
state: Wisconsin
city: St. Polten
country: Austria
city: Weiner Neustadt
country: Austria
city: Leuven
country: Belgium
city: Kingston
country: Canada
state: Ontario
city: Brno
country: Czech Republic
city: Olomouc
country: Czech Republic
city: Aalborg
country: Denmark
city: Aarhus
country: Denmark
city: Copenhagen
country: Denmark
city: Odense
country: Denmark
city: Lyon
country: France
city: Marseille
country: France
city: Montpellier
country: France
city: Nantes
country: France
city: Rennes
country: France
city: Bochum
country: Germany
city: Hamburg
country: Germany
city: Hannover
country: Germany
city: Budapest
country: Hungary
city: Szeged
country: Hungary
city: Dublin
country: Ireland
city: Busto Arsizio
country: Italy
city: Florence
country: Italy
city: Milano
country: Italy
city: Rome
country: Italy
city: Kristiansand
country: Norway
city: Madrid
country: Spain
city: Valencia
country: Spain
city: Linkoping
country: Sweden
city: Stockholm
country: Sweden
city: Blackpool
country: United Kingdom
Study officials:
affiliation: Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden
name: Cecilia Linde, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.