REsynchronization reVErses Remodeling in Systolic Left vEntricular Dysfunction (REVERSE) - Study Results

Study Type:	Interventional
Study Design:	Randomized, Double Blind (Subject, Investigator), Active Control, Parallel Assignment
Condition:	Heart Failure
Intervention:	Device: Cardiac Resynchronization Therapy (CRT) Device or Implantable Cardioverter Defibrillator (ICD) with CRT

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Patients were enrolled from September 2004 through September 2006 at 73 sites located in the United States, Canada, and Europe.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
A total of 684 patients were enrolled in the study. Of these, 642 patients were attempted for cardiac resynchronization therapy (CRT) device implant. 21 were unsuccessful, leaving 621 patients successfully implanted with a CRT device. Of these 621 patients, 610 were randomized.

Reporting Groups

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

Participant Flow: Overall Study

	CRT OFF	CRT ON
STARTED	191	419
COMPLETED	191	419
NOT COMPLETED	0	0

Baseline Characteristics

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Reporting Groups

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

Baseline Measures

	CRT OFF	CRT ON	Total
Number of Participants [units: participants]	191	419	610
Age [units: participants]
<=18 years	0	0	0
Between 18 and 65 years	108	229	337
>=65 years	83	190	273
Age [units: years] Mean ± Standard Deviation	61.8 ± 11.6	62.9 ± 10.6	62.5 ± 11.0
Gender [units: participants]
Female	39	92	131
Male	152	327	479
Region of Enrollment [units: participants]
United States	108	235	343
Spain	9	18	27
Ireland	1	4	5
Austria	2	4	6
United Kingdom	6	9	15
Italy	5	12	17
France	15	34	49
Czech Republic	0	1	1
Hungary	6	13	19
Canada	1	4	5
Belgium	1	3	4
Denmark	19	46	65
Germany	6	11	17
Norway	3	4	7
Sweden	7	17	24
Netherlands	2	4	6

Outcome Measures

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1. Primary:

Percentage of Patients Worsened for Clinical Composite Response [ 12 Months ]

Measure Type	Primary
Measure Title	Percentage of Patients Worsened for Clinical Composite Response
Measure Description	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.
Time Frame	12 Months
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All randomized patients were included using Intent to Treat (ITT).

Reporting Groups

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

Measured Values

	CRT OFF	CRT ON
Number of Participants Analyzed [units: participants]	191	419
Percentage of Patients Worsened for Clinical Composite Response [units: Percentage of participants worsened]	21.5	16.0

Statistical Analysis 1 for Percentage of Patients Worsened for Clinical Composite Response

Groups ^[1]	All groups
Method ^[2]	Chi-squared
P Value ^[3]	0.10

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Null hypothesis: Percentage worsened in CRT OFF group = Percentage worsened in CRT ON group
[2]	Other relevant information, such as adjustments or degrees of freedom:
	Not Applicable
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Not Applicable

2. Secondary:

Change in Left Ventricular End Systolic Volume, Indexed (LVESVi) [ Baseline to 12 months ]

Measure Type	Secondary
Measure Title	Change in Left Ventricular End Systolic Volume, Indexed (LVESVi)
Measure Description	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.
Time Frame	Baseline to 12 months
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups

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

Measured Values

	CRT OFF	CRT ON
Number of Participants Analyzed [units: participants]	191	419
Change in Left Ventricular End Systolic Volume, Indexed (LVESVi) [units: milliliters per meters squared] Mean ± Standard Deviation	-1.3 ± 23.4	-18.4 ± 29.5

Statistical Analysis 1 for Change in Left Ventricular End Systolic Volume, Indexed (LVESVi)

Groups ^[1]	All groups
Method ^[2]	t-test, 2 sided
P Value ^[3]	<0.0001

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Null hypothesis: mean 12-month change in LVESVi in group 1 = mean 12-month change in LVESVi in group 2.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	Not Applicable
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Not Applicable

Serious Adverse Events

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Other Adverse Events

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More Information

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Certain Agreements:

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: In most cases, contracts allow investigators to publish study results per the publication plan/protocol following Medtronic's review to determine whether confidential information ("CI") is disclosed. Any such CI is deleted prior to publication/presentation. Medtronic may not censor/interfere with the publication except as described. Investigators may not publish any single-site publications until the main multi-site study publication has occurred.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact:

Name/Title: CRDM Core Clinical
Organization: Medtronic CRDM
phone: 800-328-2518
e-mail: medtroniccrmtrials@medtronic.com

Publications of Results:

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):1834-43. Epub 2008 Nov 7.

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.

Publications automatically indexed to this study:

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. Epub 2009 Oct 26.

Daubert C, Gold MR, Abraham WT, Ghio S, Hassager C, Goode G, Szili-Török 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. Epub 2009 Oct 1.

Responsible Party:	Medtronic CRDM ( CRDM Core Clinical )
Study ID Numbers:	233
Study First Received:	December 21, 2005
Results First Received:	December 24, 2008
Last Updated:	March 26, 2009
ClinicalTrials.gov Identifier:	NCT00271154 History of Changes
Health Authority:	United States: Food and Drug Administration