Remission From Stage D Heart Failure (RESTAGE-HF)

Study Description

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Brief Summary:

The purpose of this study is to determine the proportion of subjects who have sufficient improvement in ventricular function after undergoing a standardized Left Ventricular Assist Device (LVAD) plus pharmacologic recovery treatment and testing protocol to allow removal of the LVAD within 18 months.

Condition or disease	Intervention/treatment	Phase
Heart Failure NYHA Class III; Heart Failure NYHA Class IV	Drug: Pharmacological Treatment	Phase 4

Detailed Description:

The encouraging results from the LVAD based recovery series suggest that the significant hemodynamic unloading provided by the Mechanical Circulatory Support (MCS) in conjunction with aggressive pharmacological treatment may induce a profound reverse structural remodeling and in turn result in a curative alternative to a specific patient population with severe heart failure. The active identification and characterization of the patients with a high potential for full cardiac function recovery is of paramount importance. The development of a standard and simplified recovery protocol would ultimately lead to a larger bridge to recovery patient population. The primary objective of this study is to determine the proportion of subjects who have sufficient improvement in ventricular function (remission from heart failure) after undergoing a standardized LVAD plus pharmacologic recovery treatment and testing protocol to allow removal of the LVAD within 18 months. The secondary objectives of this study are twofold, first to determine the durability of sustained remission from HF following LVAD explantation at 12 months and up to 3 years and second to determine the predictors of recovery.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	40 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Remission From Stage D Heart Failure (RESTAGE-HF)
Study Start Date :	January 2013
Estimated Primary Completion Date :	December 2017
Estimated Study Completion Date :	December 2017

Arms and Interventions

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Arm

Intervention/treatment

Experimental: HeartMate II plus Pharmacological Treat; The HM II pump contains a single moving component, the rotor. The pump is implanted just below the left hemidiaphragm with the inflow attached to the apex of the left ventricle and the outflow graft anastomosed to the ascending aorta. Blood is pumped continuously throughout the cardiac cycle from the left ventricle to the aorta. The pharmacological treatment intended to enhance reverse remodeling includes 4 drugs initiated immediately after weaning of inotropic support once achieving adequate end-organ recovery and titrated (against symptoms, potassium, and renal function) to the following maximum doses: lisinopril 40 mg daily; carvedilol 25 mg 3 times daily; spironolactone 25 mg daily; digoxin 125g daily, and losartan 150 mg daily.

Drug: Pharmacological Treatment; The pharmacological treatment intended to enhance reverse remodeling includes 4 drugs initiated immediately after weaning of inotropic support once achieving adequate end-organ recovery and titrated (against symptoms, potassium, and renal function) to the following maximum doses: lisinopril 40 mg daily; carvedilol 25 mg 3 times daily; spironolactone 25 mg daily; digoxin 125g daily, and losartan 150 mg daily.

Outcome Measures

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Primary Outcome Measures :

1. Proportion of subjects who experience LVAD removal and subsequent freedom from mechanical circulatory support or heart transplantation [ Time Frame: 12 months ]

Secondary Outcome Measures :

1. The proportion of evaluable subjects meeting explant criteria and subsequently explanted [ Time Frame: 6 weeks, 3, 4, 5, 6, 9, 12-18 months ]
2. The time course of reverse remodeling on a left ventricular assist device [ Time Frame: 6 weeks, 3, 4, 5, 6, 9, 12-18 months ]
3. The time course and sustainability of reverse remodeling following LVAD explantation [ Time Frame: 12-18 months ]
4. Predictors of recovery and device removal [ Time Frame: 6 weeks, 3, 4, 5, 6, 9, 12-18 months ]
5. Changes in maximal and sub maximal exercise capacity [ Time Frame: 12-18 months ]
6. Changes in renal function and hepatic enzymes [ Time Frame: 6 weeks, 3, 4, 5, 6, 9, 12-18 months ]
7. Changes in EF measured at 6000RPM. [ Time Frame: 6 weeks, 4, 6, 9, 12-18 months ]
8. Changes in quality of life, as measured by the EuroQoL (EQ5D) [ Time Frame: 6 months ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 59 Years (Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

1. Subject age between 18 - 59 years, inclusive
2. Subject indicated for DT or BTT
3. Subject with severe clinical heart failure resistant to intensive medical therapy and requiring LVAD implantation
4. Subject with LVEF < 25% and cardiomegaly at the time of LVAD implantation as documented by radionuclide or contrast ventriculography or by echocardiography
5. Subject with non-ischemic etiology (confirmed by angiography either within 2 years of implantation or prior to explantation)
6. Subject have undergone HM II implantation within prior 4 weeks or planned for a HM II implant
7. Subject has a history of HF < 5 years.

Exclusion Criteria:

1. Subject has evidence of active acute myocarditis confirmed by histology
2. Subject has a history of previous CVA resulting in significant fixed motor deficit limiting ability to perform exercise testing
3. Subject has been implanted with a mechanical aortic and/or mitral valve(s)
4. Subject had an aortic valve closure
5. Subject diagnosed with a hypertrophic obstructive cardiomyopathy or sarcoidosis
6. Subject with LVEDD below normal confirmed by surface echocardiogram (restrictive cardiomyopathy)
7. Subject has irreversible multi-organ failure
8. Pregnant or lactating women or unwilling to utilize two reliable methods of birth control for women of childbearing age
9. Subject is diagnosed with a psychiatric disease, irreversible cognitive dysfunction or poor psychosocial issues that is likely to impair compliance with the study protocol
10. Subject with any condition, other than heart failure, that could limit survival to less than 2 years
11. Subject has a history of cardiac or other organ transplant
12. Subject is contraindicated to anticoagulation antiplatelet therapy
13. Subject requires acute or chronic renal replacement therapy (e.g. chronic dialysis) within 3 months prior to enrollment
14. Subject participating in any other clinical investigations involving another Mechanical Circulatory Support (MCS) device or heart failure related drug, or investigations which are likely to confound study results or affect study outcome.

Contacts and Locations

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Contacts

Contact: Chris Cunningham, PhD		chris.cunningham@louisville.edu

Locations

United States, Kentucky
University of Louisville	Recruiting
Louisville, Kentucky, United States, 40202
Contact: Terry Blanton, BSN, RN mtblan02@louisville.edu
Principal Investigator: Emma Birks, MD, PhD
United States, Nebraska
University of Nebraska Medical Center	Recruiting
Omaha, Nebraska, United States, 68198
Contact: Stacy Flickbohm, RN 402-559-5127 stacy.fickbohm@unmc.edu
Contact: Natalie Kamtz 402-559-3293 natalie.kamtz@unmc.edu
Principal Investigator: Brian D Lowes, MD, PhD
United States, New York
Montefiore Medical Center	Recruiting
New York, New York, United States, 10467
Contact: Auris Brown aubrowne@montefiore.org
Contact: Johanna Oviedo 718-920-8780 joviedo@montefiore.org
Principal Investigator: Snehal Patel, MD
United States, Ohio
Cleveland Clinic	Recruiting
Cleveland, Ohio, United States, 44195
Contact: Barb Gus, RN BSN CCRC 216-445-6552 GUSB@ccf.org
Principal Investigator: Maria Mountis, D.O.
United States, Pennsylvania
University of Pennsylvania	Recruiting
Philadelphia, Pennsylvania, United States, 19140
Contact: Judith Marble Judith.Marble@uphs.upenn.edu
Principal Investigator: J E Rame, MD
United States, Utah
University of Utah	Recruiting
Salt Lake City, Utah, United States, 84112
Contact: Ashley Elmer ashley.elmer@hsc.utah.edu
Principal Investigator: Craig Selzman, MD

Sponsors and Collaborators

University of Louisville

Thoratec Corporation

Investigators

Principal Investigator:	Emma Birks, MD	University of Louisville

More Information

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Responsible Party:	Emma Birks, M.D., Ph.D., University of Louisville
ClinicalTrials.gov Identifier:	NCT01774656 History of Changes
Other Study ID Numbers:	RESTAGE-UL
First Posted:	January 24, 2013
Last Update Posted:	April 27, 2017
Last Verified:	April 2017

Keywords provided by Emma Birks, University of Louisville:

heart-assist device

Additional relevant MeSH terms:

Heart Failure; Heart Diseases; Cardiovascular Diseases