Clinical trial NCT01774656: Remission From Stage D Heart Failure
Official title: Remission From Stage D Heart Failure (RESTAGE-HF)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Heart Failure NYHA Class III
Heart Failure NYHA Class IV
Keywords: heart-assist device
Lead sponsor: University of Louisville
Sponsor class: OTHER
Collaborators: name: Thoratec Corporation
First posted: 2013-01-24
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 59
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility 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.

Primary outcomes:
measure: Proportion of subjects who experience LVAD removal and subsequent freedom from mechanical circulatory support or heart transplantation
timeFrame: 12 months
Secondary outcomes:
measure: The proportion of evaluable subjects meeting explant criteria and subsequently explanted
timeFrame: 6 weeks, 3, 4, 5, 6, 9, 12-18 months
measure: The time course of reverse remodeling on a left ventricular assist device
timeFrame: 6 weeks, 3, 4, 5, 6, 9, 12-18 months
measure: The time course and sustainability of reverse remodeling following LVAD explantation
timeFrame: 12-18 months
measure: Predictors of recovery and device removal
timeFrame: 6 weeks, 3, 4, 5, 6, 9, 12-18 months
measure: Changes in maximal and sub maximal exercise capacity
timeFrame: 12-18 months
measure: Changes in renal function and hepatic enzymes
timeFrame: 6 weeks, 3, 4, 5, 6, 9, 12-18 months
measure: Changes in EF measured at 6000RPM.
timeFrame: 6 weeks, 4, 6, 9, 12-18 months
measure: Changes in quality of life, as measured by the EuroQoL (EQ5D)
timeFrame: 6 months
Other outcomes:
Locations:
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: New York
country: United States
facility: Montefiore Medical Center
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
Study officials:
affiliation: University of Louisville
name: Emma Birks, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Birks EJ, Drakos SG, Patel SR, Lowes BD, Selzman CH, Starling RC, Trivedi J, Slaughter MS, Alturi P, Goldstein D, Maybaum S, Um JY, Margulies KB, Stehlik J, Cunningham C, Farrar DJ, Rame JE. Prospective Multicenter Study of Myocardial Recovery Using Left Ventricular Assist Devices (RESTAGE-HF [Remission from Stage D Heart Failure]): Medium-Term and Primary End Point Results. Circulation. 2020 Nov 24;142(21):2016-2028. doi: 10.1161/CIRCULATIONAHA.120.046415. Epub 2020 Oct 26.