Remission From Stage D Heart Failure

Heart Failure NYHA Class III Clinical Trial

— RESTAGE-HF  

Official title:

Remission From Stage D Heart Failure (RESTAGE-HF)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01774656
• Other study ID #: RESTAGE-UL
• Status: Recruiting
• Phase: Phase 4
• First received: January 22, 2013
• Last updated: April 25, 2017
• Start date: January 2013
• Est. completion date: December 2017

Study information

• Verified date: April 2017
• Source: University of Louisville
• Contact: Chris Cunningham, PhD
• Email: chris.cunningham[@]louisville.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: December 2017
• Est. primary completion date: December 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 59 Years

Eligibility

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.

Related Conditions & MeSH terms

• Heart Failure
• Heart Failure NYHA Class III
• Heart Failure NYHA Class IV

Intervention

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.

Locations

Country	Name	City	State
United States	Cleveland Clinic	Cleveland	Ohio
United States	University of Louisville	Louisville	Kentucky
United States	Montefiore Medical Center	New York	New York
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	University of Utah	Salt Lake City	Utah

Sponsors (2)

Lead Sponsor	Collaborator
University of Louisville	Thoratec Corporation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of subjects who experience LVAD removal and subsequent freedom from mechanical circulatory support or heart transplantation		12 months
Secondary	The proportion of evaluable subjects meeting explant criteria and subsequently explanted		6 weeks, 3, 4, 5, 6, 9, 12-18 months
Secondary	The time course of reverse remodeling on a left ventricular assist device		6 weeks, 3, 4, 5, 6, 9, 12-18 months
Secondary	The time course and sustainability of reverse remodeling following LVAD explantation		12-18 months
Secondary	Predictors of recovery and device removal		6 weeks, 3, 4, 5, 6, 9, 12-18 months
Secondary	Changes in maximal and sub maximal exercise capacity		12-18 months
Secondary	Changes in renal function and hepatic enzymes		6 weeks, 3, 4, 5, 6, 9, 12-18 months
Secondary	Changes in EF measured at 6000RPM.		6 weeks, 4, 6, 9, 12-18 months
Secondary	Changes in quality of life, as measured by the EuroQoL (EQ5D)		6 months