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Remission From Stage D Heart Failure (RESTAGE-HF)

Primary Purpose

Heart Failure NYHA Class III, Heart Failure NYHA Class IV

Status

Unknown status

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

Pharmacological Treatment

About this trial

This is an interventional treatment trial for Heart Failure NYHA Class III focused on measuring heart-assist device

Eligibility Criteria

18 Years - 59 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

Subject has evidence of active acute myocarditis confirmed by histology
Subject has a history of previous CVA resulting in significant fixed motor deficit limiting ability to perform exercise testing
Subject has been implanted with a mechanical aortic and/or mitral valve(s)
Subject had an aortic valve closure
Subject diagnosed with a hypertrophic obstructive cardiomyopathy or sarcoidosis
Subject with LVEDD below normal confirmed by surface echocardiogram (restrictive cardiomyopathy)
Subject has irreversible multi-organ failure
Pregnant or lactating women or unwilling to utilize two reliable methods of birth control for women of childbearing age
Subject is diagnosed with a psychiatric disease, irreversible cognitive dysfunction or poor psychosocial issues that is likely to impair compliance with the study protocol
Subject with any condition, other than heart failure, that could limit survival to less than 2 years
Subject has a history of cardiac or other organ transplant
Subject is contraindicated to anticoagulation antiplatelet therapy
Subject requires acute or chronic renal replacement therapy (e.g. chronic dialysis) within 3 months prior to enrollment
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.

Sites / Locations

University of LouisvilleRecruiting
University of Nebraska Medical CenterRecruiting
Montefiore Medical CenterRecruiting
Cleveland ClinicRecruiting
University of PennsylvaniaRecruiting
University of UtahRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

HeartMate II plus Pharmacological Treat

Arm Description

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.

Outcomes

Primary Outcome Measures

Proportion of subjects who experience LVAD removal and subsequent freedom from mechanical circulatory support or heart transplantation

Secondary Outcome Measures

The proportion of evaluable subjects meeting explant criteria and subsequently explanted

The time course of reverse remodeling on a left ventricular assist device

The time course and sustainability of reverse remodeling following LVAD explantation

Predictors of recovery and device removal

Changes in maximal and sub maximal exercise capacity

Changes in renal function and hepatic enzymes

Changes in EF measured at 6000RPM.

Changes in quality of life, as measured by the EuroQoL (EQ5D)

Full Information

NCT ID

NCT01774656

First Posted

January 22, 2013

Last Updated

April 25, 2017

Sponsor

University of Louisville

Collaborators

Thoratec Corporation

1. Study Identification

Unique Protocol Identification Number

NCT01774656

Brief Title

Remission From Stage D Heart Failure

Acronym

RESTAGE-HF

Official Title

Remission From Stage D Heart Failure (RESTAGE-HF)

Study Type

Interventional

2. Study Status

Record Verification Date

April 2017

Overall Recruitment Status

Unknown status

Study Start Date

January 2013 (undefined)

Primary Completion Date

December 2017 (Anticipated)

Study Completion Date

December 2017 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of Louisville

Collaborators

Thoratec Corporation

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Heart Failure NYHA Class III, Heart Failure NYHA Class IV

Keywords

heart-assist device

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

HeartMate II plus Pharmacological Treat

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Pharmacological Treatment

Intervention Description

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.

Primary Outcome Measure Information:

Title

Proportion of subjects who experience LVAD removal and subsequent freedom from mechanical circulatory support or heart transplantation

Time Frame

12 months

Secondary Outcome Measure Information:

Title

The proportion of evaluable subjects meeting explant criteria and subsequently explanted

Time Frame

6 weeks, 3, 4, 5, 6, 9, 12-18 months

Title

The time course of reverse remodeling on a left ventricular assist device

Time Frame

6 weeks, 3, 4, 5, 6, 9, 12-18 months

Title

The time course and sustainability of reverse remodeling following LVAD explantation

Time Frame

12-18 months

Title

Predictors of recovery and device removal

Time Frame

6 weeks, 3, 4, 5, 6, 9, 12-18 months

Title

Changes in maximal and sub maximal exercise capacity

Time Frame

12-18 months

Title

Changes in renal function and hepatic enzymes

Time Frame

6 weeks, 3, 4, 5, 6, 9, 12-18 months

Title

Changes in EF measured at 6000RPM.

Time Frame

6 weeks, 4, 6, 9, 12-18 months

Title

Changes in quality of life, as measured by the EuroQoL (EQ5D)

Time Frame

6 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

59 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Subject age between 18 - 59 years, inclusive Subject indicated for DT or BTT Subject with severe clinical heart failure resistant to intensive medical therapy and requiring LVAD implantation Subject with LVEF < 25% and cardiomegaly at the time of LVAD implantation as documented by radionuclide or contrast ventriculography or by echocardiography Subject with non-ischemic etiology (confirmed by angiography either within 2 years of implantation or prior to explantation) Subject have undergone HM II implantation within prior 4 weeks or planned for a HM II implant Subject has a history of HF < 5 years. Exclusion Criteria: Subject has evidence of active acute myocarditis confirmed by histology Subject has a history of previous CVA resulting in significant fixed motor deficit limiting ability to perform exercise testing Subject has been implanted with a mechanical aortic and/or mitral valve(s) Subject had an aortic valve closure Subject diagnosed with a hypertrophic obstructive cardiomyopathy or sarcoidosis Subject with LVEDD below normal confirmed by surface echocardiogram (restrictive cardiomyopathy) Subject has irreversible multi-organ failure Pregnant or lactating women or unwilling to utilize two reliable methods of birth control for women of childbearing age Subject is diagnosed with a psychiatric disease, irreversible cognitive dysfunction or poor psychosocial issues that is likely to impair compliance with the study protocol Subject with any condition, other than heart failure, that could limit survival to less than 2 years Subject has a history of cardiac or other organ transplant Subject is contraindicated to anticoagulation antiplatelet therapy Subject requires acute or chronic renal replacement therapy (e.g. chronic dialysis) within 3 months prior to enrollment 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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Chris Cunningham, PhD

chris.cunningham@louisville.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Emma Birks, MD

Organizational Affiliation

University of Louisville

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Louisville

City

Louisville

State/Province

Kentucky

ZIP/Postal Code

40202

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Terry Blanton, BSN, RN

mtblan02@louisville.edu

First Name & Middle Initial & Last Name & Degree

Emma Birks, MD, PhD

Facility Name

University of Nebraska Medical Center

City

Omaha

State/Province

Nebraska

ZIP/Postal Code

68198

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Stacy Flickbohm, RN

Phone

402-559-5127

stacy.fickbohm@unmc.edu

First Name & Middle Initial & Last Name & Degree

Natalie Kamtz

Phone

402-559-3293

natalie.kamtz@unmc.edu

First Name & Middle Initial & Last Name & Degree

Brian D Lowes, MD, PhD

Facility Name

Montefiore Medical Center

City

New York

State/Province

New York

ZIP/Postal Code

10467

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Auris Brown

aubrowne@montefiore.org

First Name & Middle Initial & Last Name & Degree

Johanna Oviedo

Phone

718-920-8780

joviedo@montefiore.org

First Name & Middle Initial & Last Name & Degree

Snehal Patel, MD

Facility Name

Cleveland Clinic

City

Cleveland

State/Province

Ohio

ZIP/Postal Code

44195

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Barb Gus, RN BSN CCRC

Phone

216-445-6552

GUSB@ccf.org

First Name & Middle Initial & Last Name & Degree

Maria Mountis, D.O.

Facility Name

University of Pennsylvania

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19140

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Judith Marble

Judith.Marble@uphs.upenn.edu

First Name & Middle Initial & Last Name & Degree

J E Rame, MD

Facility Name

University of Utah

City

Salt Lake City

State/Province

Utah

ZIP/Postal Code

84112

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Ashley Elmer

ashley.elmer@hsc.utah.edu

First Name & Middle Initial & Last Name & Degree

Craig Selzman, MD

12. IPD Sharing Statement

Citations:

PubMed Identifier

33100036

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.

Results Reference

derived

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Remission From Stage D Heart Failure

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