Remission From Stage D Heart Failure (RESTAGE-HF)

Remission From Stage D Heart Failure (RESTAGE-HF)

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.

Study Overview

• Status: Unknown
• Conditions: Heart Failure NYHA Class III; Heart Failure NYHA Class IV
• Intervention / Treatment: Drug: Pharmacological Treatment

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 Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 4

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 59 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Proportion of subjects who experience LVAD removal and subsequent freedom from mechanical circulatory support or heart transplantation	12 months

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: University of Louisville
• Collaborators: Thoratec Corporation
• Investigators: Principal Investigator: Emma Birks, MD, University of Louisville

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: January 1, 2013
• Primary Completion (Anticipated): December 1, 2017
• Study Completion (Anticipated): December 1, 2017

Study Registration Dates

• First Submitted: January 22, 2013
• First Submitted That Met QC Criteria: January 22, 2013
• First Posted (Estimate): January 24, 2013

Study Record Updates

• Last Update Posted (Actual): April 27, 2017
• Last Update Submitted That Met QC Criteria: April 25, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: heart-assist device
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: RESTAGE-UL