The Randomized Evaluation of VAD InterVEntion Before Inotropic Therapy (REVIVE-IT)

This study has suspended participant recruitment.
(Clinical Hold)
Sponsor:
Collaborators:
Thoratec Corporation
Information provided by (Responsible Party):
Francis D. Pagani, University of Michigan
ClinicalTrials.gov Identifier:
NCT01369407
First received: June 1, 2011
Last updated: January 30, 2015
Last verified: January 2015
  Purpose

This is a randomized trial of the HeartMate II® Left Ventricular Assist System (LVAS) versus best medical therapy in patients with advanced heart failure (HF) and whose illness is not severe enough to qualify for transplant or permanent left ventricular assist device (LVAD) therapy based on current guidelines.


Condition Intervention Phase
Congestive Heart Failure
Device: HM II® (HeartMate II® LVAD)
Other: OMM (Optimal Medical Management)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: The Randomized Evaluation of VAD InterVEntion Before Inotropic Therapy (REVIVE-IT)

Resource links provided by NLM:


Further study details as provided by University of Michigan:

Primary Outcome Measures:
  • Composite outcome of Survival, Freedom from moderately disabling stroke (defined as Modified Rankin Scale (MRS) ≥ 3) and Improvement of 6 Minute Walk Test distance by ≥75 meters from pre-randomization baseline. [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Moderately disabling (MRS ≥3) stroke-free survival with functional improvement of the 6 Minute Walk Test distance by ≥ 75 meters from pre-randomization baseline evaluated at 1 year [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Functional capacity [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Assessed by: 6 Minute Walk test, peak oxygen consumption, % predicted peak V02, oxygen uptake efficiency slope, VE/VCO2 slope, anaerobic threshold, NYHA functional class

  • Health-related Quality of Life and Health Utility [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Assessed by completion of various instruments

  • Neurocognition [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Heart failure-related adverse events [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    Worsening heart failure resulting in non-elective hospitalization, emergency department visit, urgent clinic visit at which intravenous therapy is administered.

  • Hospital Readmission [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Cost and cost-effectiveness [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Major adverse events (as defined in the protocol) in LVAD and OMM arms [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Frequency of "Change of Therapy" to LVAD in the OMM arm [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Frequency of heart transplantation in the OMM and LVAD arms [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Moderately disabling (MRS ≥3) stroke-free survival with functional improvement of the 6 Minute Walk Test distance by ≥75 m from pre-randomization baseline evaluated after consideration of "positive" and "negative" events. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Moderately disabling (MRS ≥3) stroke-free survival with functional improvement of the 6 Minute Walk Test distance by ≥ 75 meters from pre-randomization baseline evaluated after adjusted for within site correlation [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Enrollment feasibility [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Stroke/TIA [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    Incidence of stroke

  • Survival [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Moderately disabling (MRS ≥3) stroke-free survival with functional improvement of the 6 Minute Walk Test distance by ≥75 m from pre-randomization baseline evaluated after consideration of "positive" and "negative" events. [ Time Frame: 1 years ] [ Designated as safety issue: No ]
  • Moderately disabling (MRS ≥3) Stroke- free days alive out of the hospital (from time of enrollment) [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Stroke-free days (MRS=0) alive out of the hospital (from time of enrollment) [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 100
Study Start Date: August 2013
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: HM II® (HeartMate II® LVAD)
Implantation of HM II® (HeartMate II® LVAD)
Device: HM II® (HeartMate II® LVAD)
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.
Other Name: Left Ventricular Assist Device
OMM (Optimal Medical Management )
OMM (Optimal Medical Management) as defined by current, evidenced-based heart failure practice standards including ACE inhibitors or ARB, a beta blocker and an aldosterone antagonists.
Other: OMM (Optimal Medical Management)
Optimal Medical Management as defined by current, evidenced-based heart failure practice standards including ACE inhibitors or ARB, a beta blocker and an aldosterone antagonists.
Other Name: Medical Management

Detailed Description:

REVIVE-IT is a two-part study consisting of a trial and a registry. The REVIVE-IT Trial is a prospective, randomized, open-label, multicenter trial, evaluating the HeartMate II® LVAS versus a control group consisting of optimal medical management (OMM) in selected non-inotrope dependent, ambulatory, moderately advanced heart failure patients who are not candidates for heart transplantation based upon assessment of comorbidities and age.

Patients are randomized to HeartMate II® LVAS or OMM in a 1:1 ratio and will be followed for 2 years. A staged enrollment plan will be used to ensure the safety of the study subjects receiving the HeartMate II® LVAS.

Patients will be entered into a prospective, observational, multi-center registry to collect information on heart failure and to evaluate how this information is related to the course of the illness over a 2 to 5 year period.

  Eligibility

Ages Eligible for Study:   21 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Ambulatory patient with chronic systolic heart failure ( documented HF symptoms ≥ 12 months; last documented LVEF ≤ 35%) and:

    1. Stable predominantly NYHA class III symptoms for the 3 months prior to study enrollment and up through randomization
    2. Receiving maximally-titrated doses of an ACE inhibitor or ARB, a beta-blocker and aldosterone antagonist, and, for African American patients, hydralazine and either isosorbide dinitrate or isosorbide mononitrate for at least 3 months prior to study enrollment, unless not tolerated or contraindicated; doses of these medications must be stable
    3. ≤ 2 heart failure-related hospitalization within the previous 6 months, with no heart failure-related hospitalization occurring within the 30 days prior to study enrollment and up through randomization
    4. No history of intravenous inotrope use within the 30 days prior to study enrollment and up through randomization; any intravenous inotrope use 31-90 days prior to study enrollment must be limited to ≤ 24 hours
  2. Age ≥ 21 years
  3. CRT/ICD entry criteria:

    1. If QRS duration ≥ 150 msec, in the presence of a left bundle branch block, the patient must have a CRT-D device (unless at least 1 prior attempt failed or compelling clinical contraindication, in which case patient must have an ICD)
    2. Patients who qualify for CRT or CRT-D must have it for ≥ 90 days prior to study enrollment
    3. If QRS duration < 150 msec, patient must have an ICD
    4. Patients who qualify for ICD must have it for ≥ 30 days prior to study enrollment
  4. BSA ≥ 1.2 m2
  5. Not a candidate for heart transplantation as determined by the Clinical Site Heart Transplant Committee
  6. LVEF ≤35% by transthoracic echocardiogram
  7. Peak exercise oxygen consumption is ≤ 14 ml/Kg/min by cardiopulmonary exercise testing
  8. 6 Minute Walk Test distance is ≤ 350 meters
  9. Low risk for right heart failure

Exclusion Criteria:

  1. Patient unable or unwilling to give informed consent or with high risk of noncompliance with study requirements
  2. Ongoing alcohol or drug abuse
  3. Participation in any other investigational study that may affect the outcome of the REVIVE-IT Trial
  4. Severe illness, other than heart disease, that would limit the patient's life expectancy to less than 2 years
  5. Acute STEMI within 3 months prior to study enrollment or between enrollment and randomization
  6. Pregnant females or women of child bearing-age who are not willing to use contraception
  7. Patient with a Body Mass Index > 45 kg/m2
  8. Any condition other than heart failure (e.g., arthritic, orthopedic, neuromuscular, neurologic) that is likely to substantially impair ability to achieve study's exercise endpoint
  9. Existence of any ongoing mechanical circulatory support including intra-aortic balloon counterpulsation, implantable or extracorporeal ventricular assist device, or ECMO
  10. Contraindication or intolerance to use of warfarin or antiplatelet therapies
  11. History of a solid organ transplant or currently listed for a solid organ transplant including heart transplantation
  12. Patients with mechanical prosthetic aortic valve or requiring planned aortic valve replacement or closure of the aortic valve annulus at the time of LVAD surgery
  13. Patients with mechanical prosthetic mitral valve or requiring planned mitral valve procedure at the time of LVAD surgery.
  14. Etiology of heart failure due to hypertrophic cardiomyopathies, restrictive cardiomyopathies, constrictive pericardial disease, amyloidosis, active myocarditis, uncorrected thyroid disease, congenital heart disease with significant structural abnormalities
  15. Medical conditions or technical obstacles that would pose an inordinately high surgical risk in the judgment of the certified surgeon
  16. Active systemic infection
  17. Significant history of cerebral vascular disease
  18. Significant renal dysfunction
  19. Significant liver dysfunction
  20. Serum albumin < 3.0 g/dl
  21. Patients at risk of coagulopathy
  22. Significant pulmonary disease
  23. Peripheral vascular disease
  24. Evidence of any of the following on the study echocardiogram

    1. left atrial or left ventricular thrombus
    2. significant calcification on the left ventricular apex
    3. left ventricular end-diastolic dimension of ≤ 55 mm
  25. Patients with hypercoagulable disorders or at high risk of having hypercoagulable disorder
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01369407

  Show 21 Study Locations
Sponsors and Collaborators
University of Michigan
Thoratec Corporation
Investigators
Principal Investigator: Keith Aaronson, MD, MS University of Michigan
Principal Investigator: Francis D Pagani, MD PhD University of Michigan
Principal Investigator: Robert Kormos, MD University of Pittsburgh
Study Chair: Doug Mann, MD University of Washington - St. Louis
  More Information

Additional Information:
No publications provided

Responsible Party: Francis D. Pagani, Professor of Surgery, University of Michigan
ClinicalTrials.gov Identifier: NCT01369407     History of Changes
Other Study ID Numbers: REVIVE-IT, HHSN268201100026C
Study First Received: June 1, 2011
Last Updated: January 30, 2015
Health Authority: United States: Data and Safety Monitoring Board
United States: Federal Government
United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by University of Michigan:
Heart failure
HF
Heart Diseases
Cardiovascular Diseases
left ventricular assist device
LVAD
ventricular dysfunction
heart-assist devices
ventricular assist device
optimal medical management
HeartMate II
medical management
Heart Failure NYHA class III

Additional relevant MeSH terms:
Heart Failure
Cardiovascular Diseases
Heart Diseases

ClinicalTrials.gov processed this record on April 27, 2015