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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by University of Michigan
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: August 19, 2014
Last verified: August 2014
  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, 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 inotrope use within the 3 months prior to study enrollment and up through randomization
  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 ≥ 30% and ≤ 50% of predicted and ≤ 16 ml/Kg/min in males or ≤ 14 ml/Kg/min in females by cardiopulmonary exercise testing
  8. 6 Minute Walk Test distance is ≤ 300 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

Contacts
Contact: Huwaida B. Betts, MBChB, MPH 734-763-0597 huwaidab@umich.edu

Locations
United States, Alabama
University of Alabama - (Birmingham) Recruiting
Birmingham, Alabama, United States, 35294
Contact: Gina Horton    205-975-8511    ghorton@uab.edu   
Principal Investigator: Salpy Pamboukian, MD         
Principal Investigator: William Holman, MD         
United States, Georgia
Emory University Not yet recruiting
Atlanta, Georgia, United States, 30322
Contact: Jayne Thompson, RN    404-778-4920    sjdanle@emory.edu   
Principal Investigator: Sonjoy Laskar, MD         
Principal Investigator: J. David Vega, MD         
United States, Illinois
University of Chicago Recruiting
Chicago, Illinois, United States, 60637
Contact: Becki Pisarski, RN    773-834-3791    bpisarski@surgery.bsd.uchicago.edu   
Principal Investigator: Savitri Fedson, MD         
Principal Investigator: Valluvan Jeevanandam, MD         
Advocate Christ Medical Center Recruiting
Oak Lawn, Illinois, United States, 60453
Contact: Colleen Gallagher, BSN    708-684-9699 ext 133    colleen.gallagher@advocatehealth.com   
Principal Investigator: William Cotts, MD         
Principal Investigator: Antone Tatooles, MD         
United States, Indiana
St. Vincent Heart Center of Indiana Not yet recruiting
Indianapolis, Indiana, United States, 46260
Contact: Regina Margiotti    317-338-6151    RAMARGIO@stvincent.org   
Principal Investigator: Mary Norine Walsh, MD, FACC         
Principal Investigator: Christopher Salerno, MD         
United States, Kentucky
University of Louisville Recruiting
Louisville, Kentucky, United States, 40202
Contact: Terry Blanton, BSN, RN, PCCN    502-587-4381    mtblan02@louisville.edu   
Principal Investigator: Emma Birks, MD, PhD         
Principal Investigator: Mark Slaughter, MD         
United States, Michigan
University of Michigan Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Neha Shah    734-232-4606    neshah@umich.edu   
Principal Investigator: Todd Koelling, MD         
Principal Investigator: Matthew Romano         
United States, Minnesota
Minneapolis Heart Institute Foundation Recruiting
Minneapolis, Minnesota, United States, 55407
Contact: Sarah O Smith    612-863-6286    Sarah.Smith2@allina.com   
Principal Investigator: David Feldman, MD, PhD         
Principal Investigator: Louis B Louis, IV, MD         
University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55944
Contact: Carol Toninato, RN, BSN    612-273-4779    ctoninato@umphysicians.umn.edu   
Principal Investigator: Peter Eckman, MD         
Principal Investigator: Ranjit John, MD         
United States, Missouri
Washington University Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Donna Whitehead, RN    314-454-7422    dwhitehe@wustl.edu   
Principal Investigator: Gregory Ewald, MD         
Principal Investigator: Scott Silvestry, MD         
United States, New York
Montefiore Medical Center Recruiting
Bronx, New York, United States, 10467
Contact: Johanna Oviedo    718-920-8780    joviedo@montefiore.org   
Principal Investigator: J. Julia Shin, MD         
Principal Investigator: Daniel Goldstein, MD         
Columbia University Recruiting
New York, New York, United States, 10032
Contact: Kyusun Cha    212-342-2104    kc2889@cumc.columbia.edu   
Principal Investigator: Ulrich Jorde, MD         
Principal Investigator: Yoshifumi Naka, MD, PhD         
University of Rochester Not yet recruiting
Rochester, New York, United States, 14642
Contact: Colleen Patterson    585-273-5247    Colleen_Patterson@URMC.Rochester.edu   
Principal Investigator: Leway Chen, MD, MPH         
Principal Investigator: Howard Todd Massey, MD         
United States, Oklahoma
INTEGRIS Health Advanced Cardiac Care Recruiting
Oklahoma, Oklahoma, United States, 73112
Contact: Mandy Williams    405-951-8217    mandy.williams@integrisok.com   
Principal Investigator: James Long, MD, PhD         
Principal Investigator: Douglas Horstmanshof, MD         
United States, Pennsylvania
University of Pennsylvania Not yet recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Judy Marble, RN       Judith.Marble@uphs.upenn.edu   
Principal Investigator: J. Eduardo Rame, MD         
Principal Investigator: Michael Acker, MD         
University of Pittsburgh Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: Jessica Pisarcik, RN, BSN    412-647-4463    pisarcikje2@upmc.edu   
Principal Investigator: Jeffrey J Teuteberg, MD         
Principal Investigator: Christian Bermudez, MD         
United States, Texas
The Methodist Hospital Recruiting
Houston, Texas, United States, 77030
Contact: Eunice Karanja, RN    713-441-3571    ekaranja@houstonmethodist.org   
Principal Investigator: Jerry Estep, MD         
Principal Investigator: Brian Bruckner, MD         
United States, Utah
University of Utah Not yet recruiting
Salt Lake City, Utah, United States, 84054
Contact: Jeff Gibbs    801-585-3188    Jeffrey.Gibbs@hsc.utah.edu   
Principal Investigator: Josef Stehlik         
Principal Investigator: Craig Selzman, MD         
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: August 19, 2014
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
Heart Diseases
left ventricular assist device
ventricular dysfunction
heart-assist devices
ventricular assist device
Heart Failure NYHA class III
HF
Cardiovascular Diseases
LVAD
optimal medical management
HeartMate II
medical management

Additional relevant MeSH terms:
Heart Failure
Cardiovascular Diseases
Heart Diseases

ClinicalTrials.gov processed this record on November 25, 2014