Multicenter Randomized Controlled Trial of Cardiac Contractility Modulation in Patients with Advanced Heart Failure William T. Abraham MD, Koonlawee Nademanee MD, Kent Volosin MD, Steve Krueger MD, Suresh Neelagaru MD, Nirav Raval MD, Owen Obel MD, Stanley Weiner MD, Mark Wish MD, Peter Carson MD, Kenneth Ellenbogen MD, Robert Bourge MD, Mike Parides MD, Richard P Chiacchierini PhD, Rochelle Goldsmith PhD, Sidney Goldstein MD and Alan Kadish MD on Behalf of the FIX-HF-5 Investigators and Coordinators* *Dr. Abraham and other members of this group have received consulting fees and/or research grants from Impulse Dynamics
26
Embed
Multicenter Randomized Controlled Trial of Cardiac Contractility Modulation in Patients with Advanced Heart Failure
Multicenter Randomized Controlled Trial of Cardiac Contractility Modulation in Patients with Advanced Heart Failure. William T. Abraham MD, Koonlawee Nademanee MD, Kent Volosin MD, Steve Krueger MD, Suresh Neelagaru MD, Nirav Raval MD, Owen Obel MD, Stanley Weiner MD, Mark Wish MD, - PowerPoint PPT Presentation
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
Multicenter Randomized Controlled Trial of Cardiac Contractility Modulation in Patients with Advanced Heart Failure
William T. Abraham MD, Koonlawee Nademanee MD,Kent Volosin MD, Steve Krueger MD, Suresh Neelagaru MD,
Nirav Raval MD, Owen Obel MD, Stanley Weiner MD, Mark Wish MD,Peter Carson MD, Kenneth Ellenbogen MD, Robert Bourge MD,
Mike Parides MD, Richard P Chiacchierini PhD, Rochelle Goldsmith PhD,Sidney Goldstein MD and Alan Kadish MD on Behalf of the FIX-HF-5
Investigators and Coordinators*
*Dr. Abraham and other members of this group have received consulting fees and/or research grants from Impulse Dynamics
Cardiac Contractility Modulation (CCM)Background
• Preclinical and prior clinical studies have demonstrated that CCM:• Increases cardiac contractility• Reduces myocardial work• Produces LV reverse remodeling• Induces molecular changes (in genes,
proteins and phosphorylation) indicative of improved calcium handling and contractile function
The Concept Behind Cardiac Contractility Modulation (CCM)
Detect localactivation
Apply electric signal during absolute refractory period
• First US randomization occurred on April 8, 2005 and the last on June 12, 2007
• Last follow-up completed June 2008
FIX-HF-5: Study Schematic
Informed Consent
Baseline Testing
Eligibility Determination
Group 1 Group 2
12 MonthsCCM 5 hr/day
12 MonthsMedical Control
Device Implantation
2 week Run-In
Study visits at: Baseline, 12Wk, 24Wk and 50Wk
FIX-HF-5: Study Endpoints• Primary Safety Endpoint: Composite of all-cause mortality and
all-cause hospitalization assessed by non-inferiority analysis (active versus control group with 12.5% allowable delta)
• Primary Efficacy Endpoint: Anaerobic Threshold (AT) assessed by responders analysis (≥20% increase in AT = responder)
• Secondary Efficacy Endpoints:• Peak VO2• Minnesota Living with Heart Failure Questionnaire
• Other Efficacy Endpoints• NYHA Functional Class Ranking• 6-Minute Hall Walk Distance
• Subgroup Analyses• Ischemic vs nonischemic• EF above or below the median• NYHA Class III vs IV
Metabolic Exercise Testing and Core Lab• Single core laboratory where a detailed procedure was
followed for objective determination of AT (using the V-slope method) by two independent readers blinded to treatment group
• On-site training on standardized procedures for conducting metabolic exercise tests and electronic data transfer to the core laboratory
• Site revalidation every 6 months• Rapid feedback on test quality from the core laboratory
(on the day the tests were performed)• Despite these efforts, it was anticipated that substantial
number of tests would be classified as indeterminate, either because of poor test quality, inability of subjects to reach AT, or because of poor subject compliance
*P values by one-sided equal varance Student's t-test
Potential Study Limitations
• Choice of anaerobic threshold as a primary endpoint
• Missing VAT data despite rigorous approach to metabolic exercise testing
• Use of responders analyses• Un-implanted control group (no
blinding)
FIX-HF-5: Summary• CCM failed to improve the anaerobic
threshold, pre-specified as the primary endpoint of the trial
• In the overall population, CCM significantly improved
• Peak VO2• Quality of Life (MLWHFQ score)• NYHA
• In a subgroup comprising ~50% of study population (EF≥25, NYHA III), CCM significantly improved
• Peak VO2• AT• MLWHFQ• NYHA
Study Oversight Committees
• Executive Steering Committee• William Abraham, Alan Kadish, Kenneth Ellenbogen,
Robert Bourge, Koonlawee Nademanee, Michael Parides
• Data Safety Monitoring Board• Sidney Goldstein, Steven Gottlieb, Andrea Natale,
David Callans, David Naftel
• Events Adjudication Committee• Peter Carson, Inder Anand, Christopher O’Conner
Study Principal InvestigatorsSuresh Neelagaru, Amarillo, TX Seth Worley, Lancaster, PAAndrew Merliss, Lincoln, NE Roy John, Burlington, MAStanislav Weiner, Tyler, TX David Smull, Winston-Salem, NCJose Joglar, Dallas, TX Raffaele Corbisiero, Trenton, NJNirav Raval, Atlanta, GA Steven Greenberg, Roslyn, NYKoonlawee Nadamanee, Inglewood, CA Mari Rosa Costanzo, Naperville, ILMasood Akhtar, Milwaukee, WI Thomas Mattioni, Scottsdale, AZKent Volosin, Philadelphia, PA Steven Hao, Larkspur, CAFreddy Abi-Samra, New Orleans, LA Mark Wathen, Nashville, TNMarc Wish, Fairfax, VA David Hayes, Rochester, MNImran Niazi, Milwaukee, WI Andrew Cohen, Aurora, COGervasio Lamas, Miami, FL Bengt Herweg, Tampa, FLJavier Sanchez, Austin, TX Harold Goldberg, Spokane, WAEli Gang, Beverly Hills, CA Jill Kalman, New York, NYDavis Baran, Newark, NJ Gregory Jones, Kingsport, TNRandy Lieberman, Detroit, MI Nancy Sweitzer, Madison, WIAlan Bank, St. Paul, MN Mark Wood, Richmond, VAJeffrey Goldberger, Chicago, IL Jonathan Steinberg, New York, NYAllan Murphy, Newport, VA Jose Tallaj, Birmingham, ALJonathan Langberg, Atlanta, GA Alan Heywood, Bellevue, WACharles Love, Columbus, OH Barbara Czerska, Detroit, MIFrank McGrew III, Germantown, TN Gregory Buser, Larkspur, CAHue-The Shih, Houston, TX Steven Klein, Greensboro, NC