PMID- 25285748
OWN - NLM
STAT- MEDLINE
DCOM- 20150909
LR  - 20211021
IS  - 1532-8414 (Electronic)
IS  - 1071-9164 (Print)
IS  - 1071-9164 (Linking)
VI  - 21
IP  - 1
DP  - 2015 Jan
TI  - A randomized controlled trial to evaluate the safety and efficacy of cardiac 
      contractility modulation in patients with moderately reduced left ventricular 
      ejection fraction and a narrow QRS duration: study rationale and design.
PG  - 16-23
LID - S1071-9164(14)01221-4 [pii]
LID - 10.1016/j.cardfail.2014.09.011 [doi]
AB  - Cardiac contractility modulation (CCM) signals are nonexcitatory electrical 
      signals delivered during the cardiac absolute refractory period that enhance the 
      strength of cardiac muscular contraction. The FIX-HF-5 study was a prospective 
      randomized study comparing CCM plus optimal medical therapy (OMT) to OMT alone 
      that included 428 New York Heart Association (NYHA) functional class III or IV 
      heart failure patients with ejection fraction (EF) </=45% according to core 
      laboratory assessment. The study met its primary safety end point, but did not 
      reach its primary efficacy end point: a responders analysis of changes in 
      ventilatory anaerobic threshold (VAT). However, in a prespecified subgroup 
      analysis, significant improvements in primary and secondary end points, including 
      the responder VAT end point, were observed in patients with EFs ranging from 25% 
      to 45%, who constituted about one-half of the study subjects. We therefore 
      designed a new study to prospectively confirm the efficacy of CCM in this 
      population. A hierarchic bayesian statistical analysis plan was developed to take 
      advantage of the data already available from the first study. In addition, based 
      on technical difficulties encountered in reliably quantifying VAT and the 
      relatively large amount of nonquantifiable studies, the primary efficacy end 
      point was changed to peak VO2, with significant measures incorporated to minimize 
      the influence of placebo effect. In this paper, we provide the details and 
      rationale of the FIX-HF-5C study design to study CCM plus OMT compared with OMT 
      alone in subjects with normal QRS duration, NYHA functional class III or IV, and 
      EF 25%-45%. This study is registered on www.clinicaltrials.gov with identifier 
      no. NCT01381172.
CI  - Copyright (c) 2015 Elsevier Inc. All rights reserved.
FAU - Abraham, William T
AU  - Abraham WT
AD  - Division of Cardiovascular Medicine, The Ohio State University, Columbus, Ohio.
FAU - Lindenfeld, JoAnn
AU  - Lindenfeld J
AD  - Division of Cardiology, University of Colorado, Denver, Colorado.
FAU - Reddy, Vivek Y
AU  - Reddy VY
AD  - Division of Cardiology, Helmsley Electrophysiology Center, Mount Sinai School of 
      Medicine, New York, New York.
FAU - Hasenfuss, Gerd
AU  - Hasenfuss G
AD  - Department of Cardiology and Pneumology, Georg-August University Goettingen, 
      Goettingen, Germany.
FAU - Kuck, Karl-Heinz
AU  - Kuck KH
AD  - Department of Cardiology, The Asklepios Klinik St. Georg, Hamburg, Germany.
FAU - Boscardin, John
AU  - Boscardin J
AD  - Department of Medicine, University of California San Francisco, San Francisco, 
      California.
FAU - Gibbons, Robert
AU  - Gibbons R
AD  - Department of Health Studies, University of Chicago, Chicago, Illinois.
FAU - Burkhoff, Daniel
AU  - Burkhoff D
AD  - Division of Cardiology, Columbia University, New York, New York. Electronic 
      address: db59@columbia.edu.
CN  - FIX-HF-5C Investigators and Coordinators
LA  - eng
SI  - ClinicalTrials.gov/NCT01381172
GR  - U54 EB020404/EB/NIBIB NIH HHS/United States
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20141005
PL  - United States
TA  - J Card Fail
JT  - Journal of cardiac failure
JID - 9442138
SB  - IM
MH  - Defibrillators, Implantable/adverse effects/*standards
MH  - Female
MH  - Follow-Up Studies
MH  - Heart Failure/diagnosis/physiopathology/*therapy
MH  - *Heart Rate/physiology
MH  - Humans
MH  - *Myocardial Contraction/physiology
MH  - Prospective Studies
MH  - *Stroke Volume/physiology
MH  - Treatment Outcome
MH  - Ventricular Dysfunction, Left/diagnosis/physiopathology/*therapy
PMC - PMC4390995
MID - NIHMS671894
OTO - NOTNLM
OT  - Heart failure
OT  - cardiac resynchronization therapy
OT  - cardiopulmonary stress testing
OT  - quality of life
EDAT- 2014/10/07 06:00
MHDA- 2015/09/10 06:00
PMCR- 2015/04/09
CRDT- 2014/10/07 06:00
PHST- 2014/07/10 00:00 [received]
PHST- 2014/09/26 00:00 [revised]
PHST- 2014/09/29 00:00 [accepted]
PHST- 2014/10/07 06:00 [entrez]
PHST- 2014/10/07 06:00 [pubmed]
PHST- 2015/09/10 06:00 [medline]
PHST- 2015/04/09 00:00 [pmc-release]
AID - S1071-9164(14)01221-4 [pii]
AID - 10.1016/j.cardfail.2014.09.011 [doi]
PST - ppublish
SO  - J Card Fail. 2015 Jan;21(1):16-23. doi: 10.1016/j.cardfail.2014.09.011. Epub 2014 
      Oct 5.