Author + information
- Michael Mielewczik,
- Graham D. Cole,
- Alexandra N. Nowbar,
- Richard Schilling,
- Zachary I. Whinnett,
- Pierre Bordachar,
- Peter Wilmshurst,
- John C. Chambers,
- Brian Olshansky,
- John Morgan,
- Carsten Israel,
- Amarjit S. Sethi,
- Marc van Houwelingen,
- John G. Cleland,
- Georg Schmidt and
- Darrel P. Francis∗
- ↵∗International Centre for Circulatory Health, National Heart and Lung Institute, Imperial College London, 59 North Wharf Road, London W2 1LA, United Kingdom
We read with interest the recent C-CURE (Cardiopoietic stem Cell therapy in heart failURE) trial (1) of stem cells used for the treatment of heart failure. Completing such a multicenter trial is a great achievement, but applying its findings either to clinical care or future trial design might be premature, as there appear to be some inconsistencies in the data. Discrepancies, if left unresolved, can be problematic (2):
• How many patients were randomized? Counts ranged from 45 to 48.
• The authors' corporate website (3) currently states that randomization was 1:1, but Figure 1 in the paper (1) shows counts close to 1:2; conversely, at AHA 2011, the authors said that randomization was 2:1, but reported counts that were close to 1:1. Can the authors please clarify the randomization ratio?
• Once randomized to 1 arm, did any patient's data appear under the heading of the opposite arm? Were some patients allocated to arms by routes other than randomization to those arms? Are baseline characteristics and result data regarding the trial arms, as randomized, available?
• The primary endpoint was pre-specified to be radionuclide ejection fraction, but its results do not appear in the paper. A new primary endpoint is described in the paper. Did all authors agree on this change, and when?
• Regarding the data presented in the paper (1), its Online Appendix, and the previous trial reports (see the Online Appendix for citations), which of these various conflicting versions are correct regarding ejection fraction, end-systolic volume, end-diastolic volume, New York Heart Association functional class, quality of life, and walk distance?
Fewer of certain events, such as arrhythmias, are reported in the current narrative than in previous ones. Could the authors clarify how many stem cell recipients died?
It would be extremely helpful if the authors could resolve these and other uncertainties to aid interpretation (see the Online Appendix for a detailed list of queries, references, and the authors' institutional affiliations).
Please note: Dr. Olshansky is a consultant for BioControl, Medtronic, Boehringer Ingelheim, Daiichi Sankyo, and Boston Scientific; and is on the DSMB for Amarin and Sanofi Aventis. Dr. Cleland has received research grants from Servier, Novartis, Sorin, and Amgen; is on the advisory boards for Amgen, Novartis, Servier, and Respicardia; and speaker fees from Medtronic and Novartis. All other authors have reported that they have no relationships relevant to the contents of this study to report.
- American College of Cardiology Foundation
- Bartunek J.,
- Behfar A.,
- Dolatabadi D.,
- et al.
- ↵Cardio3 Biosciences. Clinical trials. Available at: http://www.c3bs.com/en/clinical-trials. Accessed June 29, 2013.