Editorials
28 March 2024
Vol. 2 No. 1 (2024)
Clinical trial design, endpoints and regulatory considerations in heart failure
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
5547
Views
361
Downloads
69
HTML
Authors
Following the withdrawal of flosequinan in the early 1990s due to heightened mortality and fatal arrhythmia risks, regulatory agencies have demanded evidence of the efficacy of novel treatments in managing heart failure, with mortality and morbidity endpoints becoming more stringent criteria for approval. In recent times, regulatory agencies have exhibited a greater willingness to permit the evaluation of functional capacity as an efficacy endpoint, albeit limited to specific patient groupings. Consequently, a novel therapeutic intervention for heart failure may be granted approval provided that it enhances survival rates, decreases length of hospital stays, and/or safely improves functional capacity. This article reviews clinical trial design, trial endpoints and regulatory issues in heart failure trials.
Altmetrics
Downloads
Download data is not yet available.
Citations
Schüssler-Lenz M, Beuneu C, Menezes-Ferreira M et al. Cell-based therapies for cardiac repair: a meeting report on scientific observations and European regulatory viewpoints. Eur J Heart Fail 2016;18:133-41. DOI: https://doi.org/10.1002/ejhf.422
Anker SD, Schroeder S, Atar D, et al. Traditional and new composite endpoints in heart failure clinical trials: facilitating comprehensive efficacy assessments and improving trial efficiency. Eur J Heart Fail 2016;18:482-9. DOI: https://doi.org/10.1002/ejhf.591
Pani L, Pecorelli S, Rosano G, et al. Steps forward in regulatory pathways for acute and chronic heart failure. Eur J Heart Fail 2015;17:3-8. DOI: https://doi.org/10.1002/ejhf.209
ESC Committee for Practice Guidelines. ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2016: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2016 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail 2016;18:891-975. DOI: https://doi.org/10.1002/ejhf.592
Greene SJ, Shah AN, Butler J, et al. Designing effective drug and device development programs for hospitalized heart failure: a proposal for pretrial registries. Am Heart J 2014;168:142-9. DOI: https://doi.org/10.1016/j.ahj.2014.05.009
Gheorghiade M, Shah AN, Vaduganathan M, et al. Recognizing hospitalized heart failure as an entity and developing new therapies to improve outcomes: academics’, clinicians’, industry’s, regulators’, and payers’ perspectives. Heart Fail Clin 2013;9:285-90. DOI: https://doi.org/10.1016/j.hfc.2013.05.002
Butler J, Fonarow GC, Zile MR, et al. Developing therapies for heart failure with preserved ejection fraction: current state and future directions. JACC Heart Fail 2014;2:97-112. DOI: https://doi.org/10.1016/j.jchf.2013.10.006
Vaduganathan M, Greene SJ, Ambrosy AP, Gheorghiade M, Butler J. The disconnect between phase II and phase III trials of drugs for heart failure. Nat Rev Cardiol 2013;10:85-97. DOI: https://doi.org/10.1038/nrcardio.2012.181
Zannad F, Garcia AA, Anker SD, et al. Clinical outcome endpoints in heart failure trials: a European Society of Cardiology Heart Failure Association consensus document. Eur J Heart Fail. 2013 Oct;15(10):1082-94. DOI: https://doi.org/10.1093/eurjhf/hft095
Fishbein DP, Hellkamp AS, Mark DB, et al. Use of the 6-min walk distance to identify variations in treatment benefits from implantable cardioverterdefibrillator and amiodarone: results from the SCD-HeFT (Sudden Cardiac Death in Heart Failure trial). J Am Coll Cardiol 2014;63:2560-8. DOI: https://doi.org/10.1016/j.jacc.2014.02.602
Seltzer JH, Turner JR, Geiger MJ, et al. Centralized adjudication of cardiovascular endpoints in cardiovascular and noncardiovascular pharmacologic trials: a report from the Cardiac Safety Research Consortium. Am Heart J 2015;169:197-204. DOI: https://doi.org/10.1016/j.ahj.2014.11.003
Collins SP, Pang PS, Fonarow GC, Yancy CW, Bonow RO, Gheorghiade M. Is hospital admission for heart failure really necessary?: the role of the emergency department and observation unit in preventing hospitalization and rehospitalisation. J Am Coll Cardiol 2013;61:121-6. DOI: https://doi.org/10.1016/j.jacc.2012.08.1022
Harinstein ME, Butler J, Greene SJ, et al. Site selection for heart failure clinical trials in the USA. Heart Fail Rev 2015;20:375-83. DOI: https://doi.org/10.1007/s10741-015-9473-z
Rosano GM, Anker SD, Marrocco W, Coats AJ. Adaptive licensing. A way forward in the approval process of new therapeutic agents in Europe. Int J Cardiol 2015;184:568-9. DOI: https://doi.org/10.1016/j.ijcard.2015.02.112
Pelliccia F, Rosano GM. Back to the future: the crucial role of clinical registries in the era of randomized controlled trials for identifying the optimal medical therapy of heart failure. Eur Heart J Cardiovasc Pharmacother 2015;1:37-8. DOI: https://doi.org/10.1093/ehjcvp/pvu015
Capuano A, Coats AJ, Scavone C, Rossi F, Rosano GM. Disclosure of negative trial results. A call for action. Int J Cardiol 2015;198:47-8. DOI: https://doi.org/10.1016/j.ijcard.2015.06.157
How to Cite
1.
Rosano GM. Clinical trial design, endpoints and regulatory considerations in heart failure. Global Cardiol [Internet]. 2024 Mar. 28 [cited 2025 Aug. 12];2(1). Available from: https://www.globalcardiology.info/site/article/view/18
Copyright (c) 2024 the Author(s)
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
PAGEPress has chosen to apply the Creative Commons Attribution NonCommercial 4.0 International License (CC BY-NC 4.0) to all manuscripts to be published.
Similar Articles
- Stefan D. Anker, Javed Butler, Khawaja M. Talha, Tim Friede, Using multiple primary endpoints in clinical trials with a focus on heart failure , Global Cardiology: Vol. 2 No. 2 (2024)
- Ralph Stephan von Bardeleben, Muhammad Shahzeb Khan, Martin Geyer, Tim Friede, Javed Butler, Monika Diek, Jutta Heinrich, Marius Placzek, Roberto Ferrari, William T. Abraham, Ottavio Alfieri, Angelo Auricchio, Antoni Bayes-Genis, John G.F. Cleland, Gerasimos Filippatos, Finn Gustafsson, Wilhelm Haverkamp, Malte Kelm, Karl-Heinz Kuck, Ulf Landmesser, Aldo P. Maggioni, Marco Metra, Vlasis Ninios, Mark C. Petrie, Tienush Rassaf, Frank Ruschitzka, Ulrich Schäfer, P. Christian Schulze, Konstantinos Spargias, Alec Vahanian, Jose Luis Zamorano, Andreas Zeiher, Mahir Karakas, Friedrich Koehler, Mitja Lainscak, Alper Öner, Nikolaos Mezilis, Efstratios K. Theofilogiannakos, Ilias Ninios, Michael Chrissoheris, Panagiota Kourkoveli, Konstantinos Papadopoulos, Grzegorz Smolka, Wojciech Wojakowski, Krzysztof Reczuch, Fausto J. Pinto, Łukasz Wiewiórka, Zbigniew Kalarus, Marianna Adamo, Evelyn Santiago-Vacas, Tobias Friedrich Ruf, Michael Gross, Joern Tongers, Gerd Hasenfuß, Wolfgang Schillinger, Piotr Ponikowski, Stefan D. Anker, Baseline echocardiographic characteristics of patients enrolled in the randomized investigation of MitraClip device in heart failure (RESHAPE HF-2) trial: comparison with COAPT and Mitra-FR , Global Cardiology: Vol. 2 No. 2 (2024)
- Marc Atzenhoefer, Elizabeth Dille, Rebecca Steinke, Nicole Weigert, Keri Sabel, Kirsten Rasmussen, Bridging the gap between study outcomes and real-world results. Algorithm-driven management in a rural cardioMEMS population , Global Cardiology: Vol. 3 No. 1 (2025)
- Laibah Arshad Khan, Muhammad Shahzeb Khan, Rania Usman Latif, Markus S. Anker, Cardiac wasting in patients with advanced cancer: state of the art review , Global Cardiology: Vol. 3 No. 1 (2025)
- Muhammad Shariq Usman, Arsalan Hamid, Shurjeel Uddin Qazi, Mikhail N. Kosiborod, Deepak L. Bhatt, Muhammad Shahzeb Khan, Muthiah Vaduganathan, Javed Butler, The effect of SGLT2 inhibitors on health status in patients with heart failure: a systematic review and meta-analysis , Global Cardiology: Vol. 2 No. 2 (2024)
- Wardah Rasool, Ahmed Kamal Siddiqi, Laibah Arshad Khan, Importance of patient-reported outcomes in cardiovascular illnesses , Global Cardiology: Vol. 3 No. 2 (2025)
- Javed Butler, Sanjiv J. Shah, Melissa Magwire, Carlos Campos, Muhammad Shariq Usman, Anthony Hoovler, Anup Sabharwal, Barry A. Borlaug, Treatment pathways in patients with heart failure with preserved ejection fraction and obesity: perspectives from cardiology specialists and patients , Global Cardiology: Vol. 2 No. 2 (2024)
- Tarek Bekfani, Kris G. Vargas, Flor Gomez, Alexander Schmeisser, Ruediger C. Braun-Dullaeus, The effect of sauna on cardiac and skeletal muscle function in patients with HFpEF (SAUNA-HFpEF): rationale and design , Global Cardiology: Vol. 3 No. 2 (2025)
- Stephan von Haehling, Wolfram Doehner, Ruben Evertz, Tania Garfias-Veitl, Monika Diek, Mahir Karakas, Ralf Birkemeyer, Gerasimos Fillippatos, Piotr Ponikowski, Michael Böhm, Tim Friede, Stefan D. Anker, Iron deficiency in heart failure with preserved ejection fraction: rationale and design of the FAIR-HFpEF trial , Global Cardiology: Vol. 1 No. 1 (2023)
- Natasa Sedlar Kobe, Daniel Omersa, Mitja Lainscak, Jerneja Farkas, Depression, health-related quality of life and life satisfaction in patients with heart failure , Global Cardiology: Vol. 2 No. 3 (2024)
1-10 of 63
Next
You may also start an advanced similarity search for this article.
