https://doi.org/10.4081/cardio.2024.18
Clinical trial design, endpoints and regulatory considerations in heart failure
Published: March 28, 2024
Abstract Views: 5131
PDF: 234
HTML: 69
HTML: 69
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.
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.
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
Rosano, G. M. (2024). Clinical trial design, endpoints and regulatory considerations in heart failure. Global Cardiology, 2(1). https://doi.org/10.4081/cardio.2024.18
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
- Elias Tassoulas, Dimitrios Tasoulas, Christos Papaconstantinou, Ioannis Chlorogiannis, Prognostic factors and outcome in patients submitted into coronary artery bypass surgery with total arterial myocardial revascularization , Global Cardiology: Vol. 2 No. 4 (2024)
You may also start an advanced similarity search for this article.
