TY - JOUR
T1 - Phase II trials in heart failure
T2 - The role of cardiovascular imaging
AU - Shah, Sanjiv J.
AU - Fonarow, Gregg C.
AU - Gheorghiade, Mihai
AU - Lang, Roberto M.
N1 - Funding Information:
Dr Shah reports receiving research grants from the American Heart Association, American Society of Echocardiography, Heart Failure Society of America, Northwestern Memorial Foundation, Actelion, and Gilead. Dr Fonarow reports receiving research grants from the National Institutes of Health; being a consultant for Medtronic, Novartis, and Scios; and receiving honoraria from Medtronic. He holds the Eliot Corday Chair in Cardiovascular Medicine and Science and is also supported by the Ahmanson Foundation (Los Angeles, CA). Dr Gheorghiade reports being a consultant for Otsuka, Merck, Scios, Debiopharm, Errekappa Terapeutici, GlaxoSmithKline, Bayer, Novartis, Takeda, Johnson & Johnson, Travena, Protein Design Laboratories, Medtronic, and Sigma-Tau; and receiving honoraria from Abbott, AstraZeneca, GlaxoSmithKline, Medtronic, Otsuka, Protein Design Laboratories, Scios, and Sigma-Tau. Dr Lang has no disclosures. No extramural funding was used to support this work. The authors are solely responsible for the design and conduct of this manuscript, all analyses, the drafting and editing of the manuscript, and its final contents.
PY - 2011/7
Y1 - 2011/7
N2 - The development of new therapies for heart failure (HF), especially acute HF, has proven to be quite challenging; and therapies evaluated in HF have greatly outnumbered treatments that are eventually successful in obtaining regulatory approval. Thus, the development of therapies for HF remains a vexing problem for pharmaceutical and device companies, clinical trialists, and health care professionals. Nowhere is this more apparent than in the phase II HF clinical trial, in which the goal is to determine whether an investigational agent should move forward to a phase III trial. Recent advancements in noninvasive cardiovascular imaging have allowed a new era of comprehensive phenotyping of cardiac structure and function in phase II HF trials. Besides using imaging parameters to predict success of subsequent phase III outcome studies, it is essential to also use imaging in phase II HF trials in a way that increases understanding of drug or device mechanism. Determination of the patients who would benefit most from a particular drug or device could decrease heterogeneity of phase III trial participants and lead to more successful HF clinical trials. In this review, we outline advantages and disadvantages of imaging various aspects of cardiac structure and function that are potential targets for therapy in HF, compare and contrast imaging modalities, provide practical advice for the use of cardiovascular imaging in drug development, and conclude with some novel uses of cardiac imaging in phase II HF trials.
AB - The development of new therapies for heart failure (HF), especially acute HF, has proven to be quite challenging; and therapies evaluated in HF have greatly outnumbered treatments that are eventually successful in obtaining regulatory approval. Thus, the development of therapies for HF remains a vexing problem for pharmaceutical and device companies, clinical trialists, and health care professionals. Nowhere is this more apparent than in the phase II HF clinical trial, in which the goal is to determine whether an investigational agent should move forward to a phase III trial. Recent advancements in noninvasive cardiovascular imaging have allowed a new era of comprehensive phenotyping of cardiac structure and function in phase II HF trials. Besides using imaging parameters to predict success of subsequent phase III outcome studies, it is essential to also use imaging in phase II HF trials in a way that increases understanding of drug or device mechanism. Determination of the patients who would benefit most from a particular drug or device could decrease heterogeneity of phase III trial participants and lead to more successful HF clinical trials. In this review, we outline advantages and disadvantages of imaging various aspects of cardiac structure and function that are potential targets for therapy in HF, compare and contrast imaging modalities, provide practical advice for the use of cardiovascular imaging in drug development, and conclude with some novel uses of cardiac imaging in phase II HF trials.
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U2 - 10.1016/j.ahj.2011.03.031
DO - 10.1016/j.ahj.2011.03.031
M3 - Review article
C2 - 21742085
AN - SCOPUS:79960190946
VL - 162
SP - 3-15.e3
JO - American Heart Journal
JF - American Heart Journal
SN - 0002-8703
IS - 1
ER -