TY - JOUR
T1 - End points and clinical trial designs in pulmonary arterial hypertension
T2 - Clinical and regulatory perspectives
AU - Hoeper, Marius M.
AU - Oudiz, Ronald J.
AU - Peacock, Andrew
AU - Tapson, Victor F.
AU - Haworth, Sheila G.
AU - Frost, Adaani E.
AU - Torbicki, Adam
N1 - Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 2004/6/16
Y1 - 2004/6/16
N2 - To date, randomized controlled clinical trials performed in pulmonary arterial hypertension (PAH) have been relatively short-term studies involving mainly patients with advanced disease. The primary end points in these trials have addressed exercise capacity, usually by using the 6-min walk test. Although this approach is still warranted in future trials assessing new treatments, it is likely that the focus will shift toward trials of longer duration, involving patients with less advanced disease, and that different drugs and drug-combination regimens will be compared. In such trials, it is possible that a composite of markers indicating clinical deterioration (e.g., hospitalization for right heart failure, the requirement for the introduction of an alternative treatment, and predefined indicators of worsening exercise tolerance) may be more useful as primary end points. Quality of life will become a very important issue; however, appropriate quality-of-life questionnaires for PAH have yet to be developed. In addition, hemodynamics will likely remain valuable as secondary end points, but future clinical trials should include hemodynamics obtained both during exercise and at rest. Finally, cardiopulmonary exercise testing, echocardiographic studies, and biochemical parameters, such as brain natriuretic peptide or troponin T, may also prove useful as secondary end points in the future.
AB - To date, randomized controlled clinical trials performed in pulmonary arterial hypertension (PAH) have been relatively short-term studies involving mainly patients with advanced disease. The primary end points in these trials have addressed exercise capacity, usually by using the 6-min walk test. Although this approach is still warranted in future trials assessing new treatments, it is likely that the focus will shift toward trials of longer duration, involving patients with less advanced disease, and that different drugs and drug-combination regimens will be compared. In such trials, it is possible that a composite of markers indicating clinical deterioration (e.g., hospitalization for right heart failure, the requirement for the introduction of an alternative treatment, and predefined indicators of worsening exercise tolerance) may be more useful as primary end points. Quality of life will become a very important issue; however, appropriate quality-of-life questionnaires for PAH have yet to be developed. In addition, hemodynamics will likely remain valuable as secondary end points, but future clinical trials should include hemodynamics obtained both during exercise and at rest. Finally, cardiopulmonary exercise testing, echocardiographic studies, and biochemical parameters, such as brain natriuretic peptide or troponin T, may also prove useful as secondary end points in the future.
KW - BNP
KW - CO
KW - CPET
KW - EMEA
KW - European Agency for the Evaluation of Medicinal Products
KW - FDA
KW - Food and Drug Administration
KW - LV
KW - NYHA
KW - New York Heart Association
KW - PAH
KW - brain natriuretic peptide
KW - cardiac output
KW - cardiopulmonary exercise testing
KW - left ventricle/ventricular
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UR - http://www.scopus.com/inward/citedby.url?scp=2942604605&partnerID=8YFLogxK
U2 - 10.1016/j.jacc.2004.02.010
DO - 10.1016/j.jacc.2004.02.010
M3 - Article
C2 - 15194178
AN - SCOPUS:2942604605
VL - 43
SP - S48-S55
JO - Journal of the American College of Cardiology.
JF - Journal of the American College of Cardiology.
SN - 0735-1097
IS - 12 SUPPL.
ER -