End points and clinical trial design in pulmonary arterial hypertension

Vallerie V McLaughlin; David B Badesch; Marion Delcroix; Thomas R Fleming; Sean P Gaine; Nazzareno Galiè; J Simon R Gibbs; Nick H Kim; Ronald J Oudiz; Andrew Peacock; Steeve Provencher; Olivier Sitbon; Victor F Tapson; Werner Seeger

doi:10.1016/j.jacc.2009.04.007

End points and clinical trial design in pulmonary arterial hypertension

J Am Coll Cardiol. 2009 Jun 30;54(1 Suppl):S97-S107. doi: 10.1016/j.jacc.2009.04.007.

Authors

Affiliations

¹ Department of Internal Medicine, University of Michigan Health System, Ann Arbor, Michigan. Electronic address: vmclaugh@med.umich.edu.
² Divisions of Pulmonary Sciences and Critical Care Medicine, and Cardiology, University of Colorado Health Sciences Center, Denver, Colorado.
³ Center for Pulmonary Vascular Disease, Department of Pneumology, Gasthuisberg University Hospital, Leuven, Belgium.
⁴ Department of Biostatistics, University of Washington, Seattle, Washington.
⁵ National Pulmonary Hypertension Unit, Mater Misericordiae University Hospital, Dublin, Ireland.
⁶ Pulmonary Hypertension Center, Institute of Cardiology, University of Bologna, Bologna, Italy.
⁷ Department of Clinical Cardiology, National Heart and Lung Institute, Imperial College London, London, United Kingdom.
⁸ Pulmonary and Critical Care Medicine, University of California San Diego School of Medicine, La Jolla, California.
⁹ Liu Center for Pulmonary Hypertension, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Torrance, California.
¹⁰ Department of Respiratory Medicine, Scottish Pulmonary Vascular Unit, University of Glasgow, Glasgow, Scotland, United Kingdom.
¹¹ Institute of Cardiology and Pulmonology, Laval University, Sainte-Foy, Québec, Canada.
¹² Centre des Maladies Vasculaires Pulmonaires, Hôpital Antoine Béclère, Clamart, France.
¹³ Division of Pulmonary and Critical Care Medicine, Duke University Medical Center, Durham, North Carolina.
¹⁴ Department of Internal Medicine, University of Giessen Lung Center, Giessen, Germany.

PMID: 19555863
DOI: 10.1016/j.jacc.2009.04.007

Abstract

New and emerging therapies might provide benefit in patients with pulmonary arterial hypertension. Their efficacy and safety will be compared with existing combination therapies in randomized clinical trials. Appropriate end points for these trials need to be identified: these will include exercise testing, the composite end point of time to clinical worsening, and hemodynamic markers, including advanced imaging modalities and biomarkers. Quality-of-life questionnaires are useful and important secondary end points; pulmonary arterial hypertension-specific questionnaires are currently being developed. Advantages and disadvantages of various trial designs, including placebo-controlled monotherapy or add-on trials, noninferiority studies, and withdrawal trials are also discussed.

Publication types

Review

MeSH terms

Clinical Trials as Topic*
Endpoint Determination*
Exercise Test
Hemodynamics
Humans
Hypertension, Pulmonary* / diagnosis
Hypertension, Pulmonary* / physiopathology
Hypertension, Pulmonary* / therapy
Quality of Life
Randomized Controlled Trials as Topic
Research Design
Respiratory Function Tests
Treatment Outcome