JACC
HOME SUBSCRIPTIONS CURRENT ISSUE PAST ISSUES CARDIOSOURCE SEARCH HELP FEEDBACK
 QUICK SEARCH:   [advanced]


     


J Am Coll Cardiol, 2004; 43:48-55
© 2004 by the American College of Cardiology Foundation
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Hoeper, M. M.
Right arrow Articles by Torbicki, A.
Right arrow Search for Related Content
PubMed
Right arrow Articles by Hoeper, M. M.
Right arrow Articles by Torbicki, A.

End points and clinical trial designs in pulmonary arterial hypertension

Clinical and regulatory perspectives

Marius M. Hoeper, MD*,*, Ronald J. Oudiz, MD{dagger}, Andrew Peacock, MD{ddagger}, Victor F. Tapson, MD§, Sheila G. Haworth, MD||, Adaani E. Frost, MD and Adam Torbicki, MD

* Department of Respiratory Medicine, Hannover Medical School, Hannover, Germany
{dagger} Division of Cardiology, Harbor—UCLA Medical Center, Torrance, California, USA
{ddagger} Scottish Pulmonary Vascular Unit, Glasgow, Scotland, UK
§ Pulmonary Hypertension Center, Duke University Medical Center, Durham, North Carolina, USA
|| Institute of Child Health, London, United Kingdom
Baylor College of Medicine, Houston, Texas, USA
Institute of Tuberculosis and Lung Diseases, University of Warsaw, Warsaw, Poland

Manuscript received November 26, 2003; accepted February 3, 2004.

* Reprint requests and correspondence: Dr. Marius M. Hoeper, Department of Respiratory Medicine, Hannover Medical School, 30623 Hannover, Germany.
hoeper.marius{at}mh-hannover.de

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.

Abbreviations and Acronyms
  BNP = brain natriuretic peptide
  CO = cardiac output
  CPET = cardiopulmonary exercise testing
  EMEA = European Agency for the Evaluation of Medicinal Products
  FDA = Food and Drug Administration
  LV = left ventricle/ventricular
  NYHA = New York Heart Association
  PAH = pulmonary arterial hypertension
  PAP = pulmonary artery pressure
  PAPm = mean pulmonary artery pressure
  PCWP = pulmonary capillary wedge pressure
  PVR = pulmonary vascular resistance
  QoL = quality of life
  RV = right ventricle/ventricular
  VO 2 = oxygen consumption
  WHO = World Health Organization




This article has been cited by other articles:


Home page
Eur Heart JHome page
B. G. Stevinson, J. Hernandez-Nino, G. Rose, and J. A. Kline
Echocardiographic and functional cardiopulmonary problems 6 months after first-time pulmonary embolism in previously healthy patients
Eur. Heart J., October 2, 2007; 28(20): 2517 - 2524.
[Abstract] [Full Text] [PDF]


Home page
ChestHome page
D. L. Helman Jr, A. W. Brown, J. L. Jackson, and A. F. Shorr
Analyzing the Short-term Effect of Placebo Therapy in Pulmonary Arterial Hypertension: Potential Implications for the Design of Future Clinical Trials
Chest, September 1, 2007; 132(3): 764 - 772.
[Abstract] [Full Text] [PDF]


Home page
CirculationHome page
G.-P. Diller and M. A. Gatzoulis
Pulmonary Vascular Disease in Adults With Congenital Heart Disease
Circulation, February 27, 2007; 115(8): 1039 - 1050.
[Abstract] [Full Text] [PDF]


Home page
J Am Coll CardiolHome page
M. M. Hoeper, S. H. Lee, R. Voswinckel, M. Palazzini, X. Jais, A. Marinelli, R. J. Barst, H. A. Ghofrani, Z.-C. Jing, C. Opitz, et al.
Complications of Right Heart Catheterization Procedures in Patients With Pulmonary Hypertension in Experienced Centers
J. Am. Coll. Cardiol., December 19, 2006; 48(12): 2546 - 2552.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Respir. Crit. Care Med.Home page
V. V. McLaughlin, R. J. Oudiz, A. Frost, V. F. Tapson, S. Murali, R. N. Channick, D. B. Badesch, R. J. Barst, H. H. Hsu, and L. J. Rubin
Randomized Study of Adding Inhaled Iloprost to Existing Bosentan in Pulmonary Arterial Hypertension
Am. J. Respir. Crit. Care Med., December 1, 2006; 174(11): 1257 - 1263.
[Abstract] [Full Text] [PDF]


Home page
Rheumatology (Oxford)Home page
O. Distler, F. Behrens, D. Huscher, I. Foeldvari, A. Zink, P. Nash, C. P. Denton, M. Humbert, M. Matucci-Cerinic, J. Seibold, et al.
Need for improved outcome measures in pulmonary arterial hypertension related to systemic sclerosis
Rheumatology, December 1, 2006; 45(12): 1455 - 1457.
[Full Text] [PDF]


Home page
Eur Respir JHome page
E. Cenedese, R. Speich, L. Dorschner, S. Ulrich, M. Maggiorini, R. Jenni, and M. Fischler
Measurement of quality of life in pulmonary hypertension and its significance
Eur. Respir. J., October 1, 2006; 28(4): 808 - 815.
[Abstract] [Full Text] [PDF]


Home page
Proc Am Thorac SocHome page
A. Peacock, G. Simonneau, and L. Rubin
Controversies, Uncertainties and Future Research on the Treatment of Chronic Thromboembolic Pulmonary Hypertension
Proceedings of the ATS, September 1, 2006; 3(7): 608 - 614.
[Abstract] [Full Text] [PDF]


Home page
ChestHome page
D. Bonderman, R. Nowotny, N. Skoro-Sajer, J. Jakowitsch, C. Adlbrecht, W. Klepetko, and I. M. Lang
Bosentan Therapy for Inoperable Chronic Thromboembolic Pulmonary Hypertension
Chest, October 1, 2005; 128(4): 2599 - 2603.
[Abstract] [Full Text] [PDF]


Home page
ANN INTERN MEDHome page
L. J. Rubin and D. B. Badesch
Evaluation and Management of the Patient with Pulmonary Arterial Hypertension
Ann Intern Med, August 16, 2005; 143(4): 282 - 292.
[Abstract] [Full Text] [PDF]




HOME SUBSCRIPTIONS CURRENT ISSUE PAST ISSUES CARDIOSOURCE SEARCH HELP FEEDBACK
Copyright © 2004 by the American College of Cardiology Foundation.