Traditional and alternative designs for pulmonary arterial hypertension trials

Proceedings of the American Thoracic Society

Volumn 5, Issue 5, 2008, Pages 610-616

  Gomberg Maitland, Mardi ^a  

^a UNIVERSITY OF CHICAGO MEDICAL CENTER   (United States)

Author keywords

Clinical trials; Drug development; Pulmonary hypertension

Indexed keywords

AMINO TERMINAL PRO BRAIN NATRIURETIC PEPTIDE; BRAIN NATRIURETIC PEPTIDE; PLACEBO; PROSTACYCLIN; UNIPROST;

ASCITES; CLINICAL TRIAL; COLLAPSE; CONFERENCE PAPER; DRUG APPROVAL; DRUG DOSE TITRATION; DRUG EFFICACY; DRUG RESEARCH; DRUG SAFETY; DRUG TOLERABILITY; FACTORIAL DESIGN; HUMAN; LUNG EDEMA; MAXIMUM TOLERATED DOSE; METHODOLOGY; MONOTHERAPY; PULMONARY HYPERTENSION; QUALITY OF LIFE; RISK BENEFIT ANALYSIS; TREADMILL EXERCISE; TREATMENT INDICATION;

ANTIHYPERTENSIVE AGENTS; CLINICAL TRIALS AS TOPIC; HUMANS; HYPERTENSION, PULMONARY; REPRODUCIBILITY OF RESULTS;

EID: 47749138181     PISSN: 15463222     EISSN: None     Source Type: Journal    
DOI: 10.1513/pats.200803-024SK     Document Type: Conference Paper

References (48)

1. D'Alonzo G, Barst R, Ayres S, Stephen M, Bergofsky EHB, Bruce H. Detre KM, Fishman AP, Goldring RM, Groves BM, et al. Survival in patients with primary pulmonary hypertension: results from a national prospective registry. Ann Intern Med 1991;115:343-349.
2. Rich S, Dantzker R, Ayres S, Bergofsky E, Brundage B, Detre K, Fishman A, Goldring R, Groves B, Koerner S, et al. Primary pulmonary hypertension: a national prospective study. Ann Intern Med 1987;107:216-223.
3. Barst R, Rubin L, Long W, McGoon M, Rich S, Badesch D, Groves B, Tapson V, Bourge R, Brundage B, et al. A comparison of continuous intravenous epoprostenol (prostacyclin) with conventional therapy for primary pulmonary hypertension. N Engl J Med 1996;334:296-301.
4. Olschewski H, Simonneau G, Galie N, Higenbottam T, Naeije R, Rubin L, Nikkho S, Speich R, Hoeper M, Behr J, et al. Inhaled iloprost for severe pulmonary hypertension. N Engl J Med 2002;347:322-329.
5. Rubin L, Roux S. Bosentan: a dual endothelin receptor antagonist. Expert Opinion Investig Drugs 2002;11:991-1002.
6. Simonneau G, Barst RJ, Galie N, Naeije R, Rich S, Bourge RC, Keogh A, Oudiz R, Frost A, Blackburn SD, et al. Continuous subcutaneous infusion of treprostinil, a prostacyclin analogue, in patients with pulmonary arterial hypertension: a double-blind, randomized, placebo-controlled trial. Am J Respir Crit Care Med 2002;165:800-804.
7. McLaughlin VV, Shillington A, Rich S. Survival in primary pulmonary hypertension: the impact of epoprostenol therapy. Circulation 2002;106:1477-1482.
8. Sitbon O, Humbert M, Nunes H, Parent F, Garcia G, Herve P, Rainisio M, Simonneau G. Long-term intravenous epoprostenol infusion in primary pulmonary hypertension: prognostic factors and survival. J Am Coll Cardiol 2002;40:780-788.
9. Galie N, Badesch D, Oudiz R, Simonneau G, McGoon MD, Keogh AM, Frost AE, Zwicke D, Naeije R, Shapiro S, et al. Ambrisentan therapy for pulmonary arterial hypertension. J Am Coll Cardiol 2005;46:529-535.
10. Galie N, Ghofrani HA, Torbicki A, Barst RJ, Rubin LJ, Badesch D, Fleming T, Parpia T, Burgess G, Branzi A, et al. Sildenafil citrate therapy for pulmonary arterial hypertension. N Engl J Med 2005;353:2148-2157.
11. Gomberg-Maitland M, Tapson VF, Benza RL, McLaughlin VV, Krichman A, Widlitz AC, Barst RJ. Transition from intravenous epoprostenol to intravenous treprostinil in pulmonary hypertension. Am J Respir Crit Care Med 2005;172:1586-1589.
12. Tapson VF, Gomberg-Maitland M, McLaughlin VV, Benza RL, Widlitz AC, Krichman A, Barst RJ. Safety and efficacy of IV treprostinil for pulmonary arterial hypertension: a prospective, multicenter, open-label, 12-week trial. Chest 2006;129:683-688.
13. Barst RJ, Galie N, Naeije R, Simonneau G, Jeffs R, Arneson C, Rubin LJ. Long-term outcome in pulmonary arterial hypertension patients treated with treprostinil. Eur Respir J 2006;28:195-203.
14. Humbert M, Sitbon O, Chaouat A, Bertocchi M, Habib G, Gressin V, Yaici A, Weitzenblum E, Cordier JF, Chabot F, et al. Pulmonary arterial hypertension in France: results from a national registry. Am J Respir Crit Care Med 2006;173:1023-1030.
15. Thenappan T, Shah SJ, Rich S, Gomberg-Maitland M. A USA-based registry for pulmonary arterial hypertension: 1982-2006. Eur Respir J 2007;30:1103-1110.
16. Gomberg-Maitland M. Learning to pair therapies and the expanding matrix for pulmonary arterial hypertension: is more better? Eur Respir J 2006;28:683-686.
17. Macchia A, Marchioli R, Marfisi R, Scarano M, Levantesi G, Tavazzi L, Tognoni G. A meta-analysis of trials of pulmonary hypertension: a clinical condition looking for drugs and research methodology. Am Heart J 2007;153:1037-1047.
18. Gomberg-Maitland M, Thenappan T, Rizvi K, Chandra S, Meads DM, McKenna SP. United States validation of the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR). J Heart Lung Transplant 2008;27:124-130.
19. McKenna SP, Doughty N, Meads DM, Doward LC, Pepke-Zaba J. The Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR): a measure of health-related quality of life and quality of life for patients with pulmonary hypertension. Qual Life Res 2006;15:103-115.
20. Ulett KB, Marwick TH. Incorporation of pulmonary vascular resistance measurement into standard echocardiography: implications for assessment of pulmonary hypertension. Echocardiography 2007;24:1020-1022.
21. Jenkins C, Chan J, Bricknell K, Strudwick M, Marwick TH. Reproducibility of right ventricular volumes and ejection fraction using real-time three-dimensional echocardiography: comparison with cardiac MRI. Chest 2007;131:1844-1851.
22. Palevsky H, Schloo B, Pietra G, Weber K, Janicki J, Rubin E, Fishman A. Primary pulmonary hypertension: vascular structure, morphometry, and responsiveness to vasodilator agents. Circulation 1989;80:1207-1221.
23. Halpern SD, Karlawish JH, Berlin JA. The continuing unethical conduct of underpowered clinical trials. JAMA 2002;288:358-362.
24. Temple RJ. When are clinical trials of a given agent vs. placebo no longer appropriate or feasible? Control Clin Trials 1997;18:613-620. [Discussion, pp. 661-616.]
25. Ellenberg SS, Temple R. Placebo-controlled trials and active-control trials in the evaluation of new treatments. Part 2: practical issues and specific cases. Ann Intern Med 2000;133:464-470.
26. Rothman KJ, Michels KB. The continuing unethical use of placebo controls. N Engl J Med 1994;331:394-398.
27. Helman DL Jr, Brown AW, Jackson JL, Shorr AF. Analyzing the short-term effect of placebo therapy in pulmonary arterial hypertension: potential implications for the design of future clinical trials. Chest 2007;132:764-772.
28. Sheiner LB. Learning versus confirming in clinical drug development. Clin Pharmacol Ther 1997;61:275-291.
29. Hyman AL, Kadowitz PJ. Pulmonary vasodilator activity of prostacyclin (PGI2) in the cat. Circ Res 1979;45:404-409.
30. Leffler CW, Hessler JR. Pulmonary and systemic vascular effects of exogenous prostaglandin I2 in fetal lambs. Eur J Pharmacol 1979;54:37-42.
31. Starling MB, Neutze JM, Elliott RL. Control of elevated pulmonary vascular resistance in neonatal swine with prostacyclin (PGI2). Prostaglandins Med 1979;3:105-117.
32. Watkins WD, Peterson MB, Crone RK, Shannon DC, Levine L. Prostacyclin and prostaglandin E1 for severe idiopathic pulmonary artery hypertension. Lancet 1980;1:1083.
33. Data JL, Molony BA, Meinzinger MM, Gorman RR. Intravenous infusion of prostacyclin sodium in man: clinical effects and influence on platelet adenosine diphosphate sensitivity and adenosine 3′,5′-cyclic monophosphate levels. Circulation 1981;64:4-12.
34. Rubin LJ, Groves BM, Reeves JT, Frosolono M, Handel F, Cato AE. Prostacyclin-induced acute pulmonary vasodilation in primary pulmonary hypertension. Circulation 1982;66:334-338.
35. Gomberg-Maitland M, Huo D, Benza RL, McLaughlin VV, Tapson VF, Barst RJ. Creation of a model comparing 6-minute walk test to metabolic equivalent in evaluating treatment effects in pulmonary arterial hypertension. J Heart Lung Transplant 2007;26:732-738.
36. Ratain MJ. Phase II oncology trials: let's be positive. Clin Cancer Res 2005;11:5661-5662.
37. Kopec JA, Abrahamowicz M, Esdaile JM. Randomized discontinuation trials: utility and efficiency. J Clin Epidemiol 1993;46:959-971.
38. Ratain MJ, Eisen T, Stadler WM, Flaherty KT, Kaye SB, Rosner GL, Gore M, Desai AA, Patnaik A, Xiong HQ, et al. Phase II placebo-controlled randomized discontinuation trial of sorafenib in patients with metastatic renal cell carcinoma. J Clin Oncol 2006;24:2505-2512.
39. Rubin L, Mendoza J, Hood M, McGoon M, Barst R, Williams W, Diehl J, Crow J, Long W. Treatment of primary pulmonary hypertension with continuous intravenous prostacyclin (epoprostenol). Ann Intern Med 1990;112:485-491.
40. Barst R, Rubin L, McGoon M, Caldwell E, Long W, Levey P. Survival in primary pulmonary hypertension with long-term continuous intravenous prostacyclin. Ann Intern Med 1994;121:409-415.
41. Gomberg-Maitland M, Frison L, Halperin JL. Active-control clinical trials to establish equivalence or noninferiority: methodological and statistical concepts linked to quality. Am Heart J 2003;146:398-403.
42. Rubenfire M, McLaughlin VV, Allen RP, Elliott G, Park MH, Wade M, Schilz R. Transition from IV epoprostenol to subcutaneous treprostinil in pulmonary arterial hypertension: a controlled trial. Chest 2007;132:757-763.
43. Jones B, Jarvis P, Lewis JA, Ebbutt AF. Trials to assess equivalence: the importance of rigorous methods. BMJ 1996;313:36-39.
44. Siegel JP. Equivalence and noninferiority trials. Am Heart J 2000;139: S166-S170.
45. Fleming TR. Design and interpretation of equivalence trials. Am Heart J 2000;139:S171-S176.
46. Lubsen J, Pocock SJ. Factorial trials in cardiology: pros and cons. Eur Heart J 1994;15:585-588.
47. Robbins IM, Kawut SM, Yung D, Reilly MP, Lloyd W, Cunningham G, Loscalzo J, Kimmel SE, Christman BW, Barst RJ. A study of aspirin and clopidogrel in idiopathic pulmonary arterial hypertension. Eur Respir J 2006;27:578-584.
48. Halpern SD, Doyle R, Kawut SM. The ethics of randomized clinical trials in pulmonary arterial hypertension. Proc Am Thorac Soc 2008;5:631-636.