help button home button
AJRCCM
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
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 Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by SCHLUCHTER, M. D.
Right arrow Articles by WU, M. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by SCHLUCHTER, M. D.
Right arrow Articles by WU, M. C.

Am. J. Respir. Crit. Care Med., Volume 161, Number 3, March 2000, 796-801

Feasibility of a Clinical Trial of Augmentation Therapy for alpha 1-Antitrypsin Deficiency

MARK D. SCHLUCHTER, JAMES K. STOLLER, ALAN F. BARKER, A. SONIA BUIST, RONALD G. CRYSTAL, JAMES F. DONOHUE, ROBERT J. FALLAT, GERARD M. TURINO, CAROL E. VREIM, and MARGARET C. WU, for The Alpha 1-Antitrypsin Deficiency Registry Study Group

Department of Biostatistics and Epidemiology, Cleveland Clinic Foundation, Cleveland, Ohio; Department of Pulmonary and Critical Care Medicine, Cleveland Clinic Foundation, Cleveland, Ohio; Department of Pulmonary and Critical Care Medicine, Oregon Health Sciences University, Portland, Oregon; Division of Pulmonary and Critical Care Medicine, The New York Hospital/Cornell University, New York, New York; Pulmonary Division, Department of Medicine, University of North Carolina, Chapel Hill, North Carolina; Pulmonary Division, California Pacific Medical Center, San Francisco, California; Department of Medicine, Columbia University, New York, New York; and Division of Lung Diseases and Biostatistics Research Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland

We examined the feasibility of a randomized clinical trial of intravenous augmentation therapy for individuals with alpha 1-antitrypsin (alpha 1AT) deficiency, basing calculations on newly available data obtained from the NHLBI Registry of Patients with Severe Deficiency of Alpha 1-Antitrypsin. Using rate of FEV1 decline as the primary outcome and adjusting for noncompliance, a study of subjects with Stage II chronic obstructive pulmonary disease (COPD) (initial FEV1 35 to 49% predicted) with biannual spirometry measures obtained over 4 yr of follow-up would require 147 subjects per treatment arm to detect a difference in FEV1 decline of 23 ml/yr (i.e., a 28% reduction), the difference observed in the NHLBI Registry (1-sided test, alpha  = 0.05, 90% power). To detect a 40% reduction in mortality in a 5-year study of subjects with baseline FEV1 35 to 49% predicted, recruited over the first 2 yr and then followed an additional 3 yr, 342 subjects per treatment arm would be needed. Though significant impediments to carrying out a clinical trial exist, including the cost of such a trial and the potential difficulties in recruiting patients for a placebo-controlled trial, we recommend a randomized controlled trial as the best method to evaluate the efficacy of intravenous augmentation therapy and of possible future treatments. Schluchter MD, Stoller JK, Barker AF, Buist AS, Crystal RG, Donohue JF, Fallat RJ, Turino GM, Vreim CE, Wu MC, for the Alpha 1-Antitrypsin Deficiency Registry Study Group. Feasibility of a clinical trial of augmentation therapy for alpha 1-antitrypsin deficiency.




This article has been cited by other articles:


Home page
 Eur Respir JHome page
M. Cazzola, W. MacNee, F. J. Martinez, K. F. Rabe, L. G. Franciosi, P. J. Barnes, V. Brusasco, P. S. Burge, P. M. A. Calverley, B. R. Celli, et al.
Outcomes for COPD pharmacological trials: from lung function to biomarkers
Eur. Respir. J., February 1, 2008; 31(2): 416 - 469.
[Abstract] [Full Text] [PDF]

Home page
 Eur Respir JHome page
J.D. Newell Jr, J.C. Hogg, and G.L. Snider
Report of a workshop: quantitative computed tomography scanning in longitudinal studies of emphysema
Eur. Respir. J., May 1, 2004; 23(5): 769 - 775.
[Abstract] [Full Text] [PDF]

Home page
 Eur Respir JHome page
M. Luisetti, M. Miravitlles, and R.A. Stockley
{alpha}1-antitrypsin deficiency: a report from the 2nd meeting of the Alpha One International Registry, Rapallo (Genoa, Italy), 2001
Eur. Respir. J., October 1, 2002; 20(4): 1050 - 1056.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
M. J. TOBIN
Chronic Obstructive Pulmonary Disease, Pollution, Pulmonary Vascular Disease, Transplantation, Pleural Disease, and Lung Cancer in AJRCCM 2000
Am. J. Respir. Crit. Care Med., November 15, 2001; 164(10): 1789 - 1804.
[Full Text] [PDF]

Home page
 ChestHome page
M. Wencker, B. Fuhrmann, N. Banik, and N. Konietzko
Longitudinal Follow-up of Patients With {{alpha}}1-Protease Inhibitor Deficiency Before and During Therapy With IV {{alpha}}1-Protease Inhibitor
Chest, March 1, 2001; 119(3): 737 - 744.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
A. P. Fishman
One Hundred Years of Chronic Obstructive Pulmonary Disease
Am. J. Respir. Crit. Care Med., May 1, 2005; 171(9): 941 - 948.
[Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Proc. Am. Thorac. Soc. Am. J. Respir. Cell Mol. Biol.
Copyright © 2000 American Thoracic Society