Feasibility of a clinical trial of augmentation therapy for alpha(1)-antitrypsin deficiency. The Alpha 1-Antitrypsin Deficiency Registry Study Group.

Publication Type	Academic Article
Authors	Schluchter M, Stoller J, Barker A, Buist A, Crystal R, Donohue J, Fallat R, Turino G, Vreim C, Wu M
Journal	Am J Respir Crit Care Med
Volume	161
Issue	3 Pt 1
Pagination	796-801
Date Published	03/01/2000
ISSN	1073-449X
Keywords	Lung Diseases, Obstructive, Randomized Controlled Trials as Topic, alpha 1-Antitrypsin, alpha 1-Antitrypsin Deficiency
Abstract	We examined the feasibility of a randomized clinical trial of intravenous augmentation therapy for individuals with alpha 1-antitrypsin (alpha1AT) deficiency, basing calculations on newly available data obtained from the NHLBI Registry of Patients with Severe Deficiency of Alpha 1-Antitrypsin. Using rate of FEV(1) decline as the primary outcome and adjusting for noncompliance, a study of subjects with Stage II chronic obstructive pulmonary disease (COPD) (initial FEV(1) 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 FEV(1) 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 FEV(1) 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.
DOI	10.1164/ajrccm.161.3.9906011
PubMed ID	10712324