title: Feasibility of a clinical trial of augmentation therapy for alpha(1)-antitrypsin deficiency. The Alpha 1-Antitrypsin Deficiency Registry Study Group.
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.
authors.affiliation: Department of Biostatistics and Epidemiology, Cleveland Clinic Foundation, Cleveland, Ohio, USA.
authors.forename: M D
authors.initials: MD
authors.lastname: Schluchter
authors.forename: J K
authors.initials: JK
authors.lastname: Stoller
authors.forename: A F
authors.initials: AF
authors.lastname: Barker
authors.forename: A S
authors.initials: AS
authors.lastname: Buist
authors.forename: R G
authors.initials: RG
authors.lastname: Crystal
authors.forename: J F
authors.initials: JF
authors.lastname: Donohue
authors.forename: R J
authors.initials: RJ
authors.lastname: Fallat
authors.forename: G M
authors.initials: GM
authors.lastname: Turino
authors.forename: C E
authors.initials: CE
authors.lastname: Vreim
authors.forename: M C
authors.initials: MC
authors.lastname: Wu
mesh_terms: D000328:Adult; D005240:Feasibility Studies; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D008173:Lung Diseases, Obstructive / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D008297:Male; D016032:Randomized Controlled Trials as Topic; D012042:Registries; D015996:Survival Rate; D014481:United States; D000515:alpha 1-Antitrypsin / Q000008:administration & dosage*; D019896:alpha 1-Antitrypsin Deficiency / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality
chemical_list: D000515:alpha 1-Antitrypsin