Feasibility of a clinical trial of augmentation therapy for alpha(1)-antitrypsin deficiency. The Alpha 1-Antitrypsin Deficiency Registry Study Group.
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.
Schluchter
M D
MD
Department of Biostatistics and Epidemiology, Cleveland Clinic Foundation, Cleveland, Ohio, USA.
Stoller
J K
JK
Barker
A F
AF
Buist
A S
AS
Crystal
R G
RG
Donohue
J F
JF
Fallat
R J
RJ
Turino
G M
GM
Vreim
C E
CE
Wu
M C
MC
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
D000515:alpha 1-Antitrypsin