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

Am J Respir Crit Care Med. 2000 Mar;161(3 Pt 1):796-801. doi: 10.1164/ajrccm.161.3.9906011.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Feasibility Studies
  • Female
  • Forced Expiratory Volume / drug effects
  • Humans
  • Infusions, Intravenous
  • Lung Diseases, Obstructive / drug therapy*
  • Lung Diseases, Obstructive / genetics
  • Lung Diseases, Obstructive / mortality
  • Male
  • Randomized Controlled Trials as Topic*
  • Registries
  • Survival Rate
  • United States
  • alpha 1-Antitrypsin / administration & dosage*
  • alpha 1-Antitrypsin Deficiency / drug therapy*
  • alpha 1-Antitrypsin Deficiency / genetics
  • alpha 1-Antitrypsin Deficiency / mortality


  • alpha 1-Antitrypsin