Feasibility of a clinical trial of augmentation therapy for α1- 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, Margaret C. Wu

Research output: Contribution to journalArticle

53 Scopus citations


We examined the feasibility of a randomized clinical trial of intravenous augmentation therapy for individuals with alpha 1-antitrypsin (α1AT) 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, α = 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.

Original languageEnglish (US)
Pages (from-to)796-801
Number of pages6
JournalAmerican journal of respiratory and critical care medicine
Issue number3 I
StatePublished - Jan 1 2000

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

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    Schluchter, M. D., Stoller, J. K., Barker, A. F., Buist, A. S., Crystal, R. G., Donohue, J. F., Fallat, R. J., Turino, G. M., Vreim, C. E., & Wu, M. C. (2000). Feasibility of a clinical trial of augmentation therapy for α1- antitrypsin deficiency. American journal of respiratory and critical care medicine, 161(3 I), 796-801. https://doi.org/10.1164/ajrccm.161.3.9906011