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

Overview

MeSH

  • Adult
  • Feasibility Studies
  • Female
  • Forced Expiratory Volume
  • Humans
  • Infusions, Intravenous
  • Male
  • Registries
  • Survival Rate
  • United States

MeSH Major

  • 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.

publication date

  • March 2000

has subject area

  • Adult
  • Feasibility Studies
  • Female
  • Forced Expiratory Volume
  • Humans
  • Infusions, Intravenous
  • Lung Diseases, Obstructive
  • Male
  • Randomized Controlled Trials as Topic
  • Registries
  • Survival Rate
  • United States
  • alpha 1-Antitrypsin
  • alpha 1-Antitrypsin Deficiency

Research

keywords

  • Journal Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1164/ajrccm.161.3.9906011

PubMed ID

  • 10712324

Additional Document Info

start page

  • 796

end page

  • 801

volume

  • 161

number

  • 3 Pt 1