Introduction: Alpha 1 -Antitrypsin Deficiency (AATD) is a hereditary condition characterized by low serum levels of alpha 1 -proteinase inhibitor (alpha 1 -PI) and an increased risk of emphysema. The approved dose for augmentation therapy is 60 mg/kg/wk, associated with raising trough levels to approximately 11 µM. However, the normal lower limit in the nondeficient population is 20 µM. To date, no prospective randomized controlled trial has conclusively proven the clinical efficacy of augmentation therapy. Goal: To assess the effect of augmentation therapy on emphysema progression in AATD assessed by lung computed tomography (CT) densitometry, dosed to approximate trough levels of 11 µM or 20 µM, vs placebo. SPARTA will be the largest randomized trial with the longest duration of exposure, and the first to compare two active augmentation arms. Design: Prospective, double-blind, randomized, placebo-controlled Arms 60 mg/kg/wk vs 120 mg/kg/wk of intravenous alpha 1 -PI, vs placebo Duration 3 years Primary Endpoint Lung loss via whole lung CT densitometry (15th percentile point) in each active arm vs placebo Other Endpoints - Severe COPD exacerbations - Basal lung CT densitometry - Forced expiratory volume in 1 sec - Quality of life Sample Size Total of 339 subjects (80% power at 0.025 level with an assumed 20% dropout) Discussion: SPARTA will be the first prospective, randomized controlled trial of augmentation to assess two active doses, including one designed to achieve population based normal trough levels, vs placebo.Enrollment is anticipated to commence in September 2013 and should allow analyses of a number of secondary endpoints and subject subpopulations.
Forshag et al. (Sun,) studied this question.
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