Table 6 Published randomised controlled trials Trial ID Eligibility criteria of patients Product Dosing strategy Comparator Follow up Outcomes (FEV1, genetic variant or serum Level of evidence A1-PI levels if given) Published trials Dirksen et al. α1-antitrypsin deficiency of Prolastin-C 250 mg/kg body Placebo: albumin 625 36 months Pulmonary function testing: FEV1, carbon (1999) PI*ZZ phenotype from weight mg/kg body weight monoxide diffusion constant (Kco), diffusion isoelectric focusing; moderate capacity (Dl CO) at 3mo intervals; patient RCT Every 4 weeks to severe emphysema (FEV1 administered serial spirometry daily; CT between 30% and 80% of annually predicted); ceased smoking since 6 months EXACTLE Severe congenital α1-AT Prolastin® 60 mg/kg body Placebo: 2% albumin 24 months Pulmonary function testing: FEV1, diffusing (Dirksen et al. deficiency (with α1-AT serum weight capacity of the lung for carbon monoxide 2009) concentration <11 μM) ; ceased weekly (DL,CO), transfer coefficient of the lung for smoking since 6 months carbon monoxide (KCO); frequency of RCT exacerbations collected in diary RAPID M/F aged 18‒65 with Zemaira 60 mg/kg body Placebo 24 months Primary: Lung density CT at 3, 12, 21 and (Chapman et al. emphysema secondary to α1 weight 24 months; 15th percentile CT lung density 2015; McElvaney antitrypsin deficiency (serum weekly at functional residual capacity and total lung et al. 2017) A1PI concentration of ≤11 μM) capacity. and FEV1, 0f 35‒70% of RCT Secondary: Number of exacerbations; FEV1; predicted; ceased smoking single-breath diffusion capacity; baseline; since 6 months A1PI concentrations (functional and antigenic assays); incremental shuttle walk; health status; body-mass index; mortality; and safety.
Table 6 Published randomised controlled trials Trial ID Level of evidence Eligibility criteria of patients (FEV1, genetic variant or serum A1-PI levels if given) Product Dosing strategy Comparator Follow up Outcomes Published trials Dirksen et al. (1999) RCT α1-antitrypsin deficiency of PI*ZZ phenotype from isoelectric focusing; moderate to severe emphysema (FEV1 between 30% and 80% of predicted); ceased smoking since 6 months Prolastin-C 250 mg/kg body weight Every 4 weeks Placebo: albumin 625 mg/kg body weight 36 months Pulmonary function testing: FEV1, carbon monoxide diffusion constant (Kco), diffusion capacity (Dl CO) at 3mo intervals; patient administered serial spirometry daily; CT annually EXACTLE (Dirksen et al. 2009) RCT Severe congenital α1-AT deficiency (with α1-AT serum concentration <11 μM) ; ceased smoking since 6 months Prolastin® 60 mg/kg body weight weekly Placebo: 2% albumin 24 months Pulmonary function testing: FEV1, diffusing capacity of the lung for carbon monoxide (DL,CO), transfer coefficient of the lung for carbon monoxide (KCO); frequency of exacerbations collected in diary RAPID (Chapman et al. 2015; McElvaney et al. 2017) RCT M/F aged 18‒65 with emphysema secondary to α1 antitrypsin deficiency (serum A1PI concentration of ≤11 μM) and FEV1, 0f 35‒70% of predicted; ceased smoking since 6 months Zemaira 60 mg/kg body weight weekly Placebo 24 months Primary: Lung density CT at 3, 12, 21 and 24 months; 15th percentile CT lung density at functional residual capacity and total lung capacity. Secondary: Number of exacerbations; FEV1; single-breath diffusion capacity; baseline; A1PI concentrations (functional and antigenic assays); incremental shuttle walk; health status; body-mass index; mortality; and safety.