Table 2 Summary of clinical studies investigating the efficacy of ivacaftor in patients with cystic fibrosis and the Gly551Asp mutation
From: Targeted therapies to improve CFTR function in cystic fibrosis
Study name and reference | Accurso et al. 2010 [42] | STRIVE: Ramsey et al. 2011 [6] | ENVISION: Davies et al. 2013 [43] | Davies et al. 2013 [44] | Barry et al. 2014 [45] | |
|---|---|---|---|---|---|---|
Type of study | Phase II RCT | Phase III RCT | Phase III RCT | Phase III RCT | Case–control study | |
Number of participants | n = 39 | n = 161 | n = 52 | n = 21 | n = 56 | |
Ivacaftor: 31; placebo: 8 | Ivacaftor: 83; placebo: 78 | Ivacaftor: 26; placebo: 22 | Â | Ivacaftor: 21; placebo: 35 | ||
Duration | 28Â days | 48Â weeks | 48Â weeks | 29Â days | 9Â months | |
Inclusion criteria | ≥18 years | ≥12 years | 6–11 years | ≥6 years | ≥18 years | |
≥1 Gly551Asp allele | ≥1 Gly551Asp allele | ≥1 Gly551AspP allele | ≥1 Gly551Asp allele | ≥1 Gly551Asp allele | ||
FEV1 > 40 % | FEV1 40–90 % | FEV1 40–105 % | FEV1 > 90 % | FEV1 < 40 % | ||
Weight ≥15 kg | LCI >7.4 | and/or actively listed for lung transplant | ||||
Weight ≥15 kg | ||||||
Outcome measure | Median change from baseline with 150Â mg | Treatment effect | Treatment effect | Treatment effect | Changes within treated patients | Treated patients versus controls |
Mean FEV1 (percentage predicted) | +8.7 (P = 0.008) | 24 weeks: +10.6 (P < 0.001) | 24 weeks: +12.5 (P < 0.001) | – | +4.2 (P = 0.0068) | +3.8 versus 0.6 (P = 0.009; median) |
48 weeks: +10.5 (P < 0.001) | 48 weeks: +10 (P < 0.0006) | |||||
Sweat chloride levels (mmol/L) | −59.5 (P = 0.008) | −47.9 (P < 0.001) | −54.3 (P < 0.001) | – | – | – |
CFQ-R score (points) | +8.3 (P = 0.06) | +8.6 (P < 0.001) | +6.1 (P = 0.109) | – | – | – |
Nasal potential difference (mV) | −3.5 (P = 0.02) | – | – | – | – | – |
Weight (kg) | – | +2.7 (P < 0.001) | +2.8 (P < 0.001) | – | +1.8 (P = 0.0058; median) | +2.3 versus 0.6 (P = 0.25; median) |
BMI | – | – | BMI-for-age z-score: 0.45 (P < 0.001) | – | +1.1 kg/m2 (P = 0.010; median) | +0.84 versus 0.2 kg/m2 (P = 0.234; median) |
Time on intravenous antibiotics (days per year) | – | – | – | – | −36 (P = 0.0016; median) | −36 versus +10 (P = 0.0003; median) |
Pulmonary exacerbations | – | 55 % risk reduction | No significant difference | – | – | – |
(0.455 hazard ratio: P = 0.001) | ||||||
LCI | – | – | – | −2.16 (P < 0.0001) | – | – |