Accurso 2010.
| Methods | 3‐arm RCT of parallel design. Multicentre: 13 centres reported. Duration: 28 days. |
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| Participants | Adults with CF with a G551D‐CFTR mutation on at least 1 allele. Total of 19 participants were enrolled in Part 2 of this trial. Gender n (%) Total cohort: 10 (53) males; Treatment group 1: 3 (38) males; Treatment group 2: 4 (57) males; Control group: 3 (75) males. White race n (%) Total cohort: 19 (100); Treatment group 1: 8 (100); Treatment group 2: 7 (100); Control group: 4 (100). Age median (range) Total cohort: 21 (18 ‐ 42) years; Treatment group 1: 23 (18 ‐ 40) years; Treatment group 2: 21 (20 ‐ 38) years; Control group: 24 (18 ‐ 42) years. BMI median (range) Total cohort: 22 (20 ‐ 25); Treatment group 1: 22 (20 ‐ 23); Treatment group 2: 23 (20 ‐ 25); Control group: 22 (21 ‐ 23). CFTR Genotype n (%) G551D/F508del Total cohort: 16 (84); Treatment group 1: 7 (88); Treatment group 2: 5 (71); Control group: 4 (100). G551D/3849+10kbC→T Total cohort: 1 (5); Treatment group 1: 0 (0); Treatment group 2: 1 (14) Control group: 0 (0). G551D/621+1G→T Total cohort: 1 (5); Treatment group 1: 1 (12); Treatment group 2: 0 (0); Control group: 0 (0). G551D/G542X Total cohort: 1 (5); Treatment group 1: 0 (0); Treatment group 2: 1 (14); Control group: 0 (0). FEV1 % predicted Median (range) Total cohort: 69 (40 ‐ 122); Treatment group 1: 65 (42 ‐ 122); Treatment group 2: 76 (40 ‐ 106); Control group: 77 (53 ‐ 112). 40% to <70% n (%) Total cohort: 10 (53); Treatment group 1: 5 (62); Treatment group 2: 3 (43); Control group: 2 (50). 70% to <90% n (%) Total cohort: 5 (26); Treatment group 1: 2 (25); Treatment group 2: 3 (43); Control group: 0 (0). ≥90% value n (%) Total cohort: 4 (21); Treatment group 1: 1 (12); Treatment group 2: 1 (14); Control group: 2 (50). Sweat chloride (mmol/L) mean (range) Total cohort: 95.5 (84.8 ‐ 115.8); Treatment group 1: 100.1 (86.8 ‐ 112.5); Treatment group 2: 97.3 (84.8 ‐ 115.8); Control group: 93.8 (88.0 ‐ 109.5). CFQ‐R respiratory domain (points) mean (range) Total cohort: 72.2 (16.7 ‐ 88.9); Treatment group 1: 69.4 (16.7 ‐ 88.9); Treatment group 2: 72.2 (61.1 ‐ 83.3); Control group: 80.6 (38.9 ‐ 83.3). |
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| Interventions | Treatment Group 1: VX‐770 150 mg 2x daily (n = 8). Treatment Group 2; VX‐770 250 mg 2x daily (n = 7). Control: placebo 2x daily (n = 4). |
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| Outcomes |
Primary outcome: 1. Safety and adverse effects* Secondary outcomes: 1. CFTR ion channel function. 2. Change in QoL from baseline* 3. Relative change from baseline in FEV1* 4. Relative change from baseline in FVC* and relative change from baseline in FEF25‐75 5. Change from baseline in sweat chloride concentration.* |
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| Notes | This was a 2‐part trial; part 1 was of cross‐over design and so not included in this review. We only present details of the second part which was of parallel design. The responsible funding body was Vertex Pharmaceuticals Incorporated. * These outcomes are presented in the review. |
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| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Randomisation list generated by a statistician not otherwise associated with the trial. |
| Allocation concealment (selection bias) | Low risk | Participants assigned to a treatment arm using an Interactive Voice Response system according to a concealed randomisation list. This ensured the outcome assessors and participants were unaware of their allocation. |
| Blinding (performance bias and detection bias) All outcomes | Low risk | All trial personnel were blinded to participants' treatment. Exceptions to this were the laboratory staff and clinical pharmacist who prepared the medication. These trial personnel were not otherwise involved in the trial. |
| Blinding of participants | Unclear risk | All participants received the same number of tablets to maintain trial and personnel blinding. However, there is no report on details of the tablets (e.g. colour, size, taste). |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | All together, 20 participants were randomised. 1 of 5 placebo participants withdrew due to withdrawal of consent prior to dosing (5% of total participants). All other participants were accounted for in the analysis. |
| Selective reporting (reporting bias) | High risk | The change from baseline in weight, although not reported as an outcome, was measured at day 1, 3, 14, 21 and 28. It was not reported in the publication. |
| Other bias | Low risk | Similar baseline characteristics and high adherence rate (100% [range, 92.6 ‐ 100]). |