Trial reportThe Lancet. Respiratory medicine2015
Efficacy and safety of ivacaftor in patients with cystic fibrosis who have an Arg117His-CFTR mutation: a double-blind, randomised controlled trial.
Trial report in The Lancet. Respiratory medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 98 papers, 6 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of Ivacaftor in Subjects With Cystic Fibrosis Who Have the R117H-CFTR Mutation
A Phase 3, Two-Arm, Rollover Study to Evaluate the Safety of Long Term Ivacaftor Treatment in Subjects 6 Years of Age and Older With Cystic Fibrosis and a Non-G551D CFTR Mutation
Who cites it
98 citing papers in PubMed, 6 syntheses or guidelines pooled it, 224 citations in OpenAlex.
- Ivacaftor-tezacaftor-elexacaftor, tezacaftor-ivacaftor and lumacaftor-ivacaftor for treating cystic fibrosis: a systematic review and economic evaluation.Health technology assessment (Winchester, England) · 2025Pooled it
- Brazilian guidelines for the pharmacological treatment of the pulmonary symptoms of cystic fibrosis. Official document of the Sociedade Brasileira de Pneumologia e Tisiologia (SBPT, Brazilian Thoracic Association).Jornal brasileiro de pneumologia : publicacao oficial da Sociedade Brasileira de Pneumologia e Tisilogia · 2023Guideline
- Academy of Nutrition and Dietetics: 2020 Cystic Fibrosis Evidence Analysis Center Evidence-Based Nutrition Practice Guideline.Journal of the Academy of Nutrition and Dietetics · 2021Guideline
- From Ivacaftor to Triple Combination: A Systematic Review of Efficacy and Safety of CFTR Modulators in People with Cystic Fibrosis.International journal of molecular sciences · 2020Pooled it
- A Systematic Review of the Clinical Efficacy and Safety of CFTR Modulators in Cystic Fibrosis.Scientific reports · 2019Pooled it
- Potentiators (specific therapies for class III and IV mutations) for cystic fibrosis.The Cochrane database of systematic reviews · 2019Pooled it
- Trial
- Ivacaftor in Infants Aged 4 to <12 Months with Cystic Fibrosis and a Gating Mutation. Results of a Two-Part Phase 3 Clinical Trial.American journal of respiratory and critical care medicine · 2021Trial
- G970R-CFTR Mutation (c.2908G>C) Results Predominantly in a Splicing Defect.Clinical and translational science · 2021Trial
- Tezacaftor/Ivacaftor in Subjects with Cystic Fibrosis and F508del/F508del-CFTR or F508del/G551D-CFTR.American journal of respiratory and critical care medicine · 2018Trial
- Tezacaftor-Ivacaftor in Residual-Function Heterozygotes with Cystic Fibrosis.The New England journal of medicine · 2017Trial
- In vivo and in vitro ivacaftor response in cystic fibrosis patients with residual CFTR function: N-of-1 studies.Pediatric pulmonology · 2017Trial
- Pilot evaluation of ivacaftor for chronic bronchitis.The Lancet. Respiratory medicine · 2016Trial
- A DNA Tetrahedron-Delivered miR-17-5p mimic exerts dual anti-inflammatory and Anti-Non-coding RNA research · 2026Article
- Targeted Therapy for Restoring CFTR Activity: From Experimental to Clinical Features.International journal of molecular sciences · 2026Review
- The New Landscape of Cystic Fibrosis in the Era of Highly Effective Cystic Fibrosis Transmembrane Conductance Regulator Modulator Therapy.Journal of mother and child · 2026Review
- Evaluating Long-Term Effectiveness of Cystic Fibrosis Modulator Therapies after Rapid Adoption: A Dual-Approach Study.Annals of the American Thoracic Society · 2026Article
- Transforming Care Models in Cystic Fibrosis: A Review.Healthcare (Basel, Switzerland) · 2025Review
- A Retrospective, Longitudinal Registry Study on the Long-Term Durability of Ivacaftor Treatment in People with Cystic Fibrosis.Pulmonary therapy · 2024Article
- CFTR Function Restoration upon Elexacaftor/Tezacaftor/Ivacaftor Treatment in Patient-Derived Intestinal Organoids with RareInternational journal of molecular sciences · 2023Article
38 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
9 authors at 7 institutions in 2 countries.
Funding
Abstract
backgroundIvacaftor has been previously assessed in patients with cystic fibrosis with Gly551Asp-CFTR or other gating mutations. We assessed ivacaftor in patients with Arg117His-CFTR, a residual function mutation.
methodsWe did a 24-week, placebo-controlled, double-blind, randomised clinical trial, which enrolled 69 patients with cystic fibrosis aged 6 years and older with Arg117His-CFTR and percentage of predicted forced expiratory volume in 1 s (% predicted FEV1) of at least 40. We randomly assigned eligible patients (1:1) to receive placebo or ivacaftor 150 mg every 12 h for 24 weeks. Randomisation was stratified by age (6-11, 12-17, and ≥18 years) and % predicted FEV1 (<70, ≥70 to ≤90, and >90). The primary outcome was the absolute change from baseline in % predicted FEV1 through week 24. Secondary outcomes included safety and changes in sweat chloride concentrations and Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory domain scores. An open-label extension enrolled 65 of the patients after washout; after 12 weeks, we did an interim analysis.
findingsAfter 24 weeks, the treatment difference in mean absolute change in % predicted FEV1 between ivacaftor (n=34) and placebo (n=35) was 2·1 percentage points (95% CI -1·13 to 5·35; p=0·20). Ivacaftor treatment resulted in significant treatment differences in sweat chloride (-24·0 mmol/L, 95% CI -28·01 to -19·93; p<0·0001) and CFQ-R respiratory domain (8·4, 2·17 to 14·61; p=0·009). In prespecified subgroup analyses, % predicted FEV1 significantly improved with ivacaftor in patients aged 18 years or older (treatment difference vs placebo: 5·0 percentage points, 95% CI 1·15 to 8·78; p=0·01), but not in patients aged 6-11 years (-6·3 percentage points, -11·96 to -0·71; p=0·03). In the extension study, both placebo-to-ivacaftor and ivacaftor-to-ivacaftor groups showed % predicted FEV1 improvement (absolute change from post-washout baseline at week 12: placebo-to-ivacaftor, 5·0 percentage points [p=0·0005]; ivacaftor-to-ivacaftor, 6·0 percentage points [p=0·006]). We did not identify any new safety concerns. The studies are registered with ClinicalTrials.gov (the randomised, placebo-controlled study, number NCT01614457; the open-label extension study, number NCT01707290).
interpretationAlthough this study did not show a significant improvement in % predicted FEV1, ivacaftor did significantly improve sweat chloride and CFQ-R respiratory domain scores and lung function in adult patients with Arg117His-CFTR, indicating that ivacaftor might benefit patients with Arg117His-CFTR who have established disease.
fundingVertex Pharmaceuticals Incorporated.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.