Trial reportThe New England journal of medicine2017
Tezacaftor-Ivacaftor in Residual-Function Heterozygotes with Cystic Fibrosis.
2 registry-linked trialsOpen access · bronzeAbstract readClinical Trial, Phase IIIMulticenter StudyRandomized Controlled Trial
In one paragraph
Trial report in The New England journal of medicine, 2017. 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 232 papers, 7 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
232citing papers in PubMed, 7 pooled it
45.0field-weighted citation impact, top 1% of its field
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, Crossover Study to Evaluate the Efficacy and Safety of Ivacaftor and VX-661 in Combination With Ivacaftor in Subjects Aged 12 Years and Older With Cystic Fibrosis, Heterozygous for the F508del-CFTR Mutation, and a Second Allele With a CFTR Mutation Predicted to Have Residual Function
Studying the Presence of CFRD Complications With Thoughtful Recruitment (SPeCTRuM)
Who cites it
232 citing papers in PubMed, 7 syntheses or guidelines pooled it, 508 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
- Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del).The Cochrane database of systematic reviews · 2023Pooled 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
- Efficacy and Safety of Triple Combination Cystic Fibrosis Transmembrane Conductance Regulator Modulators in Patients With Cystic Fibrosis: A Meta-Analysis of Randomized Controlled Trials.Frontiers in pharmacology · 2022Pooled it
- Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del).The Cochrane database of systematic reviews · 2020Pooled it
- 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
- Safety and efficacy of elexacaftor/tezacaftor/ivacaftor in adolescents and adults with cystic fibrosis and F508del-gating and F508del-residual function genotypes: results from an open-label extension study.Annals of the American Thoracic Society · 2026Trial
- Ivacaftor for Chronic Obstructive Pulmonary Disease: Results from a Phase 2, Randomized Controlled Trial.American journal of respiratory and critical care medicine · 2025Trial
- Long-term safety and efficacy of elexacaftor/tezacaftor/ivacaftor in people with cystic fibrosis and at least oneThe European respiratory journal · 2023Trial
- Efficacy and safety of inhaled ENaC inhibitor BI 1265162 in patients with cystic fibrosis: BALANCE-CF 1, a randomised, phase II study.The European respiratory journal · 2022Trial
- Triple Therapy for Cystic FibrosisThe New England journal of medicine · 2021Trial
- Tezacaftor/ivacaftor in people with cystic fibrosis who stopped lumacaftor/ivacaftor due to respiratory adverse events.Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society · 2021Trial
- Ivacaftor in People with Cystic Fibrosis and aAnnals of the American Thoracic Society · 2021Trial
- Elexacaftor-Tezacaftor-Ivacaftor for Cystic Fibrosis with a Single Phe508del Allele.The New England journal of medicine · 2019Trial
- An open-label extension study of ivacaftor in children with CF and a CFTR gating mutation initiating treatment at age 2-5 years (KLIMB).Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society · 2019Trial
- Elexacaftor-tezacaftor-ivacaftor for individuals with residual CFTR activity: an open-label, nonrandomized clinical trial.Annals of the American Thoracic Society · 2026Article
- Effects of elexacaftor/tezacaftor/ivacaftor on the nasal microbial metagenome in cystic fibrosis.Microbiology spectrum · 2026Article
- Targeted Therapy for Restoring CFTR Activity: From Experimental to Clinical Features.International journal of molecular sciences · 2026Review
- Cystic Fibrosis Mortality Trends 1999-2024-A CDC Wonder Study.Advances in respiratory medicine · 2026Article
172 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 8 institutions in 6 countries.
Steven M RoweFrom the Division of Pulmonary, Allergy, and Critical Care Medicine, University of Alabama at Birmingham, Birmingham (S.M.R.); the Arizona Respiratory Center, University of Arizona, Tucson (C.D.); the Department of Respiratory Medicine, Hannover Medical School, and the German Center for Lung Research, Hannover, Germany (F.C.R.); Hadassah Hebrew University Medical Center, Jerusalem, Israel (E.K.); Alfred Health, Melbourne, VIC, Australia (J.W.); St. Michael's Hospital, Toronto (E.T.); Vertex Pharmaceuticals, Boston (N.N., C.S., L.H., E.P.I., C.M., J.L.-H.); and Imperial College and Royal Brompton and Harefield NHS Foundation Trust, London (J.C.D.).
Cori DainesFrom the Division of Pulmonary, Allergy, and Critical Care Medicine, University of Alabama at Birmingham, Birmingham (S.M.R.); the Arizona Respiratory Center, University of Arizona, Tucson (C.D.); the Department of Respiratory Medicine, Hannover Medical School, and the German Center for Lung Research, Hannover, Germany (F.C.R.); Hadassah Hebrew University Medical Center, Jerusalem, Israel (E.K.); Alfred Health, Melbourne, VIC, Australia (J.W.); St. Michael's Hospital, Toronto (E.T.); Vertex Pharmaceuticals, Boston (N.N., C.S., L.H., E.P.I., C.M., J.L.-H.); and Imperial College and Royal Brompton and Harefield NHS Foundation Trust, London (J.C.D.).
Felix C RingshausenFrom the Division of Pulmonary, Allergy, and Critical Care Medicine, University of Alabama at Birmingham, Birmingham (S.M.R.); the Arizona Respiratory Center, University of Arizona, Tucson (C.D.); the Department of Respiratory Medicine, Hannover Medical School, and the German Center for Lung Research, Hannover, Germany (F.C.R.); Hadassah Hebrew University Medical Center, Jerusalem, Israel (E.K.); Alfred Health, Melbourne, VIC, Australia (J.W.); St. Michael's Hospital, Toronto (E.T.); Vertex Pharmaceuticals, Boston (N.N., C.S., L.H., E.P.I., C.M., J.L.-H.); and Imperial College and Royal Brompton and Harefield NHS Foundation Trust, London (J.C.D.).
Eitan KeremFrom the Division of Pulmonary, Allergy, and Critical Care Medicine, University of Alabama at Birmingham, Birmingham (S.M.R.); the Arizona Respiratory Center, University of Arizona, Tucson (C.D.); the Department of Respiratory Medicine, Hannover Medical School, and the German Center for Lung Research, Hannover, Germany (F.C.R.); Hadassah Hebrew University Medical Center, Jerusalem, Israel (E.K.); Alfred Health, Melbourne, VIC, Australia (J.W.); St. Michael's Hospital, Toronto (E.T.); Vertex Pharmaceuticals, Boston (N.N., C.S., L.H., E.P.I., C.M., J.L.-H.); and Imperial College and Royal Brompton and Harefield NHS Foundation Trust, London (J.C.D.).
John WilsonFrom the Division of Pulmonary, Allergy, and Critical Care Medicine, University of Alabama at Birmingham, Birmingham (S.M.R.); the Arizona Respiratory Center, University of Arizona, Tucson (C.D.); the Department of Respiratory Medicine, Hannover Medical School, and the German Center for Lung Research, Hannover, Germany (F.C.R.); Hadassah Hebrew University Medical Center, Jerusalem, Israel (E.K.); Alfred Health, Melbourne, VIC, Australia (J.W.); St. Michael's Hospital, Toronto (E.T.); Vertex Pharmaceuticals, Boston (N.N., C.S., L.H., E.P.I., C.M., J.L.-H.); and Imperial College and Royal Brompton and Harefield NHS Foundation Trust, London (J.C.D.).
Elizabeth TullisFrom the Division of Pulmonary, Allergy, and Critical Care Medicine, University of Alabama at Birmingham, Birmingham (S.M.R.); the Arizona Respiratory Center, University of Arizona, Tucson (C.D.); the Department of Respiratory Medicine, Hannover Medical School, and the German Center for Lung Research, Hannover, Germany (F.C.R.); Hadassah Hebrew University Medical Center, Jerusalem, Israel (E.K.); Alfred Health, Melbourne, VIC, Australia (J.W.); St. Michael's Hospital, Toronto (E.T.); Vertex Pharmaceuticals, Boston (N.N., C.S., L.H., E.P.I., C.M., J.L.-H.); and Imperial College and Royal Brompton and Harefield NHS Foundation Trust, London (J.C.D.).
Nitin NairFrom the Division of Pulmonary, Allergy, and Critical Care Medicine, University of Alabama at Birmingham, Birmingham (S.M.R.); the Arizona Respiratory Center, University of Arizona, Tucson (C.D.); the Department of Respiratory Medicine, Hannover Medical School, and the German Center for Lung Research, Hannover, Germany (F.C.R.); Hadassah Hebrew University Medical Center, Jerusalem, Israel (E.K.); Alfred Health, Melbourne, VIC, Australia (J.W.); St. Michael's Hospital, Toronto (E.T.); Vertex Pharmaceuticals, Boston (N.N., C.S., L.H., E.P.I., C.M., J.L.-H.); and Imperial College and Royal Brompton and Harefield NHS Foundation Trust, London (J.C.D.).
Christopher SimardFrom the Division of Pulmonary, Allergy, and Critical Care Medicine, University of Alabama at Birmingham, Birmingham (S.M.R.); the Arizona Respiratory Center, University of Arizona, Tucson (C.D.); the Department of Respiratory Medicine, Hannover Medical School, and the German Center for Lung Research, Hannover, Germany (F.C.R.); Hadassah Hebrew University Medical Center, Jerusalem, Israel (E.K.); Alfred Health, Melbourne, VIC, Australia (J.W.); St. Michael's Hospital, Toronto (E.T.); Vertex Pharmaceuticals, Boston (N.N., C.S., L.H., E.P.I., C.M., J.L.-H.); and Imperial College and Royal Brompton and Harefield NHS Foundation Trust, London (J.C.D.).
Linda HanFrom the Division of Pulmonary, Allergy, and Critical Care Medicine, University of Alabama at Birmingham, Birmingham (S.M.R.); the Arizona Respiratory Center, University of Arizona, Tucson (C.D.); the Department of Respiratory Medicine, Hannover Medical School, and the German Center for Lung Research, Hannover, Germany (F.C.R.); Hadassah Hebrew University Medical Center, Jerusalem, Israel (E.K.); Alfred Health, Melbourne, VIC, Australia (J.W.); St. Michael's Hospital, Toronto (E.T.); Vertex Pharmaceuticals, Boston (N.N., C.S., L.H., E.P.I., C.M., J.L.-H.); and Imperial College and Royal Brompton and Harefield NHS Foundation Trust, London (J.C.D.).
Edward P IngenitoFrom the Division of Pulmonary, Allergy, and Critical Care Medicine, University of Alabama at Birmingham, Birmingham (S.M.R.); the Arizona Respiratory Center, University of Arizona, Tucson (C.D.); the Department of Respiratory Medicine, Hannover Medical School, and the German Center for Lung Research, Hannover, Germany (F.C.R.); Hadassah Hebrew University Medical Center, Jerusalem, Israel (E.K.); Alfred Health, Melbourne, VIC, Australia (J.W.); St. Michael's Hospital, Toronto (E.T.); Vertex Pharmaceuticals, Boston (N.N., C.S., L.H., E.P.I., C.M., J.L.-H.); and Imperial College and Royal Brompton and Harefield NHS Foundation Trust, London (J.C.D.).
Charlotte McKeeFrom the Division of Pulmonary, Allergy, and Critical Care Medicine, University of Alabama at Birmingham, Birmingham (S.M.R.); the Arizona Respiratory Center, University of Arizona, Tucson (C.D.); the Department of Respiratory Medicine, Hannover Medical School, and the German Center for Lung Research, Hannover, Germany (F.C.R.); Hadassah Hebrew University Medical Center, Jerusalem, Israel (E.K.); Alfred Health, Melbourne, VIC, Australia (J.W.); St. Michael's Hospital, Toronto (E.T.); Vertex Pharmaceuticals, Boston (N.N., C.S., L.H., E.P.I., C.M., J.L.-H.); and Imperial College and Royal Brompton and Harefield NHS Foundation Trust, London (J.C.D.).
Julie Lekstrom-HimesFrom the Division of Pulmonary, Allergy, and Critical Care Medicine, University of Alabama at Birmingham, Birmingham (S.M.R.); the Arizona Respiratory Center, University of Arizona, Tucson (C.D.); the Department of Respiratory Medicine, Hannover Medical School, and the German Center for Lung Research, Hannover, Germany (F.C.R.); Hadassah Hebrew University Medical Center, Jerusalem, Israel (E.K.); Alfred Health, Melbourne, VIC, Australia (J.W.); St. Michael's Hospital, Toronto (E.T.); Vertex Pharmaceuticals, Boston (N.N., C.S., L.H., E.P.I., C.M., J.L.-H.); and Imperial College and Royal Brompton and Harefield NHS Foundation Trust, London (J.C.D.).
Jane C DaviesFrom the Division of Pulmonary, Allergy, and Critical Care Medicine, University of Alabama at Birmingham, Birmingham (S.M.R.); the Arizona Respiratory Center, University of Arizona, Tucson (C.D.); the Department of Respiratory Medicine, Hannover Medical School, and the German Center for Lung Research, Hannover, Germany (F.C.R.); Hadassah Hebrew University Medical Center, Jerusalem, Israel (E.K.); Alfred Health, Melbourne, VIC, Australia (J.W.); St. Michael's Hospital, Toronto (E.T.); Vertex Pharmaceuticals, Boston (N.N., C.S., L.H., E.P.I., C.M., J.L.-H.); and Imperial College and Royal Brompton and Harefield NHS Foundation Trust, London (J.C.D.).
Vertex Pharmaceuticals (United States) · USAlfred Health · AUGerman Center for Lung Research · DEHadassah Medical Center · ILRoyal Brompton & Harefield NHS Foundation Trust · GBSt Michael’s Hospital · IEUniversity of Alabama at Birmingham · USUniversity of Arizona · US
Funding
UAB CF Research and Translation Core CenterP30DK072482 · NIDDK · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI Brian R. Davis · 2007 to 2026
$23.0MTranslational Program in CFTR-Related Airway DiseasesR35HL135816 · NHLBI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI ROWE, STEVEN MARK · 2017 to 2022
$6.3MUAB Center for Clinical and Translational Science (CCTS)U54TR001005 · NCATS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI KIMBERLY, ROBERT P. · 2014 to 2014
$4.6MNCATS NIH HHS U54 TR001005NHLBI NIH HHS R35 HL135816NIDDK NIH HHS P30 DK072482
Abstract
backgroundCystic fibrosis is an autosomal recessive disease caused by mutations in the CFTR gene that lead to progressive respiratory decline. Some mutant CFTR proteins show residual function and respond to the CFTR potentiator ivacaftor in vitro, whereas ivacaftor alone does not restore activity to Phe508del mutant CFTR.
methodsWe conducted a randomized, double-blind, placebo-controlled, phase 3, crossover trial to evaluate the efficacy and safety of ivacaftor alone or in combination with tezacaftor, a CFTR corrector, in 248 patients 12 years of age or older who had cystic fibrosis and were heterozygous for the Phe508del mutation and a CFTR mutation associated with residual CFTR function. Patients were randomly assigned to one of six sequences, each involving two 8-week intervention periods separated by an 8-week washout period. They received tezacaftor-ivacaftor, ivacaftor monotherapy, or placebo. The primary end point was the absolute change in the percentage of predicted forced expiratory volume in 1 second (FEV
resultsThe number of analyzed intervention periods was 162 for tezacaftor-ivacaftor, 157 for ivacaftor alone, and 162 for placebo. The least-squares mean difference versus placebo with respect to the absolute change in the percentage of predicted FEV
conclusionsCFTR modulator therapy with tezacaftor-ivacaftor or ivacaftor alone was efficacious in patients with cystic fibrosis who were heterozygous for the Phe508del deletion and a CFTR residual-function mutation. (Funded by Vertex Pharmaceuticals and others; EXPAND ClinicalTrials.gov number, NCT02392234 .).
Indexed as
AdolescentAdultAminophenolsBenzodioxolesChildCross-Over StudiesCystic FibrosisCystic Fibrosis Transmembrane Conductance RegulatorDouble-Blind MethodDrug CombinationsFemaleForced Expiratory VolumeHeterozygoteHumansIndolesMaleAminophenolsBenzodioxolesCFTR protein, humanCystic Fibrosis Transmembrane Conductance RegulatorDrug CombinationsIndolesivacaftorQuinolonestezacaftor
Identifiers
What OpenQuestion holds
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Registered trials
NCT02392234ClinicalTrials.gov
NCT06837181ClinicalTrials.gov
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.