FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2956839011> ?p ?o ?g. }

• W2956839011 endingPage "779" @default.
• W2956839011 startingPage "771" @default.
• W2956839011 abstract "Background A hallmark of idiopathic pulmonary fibrosis is the excess accumulation of extracellular matrix in the lungs. Degradation of extracellular matrix generates free-circulating protein fragments called neoepitopes. The aim of the INMARK trial was to investigate changes in neoepitopes as predictors of disease progression in patients with idiopathic pulmonary fibrosis and the effect of nintedanib on these biomarkers. Methods In this randomised, double-blind, placebo-controlled trial, patients with a diagnosis of idiopathic pulmonary fibrosis within the past 3 years and forced vital capacity (FVC) of 80% predicted or higher were eligible to participate. Patients were recruited from hospitals, private practices, clinical research units, and academic medical centres. Patients were randomly assigned (1:2) with the use of a pseudo-random number generator to receive oral nintedanib 150 mg twice a day or placebo for 12 weeks in a double-blind fashion, followed by open-label nintedanib for 40 weeks. The primary endpoint was the rate of change in C-reactive protein (CRP) degraded by matrix metalloproteinases 1 and 8 (CRPM) from baseline to week 12 in the intention-to-treat population. The trial has been completed and is registered with ClinicalTrials.gov, number NCT02788474, and with the European Clinical Trials Database, number 2015–003148–38. Findings Between June 27, 2016, and May 15, 2017, 347 patients were randomly assigned to the nintedanib group (n=116) or to the placebo group (n=231). One patient from the placebo group was not treated owing to a randomisation error. At baseline, mean FVC was 97·5% (SD 13·5) predicted. In the double-blind period, 116 patients received nintedanib and 230 patients received placebo. The rate of change in CRPM from baseline to week 12 was −2·57 × 10−3 ng/mL/month in the nintedanib group and −1·90 × 10−3 ng/mL/month in the placebo group (between-group difference −0·66 × 10−3 ng/mL/month [95% CI −6·21 × 10−3 to 4·88 × 10−3]; p=0·8146). The adjusted rate of change in FVC over 12 weeks was 5·9 mL in the nintedanib group and −70·2 mL in the placebo group (difference 76·1 mL/12 weeks [31·7 to 120·4]). In patients who received placebo for 12 weeks followed by open-label nintedanib, rising concentrations of CRPM over 12 weeks were associated with disease progression (absolute decline in FVC ≥10% predicted or death) over 52 weeks. In the double-blind period, serious adverse events were reported in eight (7%) patients given nintedanib and 18 (8%) patients given placebo. Grade 3 diarrhoea was reported in two (2%) patients in the nintedanib group and two (1%) patients in the placebo group. No patients had grade 4 diarrhoea. Interpretation In patients with idiopathic pulmonary fibrosis and preserved lung function, treatment with nintedanib versus placebo for 12 weeks did not affect the rate of change in CRPM but was associated with a reduced rate of decline in FVC. These results suggest that change in CRPM is not a marker of response to nintedanib in patients with idiopathic pulmonary fibrosis. Funding Boehringer Ingelheim. A hallmark of idiopathic pulmonary fibrosis is the excess accumulation of extracellular matrix in the lungs. Degradation of extracellular matrix generates free-circulating protein fragments called neoepitopes. The aim of the INMARK trial was to investigate changes in neoepitopes as predictors of disease progression in patients with idiopathic pulmonary fibrosis and the effect of nintedanib on these biomarkers. In this randomised, double-blind, placebo-controlled trial, patients with a diagnosis of idiopathic pulmonary fibrosis within the past 3 years and forced vital capacity (FVC) of 80% predicted or higher were eligible to participate. Patients were recruited from hospitals, private practices, clinical research units, and academic medical centres. Patients were randomly assigned (1:2) with the use of a pseudo-random number generator to receive oral nintedanib 150 mg twice a day or placebo for 12 weeks in a double-blind fashion, followed by open-label nintedanib for 40 weeks. The primary endpoint was the rate of change in C-reactive protein (CRP) degraded by matrix metalloproteinases 1 and 8 (CRPM) from baseline to week 12 in the intention-to-treat population. The trial has been completed and is registered with ClinicalTrials.gov, number NCT02788474, and with the European Clinical Trials Database, number 2015–003148–38. Between June 27, 2016, and May 15, 2017, 347 patients were randomly assigned to the nintedanib group (n=116) or to the placebo group (n=231). One patient from the placebo group was not treated owing to a randomisation error. At baseline, mean FVC was 97·5% (SD 13·5) predicted. In the double-blind period, 116 patients received nintedanib and 230 patients received placebo. The rate of change in CRPM from baseline to week 12 was −2·57 × 10−3 ng/mL/month in the nintedanib group and −1·90 × 10−3 ng/mL/month in the placebo group (between-group difference −0·66 × 10−3 ng/mL/month [95% CI −6·21 × 10−3 to 4·88 × 10−3]; p=0·8146). The adjusted rate of change in FVC over 12 weeks was 5·9 mL in the nintedanib group and −70·2 mL in the placebo group (difference 76·1 mL/12 weeks [31·7 to 120·4]). In patients who received placebo for 12 weeks followed by open-label nintedanib, rising concentrations of CRPM over 12 weeks were associated with disease progression (absolute decline in FVC ≥10% predicted or death) over 52 weeks. In the double-blind period, serious adverse events were reported in eight (7%) patients given nintedanib and 18 (8%) patients given placebo. Grade 3 diarrhoea was reported in two (2%) patients in the nintedanib group and two (1%) patients in the placebo group. No patients had grade 4 diarrhoea. In patients with idiopathic pulmonary fibrosis and preserved lung function, treatment with nintedanib versus placebo for 12 weeks did not affect the rate of change in CRPM but was associated with a reduced rate of decline in FVC. These results suggest that change in CRPM is not a marker of response to nintedanib in patients with idiopathic pulmonary fibrosis." @default.
• W2956839011 created "2019-07-23" @default.
• W2956839011 creator A5000309995 @default.
• W2956839011 creator A5002422862 @default.
• W2956839011 creator A5002731286 @default.
• W2956839011 creator A5005376778 @default.
• W2956839011 creator A5005533579 @default.
• W2956839011 creator A5006171435 @default.
• W2956839011 creator A5006650120 @default.
• W2956839011 creator A5006680780 @default.
• W2956839011 creator A5006969715 @default.
• W2956839011 creator A5007759921 @default.
• W2956839011 creator A5008888396 @default.
• W2956839011 creator A5009182420 @default.
• W2956839011 creator A5012574601 @default.
• W2956839011 creator A5012626608 @default.
• W2956839011 creator A5012726328 @default.
• W2956839011 creator A5013848299 @default.
• W2956839011 creator A5014377222 @default.
• W2956839011 creator A5014703126 @default.
• W2956839011 creator A5014766180 @default.
• W2956839011 creator A5015472121 @default.
• W2956839011 creator A5017900450 @default.
• W2956839011 creator A5021114610 @default.
• W2956839011 creator A5023577403 @default.
• W2956839011 creator A5024201886 @default.
• W2956839011 creator A5024611768 @default.
• W2956839011 creator A5024697965 @default.
• W2956839011 creator A5025137523 @default.
• W2956839011 creator A5025971915 @default.
• W2956839011 creator A5026135954 @default.
• W2956839011 creator A5026499895 @default.
• W2956839011 creator A5026818455 @default.
• W2956839011 creator A5026986582 @default.
• W2956839011 creator A5027241081 @default.
• W2956839011 creator A5027510239 @default.
• W2956839011 creator A5028121006 @default.
• W2956839011 creator A5030456446 @default.
• W2956839011 creator A5030988190 @default.
• W2956839011 creator A5031034216 @default.
• W2956839011 creator A5031057853 @default.
• W2956839011 creator A5033599838 @default.
• W2956839011 creator A5034180464 @default.
• W2956839011 creator A5035168811 @default.
• W2956839011 creator A5036018239 @default.
• W2956839011 creator A5036317882 @default.
• W2956839011 creator A5036588079 @default.
• W2956839011 creator A5038566673 @default.
• W2956839011 creator A5038983697 @default.
• W2956839011 creator A5039064134 @default.
• W2956839011 creator A5039973360 @default.
• W2956839011 creator A5040350185 @default.
• W2956839011 creator A5040472185 @default.
• W2956839011 creator A5041369504 @default.
• W2956839011 creator A5042561953 @default.
• W2956839011 creator A5043204832 @default.
• W2956839011 creator A5045010479 @default.
• W2956839011 creator A5045476442 @default.
• W2956839011 creator A5046379141 @default.
• W2956839011 creator A5046880805 @default.
• W2956839011 creator A5048144177 @default.
• W2956839011 creator A5053770230 @default.
• W2956839011 creator A5054842148 @default.
• W2956839011 creator A5055183282 @default.
• W2956839011 creator A5055570107 @default.
• W2956839011 creator A5055778507 @default.
• W2956839011 creator A5055981872 @default.
• W2956839011 creator A5059307916 @default.
• W2956839011 creator A5060426000 @default.
• W2956839011 creator A5063456842 @default.
• W2956839011 creator A5066873114 @default.
• W2956839011 creator A5067052172 @default.
• W2956839011 creator A5067998933 @default.
• W2956839011 creator A5069645289 @default.
• W2956839011 creator A5070498798 @default.
• W2956839011 creator A5071749570 @default.
• W2956839011 creator A5071985935 @default.
• W2956839011 creator A5072492631 @default.
• W2956839011 creator A5075075363 @default.
• W2956839011 creator A5075378562 @default.
• W2956839011 creator A5075747454 @default.
• W2956839011 creator A5075786921 @default.
• W2956839011 creator A5079519206 @default.
• W2956839011 creator A5079875398 @default.
• W2956839011 creator A5080112598 @default.
• W2956839011 creator A5083099312 @default.
• W2956839011 creator A5084259352 @default.
• W2956839011 creator A5084744867 @default.
• W2956839011 creator A5085453649 @default.
• W2956839011 creator A5085722313 @default.
• W2956839011 creator A5086416072 @default.
• W2956839011 creator A5086830418 @default.
• W2956839011 creator A5087279007 @default.
• W2956839011 creator A5087476255 @default.
• W2956839011 creator A5087519704 @default.
• W2956839011 creator A5087940641 @default.
• W2956839011 creator A5088253136 @default.
• W2956839011 creator A5088824087 @default.

• next