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Vonoprazan prevents ulcer recurrence during long-term NSAID therapy: randomised, lansoprazole-controlled non-inferiority and single-blind extension study
OBJECTIVE: To assess the non-inferiority of vonoprazan to lansoprazole for secondary prevention of non-steroidal anti-inflammatory drug (NSAID)-induced peptic ulcer (PU) and the safety of vonoprazan during extended use. DESIGN: A phase 3, 24-week, multicenter, randomised, double-blind (DB), active-c...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BMJ Publishing Group
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5969369/ https://www.ncbi.nlm.nih.gov/pubmed/28988197 http://dx.doi.org/10.1136/gutjnl-2017-314010 |
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author | Mizokami, Yuji Oda, Kazunori Funao, Nobuo Nishimura, Akira Soen, Satoshi Kawai, Takashi Ashida, Kiyoshi Sugano, Kentaro |
author_facet | Mizokami, Yuji Oda, Kazunori Funao, Nobuo Nishimura, Akira Soen, Satoshi Kawai, Takashi Ashida, Kiyoshi Sugano, Kentaro |
author_sort | Mizokami, Yuji |
collection | PubMed |
description | OBJECTIVE: To assess the non-inferiority of vonoprazan to lansoprazole for secondary prevention of non-steroidal anti-inflammatory drug (NSAID)-induced peptic ulcer (PU) and the safety of vonoprazan during extended use. DESIGN: A phase 3, 24-week, multicenter, randomised, double-blind (DB), active-controlled study, followed by a phase 3, ≥28 week, multicenter, single-blind, parallel-group extension study (EXT) in outpatients (n=642) receiving long-term NSAID therapy who are at risk of PU recurrence. The patients received vonoprazan (10 mg or 20 mg) or lansoprazole 15 mg once daily. For DB, non-inferiority of the proportion of patients with recurrent PU within 24 weeks was analysed by Farrington and Manning test (significance level 2.5%, non-inferiority margin 8.3%; primary endpoint), recurrent PU within 12 weeks, bleeding and time-to-event of PU (secondary endpoint) and treatment-emergent adverse events (TEAEs). For EXT, TEAEs (primary endpoint), recurrent PU and safety (secondary) were assessed up to 104 weeks for patients in the extension study. RESULTS: The non-inferiority of vonoprazan 10 mg and 20 mg to lansoprazole 15 mg was verified (percentage difference –2.2%,95% CI –6.2% to 1.8%, p<0.001; –2.1%,95% CI –6.1% to 2.0%, p<0.001, respectively). The proportion of patients with endoscopically confirmed recurrent PU within 24 weeks was 3.3%, 3.4% and 5.5%, for vonoprazan 10 mg, 20 mg and lansoprazole 15 mg, respectively. No significant safety concerns were identified. CONCLUSION: The non-inferiority of vonoprazan (10 and 20 mg) was verified in patients receiving long-term NSAIDs in DB; it was effective and well tolerated in EXT for longer than 1 year, with a safety profile similar to lansoprazole (15 mg). TRIAL REGISTRATION NUMBERS: NCT01452750, NCT01456260; Results. |
format | Online Article Text |
id | pubmed-5969369 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BMJ Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-59693692018-06-01 Vonoprazan prevents ulcer recurrence during long-term NSAID therapy: randomised, lansoprazole-controlled non-inferiority and single-blind extension study Mizokami, Yuji Oda, Kazunori Funao, Nobuo Nishimura, Akira Soen, Satoshi Kawai, Takashi Ashida, Kiyoshi Sugano, Kentaro Gut Peptic Ulcer OBJECTIVE: To assess the non-inferiority of vonoprazan to lansoprazole for secondary prevention of non-steroidal anti-inflammatory drug (NSAID)-induced peptic ulcer (PU) and the safety of vonoprazan during extended use. DESIGN: A phase 3, 24-week, multicenter, randomised, double-blind (DB), active-controlled study, followed by a phase 3, ≥28 week, multicenter, single-blind, parallel-group extension study (EXT) in outpatients (n=642) receiving long-term NSAID therapy who are at risk of PU recurrence. The patients received vonoprazan (10 mg or 20 mg) or lansoprazole 15 mg once daily. For DB, non-inferiority of the proportion of patients with recurrent PU within 24 weeks was analysed by Farrington and Manning test (significance level 2.5%, non-inferiority margin 8.3%; primary endpoint), recurrent PU within 12 weeks, bleeding and time-to-event of PU (secondary endpoint) and treatment-emergent adverse events (TEAEs). For EXT, TEAEs (primary endpoint), recurrent PU and safety (secondary) were assessed up to 104 weeks for patients in the extension study. RESULTS: The non-inferiority of vonoprazan 10 mg and 20 mg to lansoprazole 15 mg was verified (percentage difference –2.2%,95% CI –6.2% to 1.8%, p<0.001; –2.1%,95% CI –6.1% to 2.0%, p<0.001, respectively). The proportion of patients with endoscopically confirmed recurrent PU within 24 weeks was 3.3%, 3.4% and 5.5%, for vonoprazan 10 mg, 20 mg and lansoprazole 15 mg, respectively. No significant safety concerns were identified. CONCLUSION: The non-inferiority of vonoprazan (10 and 20 mg) was verified in patients receiving long-term NSAIDs in DB; it was effective and well tolerated in EXT for longer than 1 year, with a safety profile similar to lansoprazole (15 mg). TRIAL REGISTRATION NUMBERS: NCT01452750, NCT01456260; Results. BMJ Publishing Group 2018-06 2017-10-07 /pmc/articles/PMC5969369/ /pubmed/28988197 http://dx.doi.org/10.1136/gutjnl-2017-314010 Text en © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted. This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ |
spellingShingle | Peptic Ulcer Mizokami, Yuji Oda, Kazunori Funao, Nobuo Nishimura, Akira Soen, Satoshi Kawai, Takashi Ashida, Kiyoshi Sugano, Kentaro Vonoprazan prevents ulcer recurrence during long-term NSAID therapy: randomised, lansoprazole-controlled non-inferiority and single-blind extension study |
title | Vonoprazan prevents ulcer recurrence during long-term NSAID therapy: randomised, lansoprazole-controlled non-inferiority and single-blind extension study |
title_full | Vonoprazan prevents ulcer recurrence during long-term NSAID therapy: randomised, lansoprazole-controlled non-inferiority and single-blind extension study |
title_fullStr | Vonoprazan prevents ulcer recurrence during long-term NSAID therapy: randomised, lansoprazole-controlled non-inferiority and single-blind extension study |
title_full_unstemmed | Vonoprazan prevents ulcer recurrence during long-term NSAID therapy: randomised, lansoprazole-controlled non-inferiority and single-blind extension study |
title_short | Vonoprazan prevents ulcer recurrence during long-term NSAID therapy: randomised, lansoprazole-controlled non-inferiority and single-blind extension study |
title_sort | vonoprazan prevents ulcer recurrence during long-term nsaid therapy: randomised, lansoprazole-controlled non-inferiority and single-blind extension study |
topic | Peptic Ulcer |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5969369/ https://www.ncbi.nlm.nih.gov/pubmed/28988197 http://dx.doi.org/10.1136/gutjnl-2017-314010 |
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