Protocol for the RETHINK study: a randomised, double-blind, parallel-group, non-inferiority clinical trial comparing acetaminophen and NSAIDs for treatment of chronic pain in elderly patients with osteoarthritis of the hip and knee

Introduction In patients with chronic pain, oral analgesics are essential treatment options to manage pain appropriately, improve activities of daily living abilities and achieve a higher quality of life (QOL). It is desirable to select analgesics for elderly patients based on comparative data on an...

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Main Authors: Tempei Miyaji, Mototsugu Shimokawa, Hiroyuki Aono, Sadamoto Zenda, Makoto Endo, Yasuharu Nakashima, TOSHIHIKO HARA, Shinya Kawahara, Taishi Sato, Masami Tokunaga, Taro Mawatari, Tsutomu Kawano, Sanae Sakamoto, Toshio Takano, Masumi Miyake
Format: Article
Language:English
Published: BMJ Publishing Group 2023-02-01
Series:BMJ Open
Online Access:https://bmjopen.bmj.com/content/13/2/e068220.full
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author Tempei Miyaji
Mototsugu Shimokawa
Hiroyuki Aono
Sadamoto Zenda
Makoto Endo
Yasuharu Nakashima
TOSHIHIKO HARA
Shinya Kawahara
Taishi Sato
Masami Tokunaga
Taro Mawatari
Tsutomu Kawano
Sanae Sakamoto
Toshio Takano
Masumi Miyake
author_facet Tempei Miyaji
Mototsugu Shimokawa
Hiroyuki Aono
Sadamoto Zenda
Makoto Endo
Yasuharu Nakashima
TOSHIHIKO HARA
Shinya Kawahara
Taishi Sato
Masami Tokunaga
Taro Mawatari
Tsutomu Kawano
Sanae Sakamoto
Toshio Takano
Masumi Miyake
author_sort Tempei Miyaji
collection DOAJ
description Introduction In patients with chronic pain, oral analgesics are essential treatment options to manage pain appropriately, improve activities of daily living abilities and achieve a higher quality of life (QOL). It is desirable to select analgesics for elderly patients based on comparative data on analgesic effect and risk of adverse events; however, there are few comparative studies so far. The purpose of this study is to determine whether the efficacy and safety of acetaminophen are non-inferior to non-steroidal anti-inflammatory drugs (NSAIDs) in the treatment of chronic pain associated with osteoarthritis of the hip and knee in elderly patients.Methods and analysis This study is a multicentre, randomised controlled, double-blind, parallel-group study to compare the analgesic effect and adverse events between acetaminophen or NSAIDs (loxoprofen or celecoxib). A total of 400 elderly patients with osteoarthritis of the hip and knee will be recruited from five institutions in Japan. Patients of 65 years or older with osteoarthritis-related pain will be registered and randomly assigned to acetaminophen, loxoprofen or celecoxib with 2:1:1 allocation. The primary endpoint is change in the Brief Pain Inventory (BPI) item 3 (worst pain) score from baseline to week 8. The secondary endpoints are BPI item 3 score change from baseline to week 4, health-related QOL measured by Short Form-8 Health Survey, and occurrence of adverse events including gastrointestinal disorders and abnormal liver function. Data will be analysed in accordance with a predefined statistical analysis plan.Ethics and dissemination This study protocol was approved by the Kyushu University Hospital Certified Institutional Review Board for Clinical Trials on 28 January 2021 (KD2020004) and the chief executive of each participating hospital. The results of the study will be submitted to international peer-reviewed journals, and the main findings will be presented at international scientific conferences.Trial registration number jRCTs071200112.
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spelling doaj-art-52e9c78a7de14a5b86bb4eca36c3eeeb2025-08-20T03:16:36ZengBMJ Publishing GroupBMJ Open2044-60552023-02-0113210.1136/bmjopen-2022-068220Protocol for the RETHINK study: a randomised, double-blind, parallel-group, non-inferiority clinical trial comparing acetaminophen and NSAIDs for treatment of chronic pain in elderly patients with osteoarthritis of the hip and kneeTempei Miyaji0Mototsugu Shimokawa1Hiroyuki Aono2Sadamoto Zenda3Makoto Endo4Yasuharu Nakashima5TOSHIHIKO HARA6Shinya Kawahara7Taishi Sato8Masami Tokunaga9Taro Mawatari10Tsutomu Kawano11Sanae Sakamoto12Toshio Takano13Masumi Miyake14Department of Clinical Trial Data Management, Graduate School of Medicine, The University of Tokyo, Tokyo, JapanDepartment of Biostatistics, Yamaguchi University Graduate School of Medicine, Ube, Japan5 Research and Development Department, AYUMI Pharmaceutical Corporation, Chuo-ku, Tokyo, JapanDepartment of Radiation Oncology, National Cancer Centre Hospital East, Kashiwa, Chiba, JapanDepartment of Orthopaedic Surgery, Kyushu University, Fukuoka, JapanDepartment of Orthopaedic Surgery, Kyushu University, Fukuoka, JapanDepartment of Orthopaedic Surgery, Aso Iizuka Hospital, Iizuka, Fukuoka, JapanDepartment of Orthopaedic Surgery, Kyushu University, Fukuoka, JapanDepartment of Orthopaedic Surgery, Kyushu University, Fukuoka, JapanDepartment of Orthopaedic Surgery, Fukuoka Orthopaedic Hospital, Fukuoka, JapanDepartment of Orthopaedic Surgery, Hamanomachi Hospital, Fukuoka, JapanDepartment of Orthopaedic Surgery, Kyushu Rosai Hospital, Kitakyushu, Fukuoka, JapanFukuoka Data Centre of Clinical Trials, Fukuoka, JapanAyumi Pharmaceutical Corporation, Tokyo, JapanAyumi Pharmaceutical Corporation, Tokyo, JapanIntroduction In patients with chronic pain, oral analgesics are essential treatment options to manage pain appropriately, improve activities of daily living abilities and achieve a higher quality of life (QOL). It is desirable to select analgesics for elderly patients based on comparative data on analgesic effect and risk of adverse events; however, there are few comparative studies so far. The purpose of this study is to determine whether the efficacy and safety of acetaminophen are non-inferior to non-steroidal anti-inflammatory drugs (NSAIDs) in the treatment of chronic pain associated with osteoarthritis of the hip and knee in elderly patients.Methods and analysis This study is a multicentre, randomised controlled, double-blind, parallel-group study to compare the analgesic effect and adverse events between acetaminophen or NSAIDs (loxoprofen or celecoxib). A total of 400 elderly patients with osteoarthritis of the hip and knee will be recruited from five institutions in Japan. Patients of 65 years or older with osteoarthritis-related pain will be registered and randomly assigned to acetaminophen, loxoprofen or celecoxib with 2:1:1 allocation. The primary endpoint is change in the Brief Pain Inventory (BPI) item 3 (worst pain) score from baseline to week 8. The secondary endpoints are BPI item 3 score change from baseline to week 4, health-related QOL measured by Short Form-8 Health Survey, and occurrence of adverse events including gastrointestinal disorders and abnormal liver function. Data will be analysed in accordance with a predefined statistical analysis plan.Ethics and dissemination This study protocol was approved by the Kyushu University Hospital Certified Institutional Review Board for Clinical Trials on 28 January 2021 (KD2020004) and the chief executive of each participating hospital. The results of the study will be submitted to international peer-reviewed journals, and the main findings will be presented at international scientific conferences.Trial registration number jRCTs071200112.https://bmjopen.bmj.com/content/13/2/e068220.full
spellingShingle Tempei Miyaji
Mototsugu Shimokawa
Hiroyuki Aono
Sadamoto Zenda
Makoto Endo
Yasuharu Nakashima
TOSHIHIKO HARA
Shinya Kawahara
Taishi Sato
Masami Tokunaga
Taro Mawatari
Tsutomu Kawano
Sanae Sakamoto
Toshio Takano
Masumi Miyake
Protocol for the RETHINK study: a randomised, double-blind, parallel-group, non-inferiority clinical trial comparing acetaminophen and NSAIDs for treatment of chronic pain in elderly patients with osteoarthritis of the hip and knee
BMJ Open
title Protocol for the RETHINK study: a randomised, double-blind, parallel-group, non-inferiority clinical trial comparing acetaminophen and NSAIDs for treatment of chronic pain in elderly patients with osteoarthritis of the hip and knee
title_full Protocol for the RETHINK study: a randomised, double-blind, parallel-group, non-inferiority clinical trial comparing acetaminophen and NSAIDs for treatment of chronic pain in elderly patients with osteoarthritis of the hip and knee
title_fullStr Protocol for the RETHINK study: a randomised, double-blind, parallel-group, non-inferiority clinical trial comparing acetaminophen and NSAIDs for treatment of chronic pain in elderly patients with osteoarthritis of the hip and knee
title_full_unstemmed Protocol for the RETHINK study: a randomised, double-blind, parallel-group, non-inferiority clinical trial comparing acetaminophen and NSAIDs for treatment of chronic pain in elderly patients with osteoarthritis of the hip and knee
title_short Protocol for the RETHINK study: a randomised, double-blind, parallel-group, non-inferiority clinical trial comparing acetaminophen and NSAIDs for treatment of chronic pain in elderly patients with osteoarthritis of the hip and knee
title_sort protocol for the rethink study a randomised double blind parallel group non inferiority clinical trial comparing acetaminophen and nsaids for treatment of chronic pain in elderly patients with osteoarthritis of the hip and knee
url https://bmjopen.bmj.com/content/13/2/e068220.full
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