{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T14:09:07Z","timestamp":1790258947230,"version":"4.1.0"},"reference-count":21,"publisher":"BMJ","issue":"9","license":[{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"content-version":"unspecified","delay-in-days":23,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Hunan Provincial Key Research and Development Program","award":["(No. 2024JK2130"],"award-info":[{"award-number":["(No. 2024JK2130"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2026,8,13]]},"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Knee osteoarthritis (KOA) is a prevalent chronic degenerative joint disorder that seriously affects mobility and quality of life in older adults. Pharmacological treatments such as celecoxib are commonly used for symptom relief, but their long-term use may be limited by adverse effects. Acupuncture has been widely used as a complementary non-pharmacological treatment for KOA and may help reduce pain and improve function; however, its onset of benefit may be relatively gradual. Combining acupuncture-related integrative therapy with celecoxib may provide more rapid symptom relief while potentially improving sustained clinical outcomes and reducing reliance on prolonged pharmacological treatment. This study aims to evaluate the comparative effectiveness and safety of acupuncture-related integrative therapy, celecoxib and their combination in patients with KOA in a multicentre randomised controlled trial.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>This is a multicentre, three-arm, parallel-group randomised controlled trial that will be conducted in three hospitals in Hunan Province, China. A total of 282 participants with KOA will be randomly assigned in a 1:1:1 ratio to receive acupuncture-related integrative therapy, celecoxib therapy or combined acupuncture-related integrative therapy and celecoxib for 4 weeks, with an additional 4-week follow-up period. The primary outcome is the change in Visual Analogue Scale score for activity-related knee pain from baseline to week 4. Secondary outcomes include the Western Ontario and McMaster Universities Osteoarthritis Index, clinical response rate, knee range of motion, 30-second chair-stand test, 40-metre fast-paced walk test and incidence of adverse events. Outcome assessments will be conducted at baseline, week 2, week 4 and week 8. Safety will be monitored throughout. Data will be analysed using the intention-to-treat principle.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>The study has been approved by the ethics committees of all centres (HN-LL-KY-2025-007-01, 2025-KY-019-01, 2025042705). The study findings will be disseminated through publication in peer-reviewed journals and presentations at national or international academic conferences.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>ITMCTR2026000093. Registered on 5 December 2025. The first participant was recruited on 27 February 2026.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2026-124004","type":"journal-article","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T13:50:43Z","timestamp":1790257843000},"page":"e124004","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Randomised comparative effectiveness trial evaluating the efficacy and safety of acupuncture-related integrative therapy combined with celecoxib for chronic pain in patients with knee osteoarthritis: protocol"],"prefix":"10.1136","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-4939-733X","authenticated-orcid":false,"given":"Xinran","family":"Xiao","sequence":"first","affiliation":[{"name":"School of Acupuncture-Moxibustion, Tuina and Rehabilitation, Hunan University of Chinese Medicine, Changsha, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saiyang","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Acupuncture-Moxibustion, Tuina and Rehabilitation, Hunan University of Chinese Medicine, Changsha, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anzhe","family":"Tian","sequence":"additional","affiliation":[{"name":"School of Acupuncture-Moxibustion, Tuina and Rehabilitation, Hunan University of Chinese Medicine, Changsha, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Guo","sequence":"additional","affiliation":[{"name":"School of Acupuncture-Moxibustion, Tuina and Rehabilitation, Hunan University of Chinese Medicine, Changsha, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Acupuncture-Moxibustion, Tuina and Rehabilitation, Hunan University of Chinese Medicine, Changsha, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhixian","family":"Gong","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Hunan University of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Zhong","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Hunan University of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Zhang","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Hunan University of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiai","family":"Liu","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital of Hunan University of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang","family":"She","sequence":"additional","affiliation":[{"name":"Changsha Hospital of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Honghua","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Nursing, Hunan University of Chinese Medicine, Changsha, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2543-9258","authenticated-orcid":false,"given":"Mailan","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Acupuncture-Moxibustion, Tuina and Rehabilitation, Hunan University of Chinese Medicine, Changsha, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2026,9,24]]},"reference":[{"key":"2026092406502829000_16.9.e124004.1","doi-asserted-by":"crossref","DOI":"10.1186\/s13018-025-06140-0","article-title":"Global, regional, and national burden of knee osteoarthritis: findings from the Global Burden of Disease study 2021 and projections to 2045","volume":"20","author":"Ouyang","year":"2025","journal-title":"J Orthop Surg Res"},{"key":"2026092406502829000_16.9.e124004.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2024.07.014"},{"key":"2026092406502829000_16.9.e124004.3","doi-asserted-by":"crossref","first-page":"2841","DOI":"10.1097\/j.pain.0000000000001975","article-title":"Pain trajectory defines knee osteoarthritis subgroups: a prospective observational study","volume":"161","author":"Radoj\u010di\u0107","year":"2020","journal-title":"Pain"},{"key":"2026092406502829000_16.9.e124004.4","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1002\/acr.24131","article-title":"2019 American College of Rheumatology\/Arthritis Foundation Guideline for the Management of Osteoarthritis of the Hand, Hip, and Knee","volume":"72","author":"Kolasinski","year":"2020","journal-title":"Arthritis Care Res (Hoboken)"},{"key":"2026092406502829000_16.9.e124004.5","doi-asserted-by":"publisher","DOI":"10.1001\/jama.287.1.64"},{"key":"2026092406502829000_16.9.e124004.6","first-page":"355","article-title":"Effect and safety of acupotomy in treatment of knee osteoarthritis: a systematic review and Meta-analysis","volume":"40","author":"Fang","year":"2020","journal-title":"J Tradit Chin Med"},{"key":"2026092406502829000_16.9.e124004.7","doi-asserted-by":"crossref","DOI":"10.3390\/vetsci8080149","article-title":"Research Progress on the Mechanism of the Acupuncture Regulating Neuro-Endocrine-Immune Network System","volume":"8","author":"Cui","year":"2021","journal-title":"Vet Sci"},{"key":"2026092406502829000_16.9.e124004.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpain.2017.11.005"},{"key":"2026092406502829000_16.9.e124004.9","doi-asserted-by":"crossref","DOI":"10.1186\/s13075-019-1899-6","article-title":"Effects of intensity of electroacupuncture on chronic pain in patients with knee osteoarthritis: a randomized controlled trial","volume":"21","author":"Lv","year":"2019","journal-title":"Arthritis Res Ther"},{"key":"2026092406502829000_16.9.e124004.10","first-page":"2254","article-title":"Clinical Observation on Treatment of Knee Osteoarthritis with Three-Unblocking Acupuncture Based on TLR4\/NF-\u03baB Axis","volume":"18","author":"Wang","year":"2023","journal-title":"World J Integr Tradit West Med"},{"key":"2026092406502829000_16.9.e124004.11","doi-asserted-by":"crossref","first-page":"3211","DOI":"10.2147\/JPR.S186000","article-title":"Safety of celecoxib versus traditional nonsteroidal anti-inflammatory drugs in older patients with arthritis","volume":"11","author":"Shin","year":"2018","journal-title":"J Pain Res"},{"key":"2026092406502829000_16.9.e124004.12","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780290816"},{"key":"2026092406502829000_16.9.e124004.13","first-page":"323","article-title":"Chinese guidelines for diagnosis and treatment of osteoarthritis (2024 edition)","volume":"20","author":"Huang","year":"2024","journal-title":"Chin J Painol"},{"key":"2026092406502829000_16.9.e124004.14","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(74)90884-8"},{"key":"2026092406502829000_16.9.e124004.15","first-page":"57","article-title":"The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) in Persian Speaking Patients with Knee Osteoarthritis","volume":"2","author":"Ebrahimzadeh","year":"2014","journal-title":"Arch Bone Jt Surg"},{"key":"2026092406502829000_16.9.e124004.16","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2004.022905"},{"key":"2026092406502829000_16.9.e124004.17","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2013.05.002"},{"key":"2026092406502829000_16.9.e124004.18","first-page":"730","article-title":"Effect of different electroacupuncture intensities on chronic pain in patients with knee osteoarthritis","volume":"42","author":"Li","year":"2023","journal-title":"Shanghai Journal of Acupuncture and Moxibustion"},{"key":"2026092406502829000_16.9.e124004.19","unstructured":"Liu YF . Knee Joint Function and Quality of Life Improvements of Electro-acupuncture Combined with Celecoxib for Patients with Early Knee Osteoarthritis.Journal of Sichuan of Traditional Chinese Medicine. 2018;36:201\u20133."},{"key":"2026092406502829000_16.9.e124004.20","first-page":"1364","article-title":"Functional Status, and Quality of Life in Individuals With Knee Osteoarthritis","volume":"21","author":"Aydemir","year":"2023","journal-title":"J Manipulative Physiol Ther"},{"key":"2026092406502829000_16.9.e124004.21","doi-asserted-by":"crossref","first-page":"3003","DOI":"10.1007\/s10067-025-07497-7","article-title":"Clinical efficacy of fire-needle warming therapy in the treatment of knee osteoarthritis of cold-dampness type and its effect on serum IL-1\u03b2 and MMP-3","volume":"44","author":"Liu","year":"2025","journal-title":"Clin Rheumatol"}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2026-124004","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T13:50:48Z","timestamp":1790257848000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2026-124004"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9]]},"references-count":21,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9,24]]},"published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1136\/bmjopen-2026-124004"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2026-124004","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"value":"2044-6055","type":"print"},{"value":"2044-6055","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9]]}}}