Duloxetine combined with intra-articular injection versus intra-articular injection alone for pain relief in knee osteoarthritis: a study protocol for a randomised controlled trial

Duo Yi Li, Rong Han, Zhi Gang Zhao, Fang Luo, Duo Yi Li, Rong Han, Zhi Gang Zhao, Fang Luo

Abstract

Introduction: Intra-articular (IA) injection of hyaluronic acid (HA) and corticosteroid (CS) is a common treatment for osteoarthritis (OA) of the knee. As a drug treatment for patients with depression, duloxetine has been shown in many studies to effectively relieve the pain of OA and improve function of the knee joint. However, evidence regarding the efficacy of IA injection of HA+CS combined with duloxetine for pain management in patients with OA of the knee is lacking. The aim of this study was to test the hypothesis that IA injection of HA+CS combined with duloxetine could achieve pain management superior to that of IA injection of HA+CS alone in patients experiencing knee OA pain.

Methods: This study will adopt a prospective, randomised, open-label blind endpoint study design. In total, 150 patients with OA of the knee will be enrolled in the study. The participants will be randomly allocated to receive either a single IA injection of HA+CS combined with duloxetine or a single IA injection of HA+CS alone, and both groups will complete a 24-week follow-up to assess pain and functional improvements. The primary outcome measure is the change in the weekly mean of the 24 hours average pain scores from baseline to the end of 24 weeks in patients with OA of the knee, and the secondary outcomes include the response to treatment, changes from baseline in the brief pain inventory, improvement in the Western Ontario and McMaster Universities Osteoarthritis index scores, patient global impression of improvement scale, Hospital Anxiety and Depression Scale and adverse events during the 24-week follow-up. The data will be analysed by the intention-to-treat principle.

Ethics approval and dissemination: This study was approved by the institutional ethics committee of the Beijing Tiantan Hospital (approval number: KY 2019-086-02). The results of the study will be published in peer-reviewed journals, and the findings will be presented at scientific meetings.

Trial registration number: ClinicalTrials.gov Identifier: NCT04117893; Pre-results.

Keywords: anaesthetics; knee; pain management.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Trial design of the treatment for knee osteoarthritis. BPI, brief pain inventory; CS, corticosteroids; HA, hyaluronic acid; HADS, hospital anxiety and depression scale; IA, intra-articular; NSAID, non-steroidal anti-inflammatory drug; PGI-I, patient global impression of improvement scale; QD, once per day; TA, triamcinolone acetonide; WOMAC, western Ontario and McMaster universities osteoarthritis index.

References

    1. Uchio Y, Enomoto H, Ishida M, et al. . Safety and efficacy of duloxetine in Japanese patients with chronic knee pain due to osteoarthritis: an open-label, long-term, phase III extension study. J Pain Res 2018;11:1391–403. 10.2147/JPR.S171395
    1. Uchio Y, Enomoto H, Alev L, et al. . A randomized, double-blind, placebo-controlled phase III trial of duloxetine in Japanese patients with knee pain due to osteoarthritis. J Pain Res 2018;11:809–21. 10.2147/JPR.S164128
    1. Bruyère O, Honvo G, Veronese N, et al. . An updated algorithm recommendation for the management of knee osteoarthritis from the European Society for clinical and economic aspects of osteoporosis, osteoarthritis and musculoskeletal diseases (ESCEO). Semin Arthritis Rheum 2019;49:337–50. 10.1016/j.semarthrit.2019.04.008
    1. Saccomanno MF, Donati F, Careri S, et al. . Efficacy of intra-articular hyaluronic acid injections and exercise-based rehabilitation programme, administered as isolated or integrated therapeutic regimens for the treatment of knee osteoarthritis. Knee Surg Sports Traumatol Arthrosc 2016;24:1686–94. 10.1007/s00167-015-3917-9
    1. Wang G, Bi L, Li X, et al. . Efficacy and safety of duloxetine in Chinese patients with chronic pain due to osteoarthritis: a randomized, double-blind, placebo-controlled study. Osteoarthritis Cartilage 2017;25:832–8. 10.1016/j.joca.2016.12.025
    1. Bjordal JM, Klovning A, Ljunggren AE, et al. . Short-Term efficacy of pharmacotherapeutic interventions in osteoarthritic knee pain: a meta-analysis of randomised placebo-controlled trials. Eur J Pain 2007;11:125–38. 10.1016/j.ejpain.2006.02.013
    1. Litwic A, Edwards MH, Dennison EM, et al. . Epidemiology and burden of osteoarthritis. Br Med Bull 2013;105:185–99. 10.1093/bmb/lds038
    1. Buckwalter JA, Saltzman C, Brown T. The impact of osteoarthritis: implications for research. Clin Orthop Relat Res 2004;427 Suppl:S6–15. 10.1097/01.blo.0000143938.30681.9d
    1. Murphy L, Schwartz TA, Helmick CG, et al. . Lifetime risk of symptomatic knee osteoarthritis. Arthritis Rheum 2008;59:1207–13. 10.1002/art.24021
    1. Jinks C, Jordan K, Croft P. Measuring the population impact of knee pain and disability with the Western Ontario and McMaster universities osteoarthritis index (WOMAC). Pain 2002;100:55–64. 10.1016/S0304-3959(02)00239-7
    1. Zhang W, Moskowitz RW, Nuki G, et al. . OARSI recommendations for the management of hip and knee osteoarthritis, part II: OARSI evidence-based, expert consensus guidelines. Osteoarthritis Cartilage 2008;16:137–62. 10.1016/j.joca.2007.12.013
    1. McAlindon TE, Bannuru RR, Sullivan MC, et al. . OARSI guidelines for the non-surgical management of knee osteoarthritis. Osteoarthritis and Cartilage 2014;22:363–88. 10.1016/j.joca.2014.01.003
    1. Chappell AS, Desaiah D, Liu-Seifert H, et al. . A double-blind, randomized, placebo-controlled study of the efficacy and safety of duloxetine for the treatment of chronic pain due to osteoarthritis of the knee. Pain Pract 2011;11:33–41. 10.1111/j.1533-2500.2010.00401.x
    1. Zhang W, Nuki G, Moskowitz RW, et al. . OARSI recommendations for the management of hip and knee osteoarthritis: Part III: changes in evidence following systematic cumulative update of research published through January 2009. Osteoarthritis Cartilage 2010;18:476–99. 10.1016/j.joca.2010.01.013
    1. Kon E, Filardo G, Drobnic M, et al. . Non-Surgical management of early knee osteoarthritis. Knee Surg Sports Traumatol Arthrosc 2012;20:436–49. 10.1007/s00167-011-1713-8
    1. Mora JC, Przkora R, Cruz-Almeida Y. Knee osteoarthritis: pathophysiology and current treatment modalities. J Pain Res 2018;11:2189–96. 10.2147/JPR.S154002
    1. Ariani A, Manara M, Fioravanti A, et al. . The Italian Society for rheumatology clinical practice guidelines for the diagnosis and management of knee, hip and hand osteoarthritis. Reumatismo 2019;71:5–21. 10.4081/reumatismo.2019.1188
    1. Altman RD, Manjoo A, Fierlinger A, et al. . The mechanism of action for hyaluronic acid treatment in the osteoarthritic knee: a systematic review. BMC Musculoskelet Disord 2015;16:321. 10.1186/s12891-015-0775-z
    1. Suntiparpluacha M, Tammachote N, Tammachote R. Triamcinolone acetonide reduces viability, induces oxidative stress, and alters gene expressions of human chondrocytes. Eur Rev Med Pharmacol Sci 2016;20:4985–92.
    1. Campos ALS, E Albuquerque RSP, da Silva EB, Campos A, E A R DSE, et al. . Viscosupplementation in patients with severe osteoarthritis of the knee: six month follow-up of a randomized, double-blind clinical trial. Int Orthop 2017;41:2273–80. 10.1007/s00264-017-3625-9
    1. Bannuru RR, Natov NS, Dasi UR, et al. . Therapeutic trajectory following intra-articular hyaluronic acid injection in knee osteoarthritis--meta-analysis. Osteoarthritis Cartilage 2011;19:611–9. 10.1016/j.joca.2010.09.014
    1. Bannuru RR, Osani MC, Vaysbrot EE, et al. . OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis. Osteoarthritis Cartilage 2019;27:1578–89. 10.1016/j.joca.2019.06.011
    1. Smith C, Patel R, Vannabouathong C, et al. . Combined intra-articular injection of corticosteroid and hyaluronic acid reduces pain compared to hyaluronic acid alone in the treatment of knee osteoarthritis. Knee Surg Sports Traumatol Arthrosc 2019;27:1974–83. 10.1007/s00167-018-5071-7
    1. Ertürk C, Altay MA, Altay N, et al. . Will a single periarticular lidocaine-corticosteroid injection improve the clinical efficacy of intraarticular hyaluronic acid treatment of symptomatic knee osteoarthritis? Knee Surg Sports Traumatol Arthrosc 2016;24:3653–60. 10.1007/s00167-014-3398-2
    1. McAlindon TE, LaValley MP, Harvey WF, et al. . Effect of intra-articular triamcinolone vs saline on knee cartilage volume and pain in patients with knee osteoarthritis: a randomized clinical trial. JAMA 2017;317:1967–75. 10.1001/jama.2017.5283
    1. Conaghan PG, Hunter DJ, Cohen SB, et al. . Effects of a single intra-articular injection of a microsphere formulation of triamcinolone acetonide on knee osteoarthritis pain: a double-blinded, randomized, placebo-controlled, multinational study. J Bone Joint Surg Am 2018;100:666–77. 10.2106/JBJS.17.00154
    1. McGarry JG, Daruwalla ZJ. The efficacy, accuracy and complications of corticosteroid injections of the knee joint. Knee Surg Sports Traumatol Arthrosc 2011;19:1649–54. 10.1007/s00167-010-1380-1
    1. Richards MM, Maxwell JS, Weng L, et al. . Intra-Articular treatment of knee osteoarthritis: from anti-inflammatories to products of regenerative medicine. Phys Sportsmed 2016;44:101–8. 10.1080/00913847.2016.1168272
    1. Enteshari-Moghaddam A, Azami A, Isazadehfar K, et al. . Efficacy of duloxetine and gabapentin in pain reduction in patients with knee osteoarthritis. Clin Rheumatol 2019;38:2873–80. 10.1007/s10067-019-04573-7
    1. Wong DT, Bymaster FP. Dual serotonin and noradrenaline uptake inhibitor class of antidepressants potential for greater efficacy or just hype? Prog Drug Res 2002;58:169–222. 10.1007/978-3-0348-8183-8_5
    1. Chappell AS, Ossanna MJ, Liu-Seifert H, et al. . Duloxetine, a centrally acting analgesic, in the treatment of patients with osteoarthritis knee pain: a 13-week, randomized, placebo-controlled trial. Pain 2009;146:253–60. 10.1016/j.pain.2009.06.024
    1. Wang G, Bi L, Li X, et al. . Efficacy and safety of duloxetine in Chinese patients with chronic pain due to osteoarthritis: a randomized, double-blind, placebo-controlled study. Osteoarthritis Cartilage 2017;25:832–8. 10.1016/j.joca.2016.12.025
    1. Altman R, Asch E, Bloch D, et al. . Development of criteria for the classification and reporting of osteoarthritis. classification of osteoarthritis of the knee. diagnostic and therapeutic criteria committee of the American rheumatism association. Arthritis Rheum 1986;29:1039–49. 10.1002/art.1780290816
    1. Garcia-Yu IA, Garcia-Ortiz L, Gómez-Marcos MA, et al. . Vascular and cognitive effects of cocoa-rich chocolate in postmenopausal women: a study protocol for a randomised clinical trial. BMJ Open 2018;8:e24095. 10.1136/bmjopen-2018-024095
    1. Cleeland CS, Ryan KM. Pain assessment: global use of the brief pain inventory. Ann Acad Med Singap 1994;23:129–38.
    1. Bellamy N, Buchanan WW, Goldsmith CH, et al. . Validation study of WOMAC: a health status instrument for measuring clinically important patient relevant outcomes to antirheumatic drug therapy in patients with osteoarthritis of the hip or knee. J Rheumatol 1988;15:1833–40.
    1. William G. ECDEU assessment manual for psychopharmacology. Washington, DC: US Department of Health, Education, and Welfare, 1976.
    1. Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand 1983;67:361–70. 10.1111/j.1600-0447.1983.tb09716.x
    1. Hansson L, Hedner T, Dahlöf B. Prospective randomized open blinded end-point (probe) study. A novel design for intervention trials. prospective randomized open blinded end-point. Blood Press 1992;1:113–9. 10.3109/08037059209077502
    1. Abou-Raya S, Abou-Raya A, Helmii M. Duloxetine for the management of pain in older adults with knee osteoarthritis: randomised placebo-controlled trial. Age Ageing 2012;41:646–52. 10.1093/ageing/afs072
    1. Kidd BL. Osteoarthritis and joint pain. Pain 2006;123:6–9. 10.1016/j.pain.2006.04.009
    1. Mease PJ, Hanna S, Frakes EP, et al. . Pain mechanisms in osteoarthritis: understanding the role of central pain and current approaches to its treatment. J Rheumatol 2011;38:1546–51. 10.3899/jrheum.100759
    1. Brunton S, Wang F, Edwards SB, et al. . Profile of adverse events with duloxetine treatment: a pooled analysis of placebo-controlled studies. Drug Saf 2010;33:393–407. 10.2165/11319200-000000000-00000
    1. Whitmyer VG, Dunner DL, Kornstein SG, et al. . A comparison of initial duloxetine dosing strategies in patients with major depressive disorder. J Clin Psychiatry 2007;68:1921–30. 10.4088/JCP.v68n1213
    1. Rizea-Savu S, Duna SN, Ghita A, et al. . The effect of food on the single-dose bioavailability and tolerability of the highest marketed strength of duloxetine. Clin Pharmacol Drug Dev 2019;00:1–8. 10.1002/cpdd.759
    1. Micca JL, Ruff D, Ahl J, et al. . Safety and efficacy of duloxetine treatment in older and younger patients with osteoarthritis knee pain: a post hoc, subgroup analysis of two randomized, placebo-controlled trials. BMC Musculoskelet Disord 2013;14:137. 10.1186/1471-2474-14-137

Source: PubMed

Спонсоры и соавторы

Заболевания

Медикаментозные вмешательства

Подписаться