Effectiveness and cost-effectiveness of duloxetine added to usual care for patients with chronic pain due to hip or knee osteoarthritis: Protocol of a pragmatic open-label cluster randomised trial (the DUO trial)

__Introduction__ Osteoarthritis (OA) is a highly prevalent painful condition of the musculoskeletal system. The effectiveness of current analgesic options has proven to be limited and improved analgesic treatment is needed. Several randomised placebo-controlled trials have now demonstrated the efficacy of duloxetine, an antidepressant with a centrally acting effect, in the treatment of OA pain. The aim of the current study is to investigate if duloxetine is effective and cost-effective as a third-choice analgesic added to usual care for treating chronic pain compared with usual care alone in general practice. __Methods and analysis__ A pragmatic open, cluster randomised trial is conducted. Patients with pain due to hip or knee OA on most days of the past 3 months with insufficient benefit of non-steroidal anti-inflammatory drugs or contraindications or intolerable side effects are included. General practices are randomised to either (1) duloxetine and usual care or (2) usual care only. Primary outcome is pain at 3 months measured on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale. Secondary outcomes at 3 months and 1 year are pain (WOMAC, at 1 year), function (WOMAC), adverse reactions, quality of life and modification of the response to treatment by the presence of centrally sensitised pain (modified PainDETECT). At 1 year, medical and productivity costs will be assessed. Analyses will be performed following the intention-to-treat principle taking the cluster design into account. __Ethics and dissemination__ The study is approved by the local Medical Ethics Committee (2015-293). Results will be published in a scientific peer-reviewed journal and will be communicated at conferences. _Trial registration number_ Dutch Trial Registry(ntr4798); Pre-results