Objectives To compare the efficacy and safety of single versus combination non-prescription oral analgesics in community-derived people aged 40 years and older with chronic knee pain.
Methods A randomised, double-blind, four-arm, parallel-group, active controlled trial investigating short-term (day 10) and long-term (week 13) benefits and side-effects of four regimens, each taken three times a day: ibuprofen (400 mg); paracetamol (1000 mg); one fixed-dose combination tablet (ibuprofen 200 mg/paracetamol 500 mg); two fixed-dose combination tablets (ibuprofen 400 mg/paracetamol 1000 mg).
Results There were 892 participants (mean age 60.6, range 40–84 years); 63% had radiographic knee osteoarthritis and 85% fulfilled American College of Rheumatology criteria for osteoarthritis. At day 10, two combination tablets were superior to paracetamol (p<0.01) for pain relief (determined by mean change from baseline in WOMAC pain; n=786). At 13 weeks, significantly more participants taking one or two combination tablets rated their treatment as excellent/good compared with paracetamol (p=0.015, p=0.0002, respectively; n=615). The frequency of adverse events was comparable between groups. However, by 13 weeks, decreases in haemoglobin (≥1 g/dl) were observed in some participants in all groups. Twice as many participants taking two combination tablets had this decrease compared with those on monotherapy (p<0.001; paracetamol, 20.3%; ibuprofen, 19.6%; one or two combination tablets, 24.1%, 38.4%, respectively).
Conclusions Ibuprofen/paracetamol combination analgesia, at non-prescription doses, confers modest short-term benefits for knee pain/osteoarthritis. However, in this population, paracetamol 3 g/day may cause similar degrees of blood loss as ibuprofen 1200 mg/day, and the combination of the two appears to be additive.
Study no ISRCTN77199439
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Funding This trial was sponsored by Reckitt Benckiser Healthcare International Ltd; study no: ISRCTN77199439. Editorial assistance was provided by Debra Scates, Elements Communications Ltd, supported by Reckitt Benckiser Healthcare International Ltd.
Competing interests MD received no personal financial reimbursement for the study, but has received honoraria for attending two advisory boards for Reckitt Benckiser. CH has received honoraria for attending advisory boards for Reckitt Benckiser. SA is currently an employee of Reckitt Benckiser and IG and SR were previously employed by Reckitt Benckiser and received salary and travel expenses. MG and NH have no conflict of interest relating to this publication.
Patient consent Obtained.
Ethics approval This study was conducted with the approval of the Southampton and South West Hampshire Research Ethics Committee (A) of the NHS National Research Ethics Service.
Provenance and peer review Not commissioned; externally peer reviewed.