1. Ann Rheum Dis. 2011 Sep;70(9):1534-41. doi: 10.1136/ard.2011.154047.

A randomised controlled trial of ibuprofen, paracetamol or a combination tablet
of ibuprofen/paracetamol in community-derived people with knee pain.

Doherty M(1), Hawkey C, Goulder M, Gibb I, Hill N, Aspley S, Reader S.

Author information: 
(1)Arthritis Research UK Pain Centre, Academic Rheumatology, Nottingham City
Hospital, UK. michael.doherty@nottingham.ac.uk

Comment in
    Ann Rheum Dis. 2011 Sep;70(9):1521-2.
    Ann Intern Med. 2012 Mar 20;156(6):JC3-12.
    Orthopade. 2012 Nov;41(11):923-4.

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.

DOI: 10.1136/ard.2011.154047 
PMID: 21804100  [Indexed for MEDLINE]