title: A randomised controlled trial of ibuprofen, paracetamol or a combination tablet of ibuprofen/paracetamol in community-derived people with knee pain.
abstract: OBJECTIVE
  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.
authors.affiliation: Arthritis Research UK Pain Centre, Academic Rheumatology, Nottingham City Hospital, UK. michael.doherty@nottingham.ac.uk
authors.forename: Michael
authors.initials: M
authors.lastname: Doherty
authors.forename: Chris
authors.initials: C
authors.lastname: Hawkey
authors.forename: Michael
authors.initials: M
authors.lastname: Goulder
authors.forename: Iain
authors.initials: I
authors.lastname: Gibb
authors.forename: Nicola
authors.initials: N
authors.lastname: Hill
authors.forename: Sue
authors.initials: S
authors.lastname: Aspley
authors.forename: Sandie
authors.initials: S
authors.lastname: Reader
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D002908:Chronic Disease; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005260:Female; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D007052:Ibuprofen / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D007719:Knee Joint / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D004366:Nonprescription Drugs / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D020370:Osteoarthritis, Knee / Q000188:drug therapy; D010146:Pain / Q000188:drug therapy*; D010147:Pain Measurement / Q000379:methods; D016896:Treatment Outcome
chemical_list: D018712:Analgesics, Non-Narcotic; D004338:Drug Combinations; D006454:Hemoglobins; D004366:Nonprescription Drugs; D000082:Acetaminophen; D007052:Ibuprofen