PMID- 19393841 OWN - NLM STAT- MEDLINE DCOM- 20090611 LR - 20220311 IS - 0149-2918 (Print) IS - 0149-2918 (Linking) VI - 31 IP - 3 DP - 2009 Mar TI - Efficacy and safety of low-dose transdermal buprenorphine patches (5, 10, and 20 microg/h) versus prolonged-release tramadol tablets (75, 100, 150, and 200 mg) in patients with chronic osteoarthritis pain: a 12-week, randomized, open-label, controlled, parallel-group noninferiority study. PG - 503-13 LID - 10.1016/j.clinthera.2009.03.001 [doi] AB - OBJECTIVE: This study compared the efficacy and safety of low-dose 7-day buprenorphine patches and prolonged-release tramadol tablets in patients with chronic, moderate to severe osteoarthritis (OA) pain of the hip and/or knee. METHODS: Eligible patients were adults with a clinical and radiologic diagnosis of OA of the hip and/or knee and moderate to severe pain, as confirmed by a mean Box Scale 11 (BS-11) score >or=4 while using paracetamol 4000 mg/d for pain during the screening week. Patients were randomized in a 1:1 ratio to receive either low-dose 7-day buprenorphine patches (patch strengths of 5, 10, and 20 microg/h, with a maximum dosage of 20 microg/h) or twice-daily prolonged-release tramadol tablets (tablet strengths of 75, 100, 150, and 200 mg, with a maximum dosage of 400 mg/d) over a 12-week open-label treatment period. Supplementary paracetamol was available as rescue medication throughout the study. The primary end point was the difference in BS-11 scores from baseline to the completion of treatment. Noninferiority was assumed if the treatment difference on the BS-11 scale was -1.5 boxes, indicating a clinically meaningful result. Secondary efficacy variables were rescue medication use, sleep disturbance and quality of sleep, and patients' and investigators' global assessments of pain relief. In addition, patient preference was assessed at the completion visit by asking patients whether, given equal pain relief, they would prefer basic treatment for OA pain with a patch applied once weekly or a tablet taken twice daily. Exploratory variables included investigators' assessments of patients' pain, stiffness, and ability to perform daily activities (Western Ontario and McMaster Universities Osteoarthritis Index); patients' quality of life (EuroQol EQ-5D health states index and EuroQol visual analog scale); and abuse and diversion of study drug. RESULTS: One hundred thirty-four patients (69 receiving 7-day buprenorphine patches and 65 receiving tramadol tablets) were randomized and received >or=1 dose of study medication. A respective 98.6% and 100% of the 2 treatment groups were white, with mean (SD) ages of 64.4 (11.1) and 64.2 (9.3) years. Both treatments were associated with a clinically meaningful reduction in pain from baseline to study completion. The least squares mean change from baseline in BS-11 scores in the 7-day buprenorphine patch and tramadol tablet groups was -2.26 (95% CI, -2.76 to -1.76) and -2.09 (95% CI, -2.61 to -1.58). The efficacy of 7-day buprenorphine patches was noninferior to that of prolonged-release tramadol tablets. The incidence of adverse events (AEs) was comparable in the 2 treatment groups: 226 AEs were reported in 61 patients (88.4%) in the 7-day buprenorphine patch group, and 152 AEs were reported in 51 patients (78.5%) in the tramadol group. Ten patients (14.5%) in the 7-day buprenorphine patch group and 19 (29.2%) in the tramadol tablet group withdrew from the study due to AEs. The most common AEs in the 7-day buprenorphine patch group were nausea (30.4%), constipation (18.8%), and dizziness (15.9%); the most common AEs in the tramadol tablet group were nausea (24.6%), fatigue (18.5%), and pain (12.3%). Most patients (47/67 [70.1%] in the 7-day buprenorphine patch group and 43/61 [70.5%] in the tramadol tablet group) reported that they would prefer a 7-day patch to a twice-daily tablet for future pain treatment. CONCLUSIONS: In these patients with chronic, moderate to severe OA pain of the hip and/or knee, 7-day low-dose buprenorphine patches were an effective and well-tolerated analgesic. The buprenorphine patches were noninferior to prolonged-release tramadol tablets. European Union Drug Regulating Authorities Clinical Trials number: 2006-003233-32. FAU - Karlsson, Mats AU - Karlsson M AD - Smartkliniken Sankt Olof, Falkoping, Sweden. mats@smartkliniken.se FAU - Berggren, Anna-Carin AU - Berggren AC LA - eng PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't PL - United States TA - Clin Ther JT - Clinical therapeutics JID - 7706726 RN - 0 (Analgesics, Non-Narcotic) RN - 0 (Analgesics, Opioid) RN - 0 (Delayed-Action Preparations) RN - 0 (Tablets) RN - 362O9ITL9D (Acetaminophen) RN - 39J1LGJ30J (Tramadol) RN - 40D3SCR4GZ (Buprenorphine) SB - IM MH - Acetaminophen/therapeutic use MH - Administration, Cutaneous MH - Administration, Oral MH - Adult MH - Aged MH - Aged, 80 and over MH - Analgesics, Non-Narcotic/therapeutic use MH - Analgesics, Opioid/*administration & dosage/adverse effects MH - Buprenorphine/*administration & dosage/adverse effects MH - Chronic Disease MH - Delayed-Action Preparations MH - Drug Administration Schedule MH - Humans MH - Middle Aged MH - Osteoarthritis, Hip/complications/diagnostic imaging/*drug therapy MH - Osteoarthritis, Knee/complications/diagnostic imaging/*drug therapy MH - Pain/etiology/*prevention & control MH - Pain Measurement MH - Patient Satisfaction MH - Radiography MH - Sleep/drug effects MH - Sweden MH - Tablets MH - Time Factors MH - Tramadol/*administration & dosage/adverse effects MH - Treatment Outcome EDAT- 2009/04/28 09:00 MHDA- 2009/06/12 09:00 CRDT- 2009/04/28 09:00 PHST- 2009/01/22 00:00 [accepted] PHST- 2009/04/28 09:00 [entrez] PHST- 2009/04/28 09:00 [pubmed] PHST- 2009/06/12 09:00 [medline] AID - S0149-2918(09)00067-8 [pii] AID - 10.1016/j.clinthera.2009.03.001 [doi] PST - ppublish SO - Clin Ther. 2009 Mar;31(3):503-13. doi: 10.1016/j.clinthera.2009.03.001.