Patient Preference for Placebo, Acetaminophen (paracetamol) or Celecoxib Efficacy Studies (PACES): two randomised, double blind, placebo controlled, crossover clinical trials in patients with knee or hip osteoarthritis

Abstract

Background: Acetaminophen (paracetamol) is recommended as the initial pharmacological treatment for knee or hip osteoarthritis. However, survey and clinical trial data indicate greater efficacy for non-steroidal anti-inflammatory drugs and cyclo-oxygenase-2 specific inhibitors.

Design: Two randomised, double blind, placebo controlled, crossover multicentre clinical trials, Patient Preference for Placebo, Acetaminophen or Celecoxib Efficacy Studies (PACES).

Patients: Osteoarthritis of knee or hip.

Intervention: "Wash out" of treatment; randomisation; 6 weeks of celecoxib 200 mg/day, acetaminophen 1000 mg four times a day, or placebo; second "wash out;" crossover to 6 weeks of second treatment.

Measurements: Western Ontario McMaster Osteoarthritis Index (WOMAC), visual analogue pain scale, patient preference between two treatments.

Results: Celecoxib was more efficacious than acetaminophen in both periods in both studies; WOMAC and pain scale scores differed at p<0.05 in period II and both periods combined of PACES-a and in periods I and II and both periods combined in PACES-b, but not in period I of PACES-a. Acetaminophen was more efficacious than placebo, generally p<0.05 in PACES-b, and >0.05 in PACES-a. Patient preferences were 53% celecoxib v 24% acetaminophen in PACES-a (p<0.001) and 50% v 32% in PACES-b (p = 0.009); 37% acetaminophen v 28% placebo in PACES-a (p = 0.340) and 48% v 24% in PACES-b (p = 0.007). No clinically or statistically significant differences were seen in adverse events or tolerability among the three treatment groups.

Conclusions: Greater efficacy was seen for celecoxib v acetaminophen v placebo, while adverse events and tolerability were similar. Variation in results and statistical significance in the two different trials are of interest.

Figure 1

Summary of protocol of PACES—double blind, double dummy, clinical trials. Each patient received a drug and a placebo or two placebos in each period.

Figure 2

Change in scores for WOMAC (A and B) and pain visual analogue scale scores on the MDHAQ (C and D) of patients who received 6 weeks' treatment with celecoxib, acetaminophen, or placebo, after a 1 week washout period, in PACES-a and PACES-b.

Figure 3

Patient Preference for Placebo, Acetaminophen or Celecoxib in PACES-a (A) and PACES-b (B). Each patient took two of the three treatments for 6 weeks each. At the final visit, the patient questionnaire asked: "Please compare control of your arthritis during the first and second study periods," with five response options, "much better during first study period," "better during first study period," "no difference in first and second study periods," "better during second study period," "much better during second study period." Patients who responded "much better" or "better" in either period were merged in these analyses.