J Int Med Res (1979) 7, 272
A Comparative Clinical Trial of Diftunisal and Ibuprofen in the Control of Pain in Osteoarthritis J G M Keet, MD, PhD, Department of Orthopaedic Surgery, Hospital 'de Weezenlanden', Zwolle, The Netherlands. A randomized double-blind study in ambulatory patients with osteoarthritis of hip and/or knee was conducted, comparing the efficacy and sq{ety of diflunisal 500 mg daily with ibuprofen 1200 mg daily, over a period of 8 weeks. Thirty-fivepatients participated in the study. The results revealed no significant differences between the treatment groups with regard to the efficacyparameters.
Introduction Diftunisal is an analgesic agent, a derivative of salicylic acid with a potency 2-16 times that of ASA in various animal models. Despite the greater potency, diftunisal produced less gastro-intestinal irritation in animal and human studies than ASA (Tait et al 1977, Caruso et aI1977). Diftunisal is well absorbed following oral administration and achieves peak plasma concentrations in 2-3 hours. The initial plasma half-life of diftunisal appeared to be 10-12 hours for the 500 mg dose (versus 2-3 hours for ASA) (Steelman, Breault & Tocco 1975). Ibuprofen is an anti-inflammatory drug with analgesic properties, which is commonly used at a dosage of 400 mg tid. in various rheumatic disorders. The purpose of this study was to compare the efficacy and safety of diftunisal and ibuprofen in patients with osteoarthritis of hip and/or knee. Material and Methods Patient selection Thirty-five ambulatory patients participated in the study. There were seventeen patients in the 0300-0605/79/040272-05 $02·00
diflunisal group and eighteen patients in the ibuprofen group. Eleven male and twenty-four female patients, ranging in age from 30 to 71 years, took part in the study. The demographic and diagnostic characteristics are listed in Table 1: no statistically significant difference was found between the treatment groups. Patients participating in this study had a definite diagnosis of osteoarthritis. Patients in any of the following categories were excluded from the study: evidence of severe consolidated forms of osteoarthritis, pregnancy or a practical possibility of pregnancy, nursing mothers, hypersensitivity to salicylates or to ibuprofen, current treatment with systemic corticosteroids or anticoagulants, active peptic ulcer or gastrointestinal haemorrhage, a clinical history of significant liver or kidney disease, a clinical history of haemopoietic disorders. Concomitant use of other analgesics, antiinftammatories or local injection therapies was not permitted during the study. The use of antacids was to be avoided. If antacids were indicated, only drugs without aluminium hydroxide were to be chosen.
@Cambridge Medical Publications Limited
273
JGM Keel
differential, serum creatinine, total bilirubin, SGOT and alkaline phosphatase. The different parameters and the times of evaluation are shown in Table 2.
Table 1 Demographic and diagnostic characteristics
Diflunisal
Ibuprofen
6 II
5 13
Mean age
53·3 yrs
51· 7 yrs
Mean body-weight
77·5 kg
72·3 kg
6·0 yrs
4·5 yrs
Male Female
Mean duration of OA Joint:
Hip Knee
9 8
10 8
Physiotherapy, initiated prior to the study, should be continued but such therapy was not to be initiated during the trial. All test medication was to be taken with meals or with a glass of milk.
Procedure
Table 2 -1
0
2
4
8
Weight-bearing pain
X
X
X
X
X
Reduction functional activity
X
X
X
X
X
Inactivity stiffness
X
X
X
X
X
Night pain
X
X
X
X
X
X
X
X
X
X
X
Week
Patient's Assessment of therapy Investigator's Laboratory tests
X
X
Due to the different dosage forms and treatment regimens, a double-dummy technique of drug administration was used to maintain the double-blind nature of the trial. Table 3 summarizes the test medication taken daily by patients in each treatment group.
During the initial visit, patients were assessed by the investigator with regard to the admission criteria. Patients discontinued any current drug therapy for osteoarthritis and commenced a placebo wash-out period (one tablet t.i.d.). Patients returned after one week, or sooner Table 3 if their condition worsened. At the end of the wash-out period, patients who complained of Treatment weight-bearing pain and of a reduction in a group Morning Noon Evening functional activity were randomly allocated to Diflunisal I x0 2 x IP I x0 either the diflunisal group or the ibuprofen 2 x IP 2 x IP group. Patients were seen at the start of Ibuprofen 2 xI I x DP I x DP 2 xI 2 :
A Comparative Clinical Trial of Diftunisal and Ibuprofen in the Control of Pain in Osteoarthritis J G M Keet, MD, PhD, Department of Orthopaedic Surgery, Hospital 'de Weezenlanden', Zwolle, The Netherlands. A randomized double-blind study in ambulatory patients with osteoarthritis of hip and/or knee was conducted, comparing the efficacy and sq{ety of diflunisal 500 mg daily with ibuprofen 1200 mg daily, over a period of 8 weeks. Thirty-fivepatients participated in the study. The results revealed no significant differences between the treatment groups with regard to the efficacyparameters.
Introduction Diftunisal is an analgesic agent, a derivative of salicylic acid with a potency 2-16 times that of ASA in various animal models. Despite the greater potency, diftunisal produced less gastro-intestinal irritation in animal and human studies than ASA (Tait et al 1977, Caruso et aI1977). Diftunisal is well absorbed following oral administration and achieves peak plasma concentrations in 2-3 hours. The initial plasma half-life of diftunisal appeared to be 10-12 hours for the 500 mg dose (versus 2-3 hours for ASA) (Steelman, Breault & Tocco 1975). Ibuprofen is an anti-inflammatory drug with analgesic properties, which is commonly used at a dosage of 400 mg tid. in various rheumatic disorders. The purpose of this study was to compare the efficacy and safety of diftunisal and ibuprofen in patients with osteoarthritis of hip and/or knee. Material and Methods Patient selection Thirty-five ambulatory patients participated in the study. There were seventeen patients in the 0300-0605/79/040272-05 $02·00
diflunisal group and eighteen patients in the ibuprofen group. Eleven male and twenty-four female patients, ranging in age from 30 to 71 years, took part in the study. The demographic and diagnostic characteristics are listed in Table 1: no statistically significant difference was found between the treatment groups. Patients participating in this study had a definite diagnosis of osteoarthritis. Patients in any of the following categories were excluded from the study: evidence of severe consolidated forms of osteoarthritis, pregnancy or a practical possibility of pregnancy, nursing mothers, hypersensitivity to salicylates or to ibuprofen, current treatment with systemic corticosteroids or anticoagulants, active peptic ulcer or gastrointestinal haemorrhage, a clinical history of significant liver or kidney disease, a clinical history of haemopoietic disorders. Concomitant use of other analgesics, antiinftammatories or local injection therapies was not permitted during the study. The use of antacids was to be avoided. If antacids were indicated, only drugs without aluminium hydroxide were to be chosen.
@Cambridge Medical Publications Limited
273
JGM Keel
differential, serum creatinine, total bilirubin, SGOT and alkaline phosphatase. The different parameters and the times of evaluation are shown in Table 2.
Table 1 Demographic and diagnostic characteristics
Diflunisal
Ibuprofen
6 II
5 13
Mean age
53·3 yrs
51· 7 yrs
Mean body-weight
77·5 kg
72·3 kg
6·0 yrs
4·5 yrs
Male Female
Mean duration of OA Joint:
Hip Knee
9 8
10 8
Physiotherapy, initiated prior to the study, should be continued but such therapy was not to be initiated during the trial. All test medication was to be taken with meals or with a glass of milk.
Procedure
Table 2 -1
0
2
4
8
Weight-bearing pain
X
X
X
X
X
Reduction functional activity
X
X
X
X
X
Inactivity stiffness
X
X
X
X
X
Night pain
X
X
X
X
X
X
X
X
X
X
X
Week
Patient's Assessment of therapy Investigator's Laboratory tests
X
X
Due to the different dosage forms and treatment regimens, a double-dummy technique of drug administration was used to maintain the double-blind nature of the trial. Table 3 summarizes the test medication taken daily by patients in each treatment group.
During the initial visit, patients were assessed by the investigator with regard to the admission criteria. Patients discontinued any current drug therapy for osteoarthritis and commenced a placebo wash-out period (one tablet t.i.d.). Patients returned after one week, or sooner Table 3 if their condition worsened. At the end of the wash-out period, patients who complained of Treatment weight-bearing pain and of a reduction in a group Morning Noon Evening functional activity were randomly allocated to Diflunisal I x0 2 x IP I x0 either the diflunisal group or the ibuprofen 2 x IP 2 x IP group. Patients were seen at the start of Ibuprofen 2 xI I x DP I x DP 2 xI 2 :
