Læknablaðið : fylgirit - 01.05.1978, Page 80

Medical School University of MULTICLINIC TRIAL OF
Massachutes SULINDAC IN HIP
OSTEOARTHRITIS
MK-231, also known as sulindac or clinoiel
is a new nonsteroidal antirheumatic drug that has
recently been evaluated in osteoarthritis of the
hip by 7 participating clinics. In animal testing,
sulindac has been found to have a spectrum of
anti-inflammatory activity similar to indomethacin.
It differs from indomethacin in that the basic
formula contains an indene structure rather than
the indole ring found in indomethacin.
The primary aims of the current study were
fourfold: (1) to compare the efficacy of suiindac
to that of placebo, (2) to establish the optimal
dose of sulindac, (3) to compare the efficacy
and tolerability of sulindac when given on a
q.i.d. versus a b.i.d. regimen, and (4) to obtain
short-term safety data.
Patients admitted to the study had to fulfill the
following diagnostic criteria: a history of hip
pain which was aggravated by motion and relieved
by rest; limitation of hip motion; and X-ray
evidence of joint space narrowing, osteophytes,
and sclerosis of the hip joint. Males and post-
menopausal women between the ages of 40 and
75 were eligible provided they had no coexisting
rheumatic disorder or significant gastrointestinal,
renal, hepatic, or cardiovascular disease.
Patients with malignancy, diabetes, tuberculosis,
oi hypersensitivity to indomethacin were also
exciuded, as were patients on systemic steroids
or anticoagulants. In addition, patients were not
to take any analgesics, tranquilizers, muscle re-
laxants, sleeping pills, or any type of cold
remedy during the trial.
Patients were randomly assigned to receive
sulindac b.i.d. , sulindac q.i.d., or placebo in
a double-blind manner. The dosage of sulindac
was 100 to 300 mg daily, being adjusted during
the trial according to the patient's needs and
acceptance of the test drug. Each patient
received identically-appearing capsules of sulindac
or placebo which were taken immediately after
breakfast, lunch, dinner, and following a light
snack at 9 PM.
Each patient was examined five times during
the study: At the time of selection for study,
when the previous antirheumatic drug was with-
drawn; when flare occurred and the test drug
was started; 3 to 7 days later for evaluation
and dosage adjustment if necessary; 3 to 7 days
later for another evaluation and dosage adjustment
if necessary; and finally, again in one week when
the final evaluation was performed. Therefore,
each patient who completed the trial received
medication for 2 to 3 weeks.
Patients assigned to sulindac b.i.d. were begun
on an initial dosage of 100 mg, a 50 mg capsule
after breakfast and another at 9 PM. They
received placebo after lunch and again after dinner.
At the first adjustment, 3 to 7 days later, the
dosage of sulindac could be raised to 200 mg
daily, 100 mg after breakfast and 100 mg at 9
PM. At the second adjustment, patients could
receive 300 mg daily, 150 mg after breakfast
and 150 mg after their night-time snack.
Patients on sulindac q.i.d. also received 100
mg daily initially, but took 25 mg capsules after
each daytime meal and at 9 PM. At the first
adjustment, if necessary, 200 mg daily was given;
at the second adjustment, 300 mg daily.
Patients assigned to placebo received identically
appearing capsules after eaeh of the four meals,
with a comparable increase in capsules similar
to that for sulindac at both the first and second
adjustment periods.
At each visit, a number of parameters were
measured, including 7 subjective and 8 objective
evaluations, as .well as the global response of
both patient and investigator. We also performed
a battery of laboratory studies and observed for
adverse reaction.
Laboratory studies done at each visit are shown
here. Hematology included hemoglobin, hema-
tocrit, white count and differential, platelets,
prothrombin time, partial thromboplastin, and
erythrocyte sedimentation rate. Chemistries
included alkaline phosphatase, total bilirubin,
SGOT, creatinine, uric acid, BUN, and a serum
salicylate level.
There were 7 subjective evaluations: hip pain
on weight bearing; and again on passive motion,
duration of stiffness (gelling); night pain; diffi-
culty in a specific functional activity; the patient's
opinion as to the overall degree of disease activity;
and the patients's assessment of global response.
There were 8 objective evaluations: degree of
flexion deformity; limitation of motion with
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