Phlogenzym in the treatment of a monoarticular painful gonarthritis.
Efficacy and tolerance. (MU-696416)
Herrera E.G. Phlogenzym in the treatment of a monoarticular
painful gonarthritis. Efficacy and tolerance. Hospital Aragon
Avenida 506 entre Calle 521 y 519, Unidad San Juan de Aragon,
Delegacion Gustavo A. Madero, Mexico D.F., C.P. 0792.
Randomized double-blind study
with parallel groups vs. diclofenac.
Study Period: January
1997 - May 1997. Study No.:
MU-696 416
Summary
A double-blind clinical study was performed to prove efficacy and
tolerance of Phlogenzym® for equivalence with the
non-steroidal anti-inflammatory drug diclofenac in monoarticular
gonarthritis.
60 patients were planned, 59 patients with monoarticular
gonarthritis were included and randomised into two groups: 30
patients received the enzyme preparation Phlogenzym®
(enzyme group), and 29 patients diclofenac (diclofenac group). The
data of all patients was evaluable.
The principal investigator was Ernesto Garcia Herrera, M.D.,
Hospital Aragon, Avenida 506 entre Calle 521 y 519, Unidad San Juan
de Aragon, Delegacion Gustavo A. Madero, Mexico D.F, C.P. 07920.
At baseline the patients were comparable with regard to age,
sex, weight, height, and symptoms (p > 0.05, Wilcoxon-Mann-Whitney-U-test).
As main endpoints for statistical evaluation the Lequesne
index and the sum score of the self-judgement (rest pain, pain on
movement, restricted movement assessed by the patients using a
"visual analog scale" [Huskisson score]) at of therapy were defined.
As secondary criteria the single self-judgements by the
patients, the result of the therapy, the motility of the knee
without pain, the circumference (cm) of the knee and the global
judgements of efficacy by the physician and by the patients were
evaluated descriptively.
During monitoring visits it was noted that about 50% of the
patients did not meet the inclusion criterion "Lequesne index at
baseline > 10.0". Nevertheless, it was decided to complete the study
in the foregiven period of time. The severity of the disease was
therefore lower than estimated; consequently, then the precalculated
number of patients was too low for statistical proof of equivalence.
The main endpoint "Lequesne index at end of therapy" was
equivalent in both groups: the Mann-Whitney statistics yielded a
value of 0.4592 with a lower bound of the 95% confidence interval of
0.3387. As this value is below 0.44, the equivalence could not be
proven statistically. The large range of the confidence interval
verifies that the missed significance is due to the low number of
patients.
The second main endpoint, the sum score of the symptoms,
showed similar results: the groups were equivalent, but without
statistical significance. The Mann-Whitney estimator was 0.5287,
with a lower bound of 0.4080, again below the limit (0.44) for
statistically proven equivalence.
The efficacy of the drug was judged in the enzyme group by the
physician as 2.2 ("good") and by the patients as 2.3 ("good" to
"moderate"). In the diclofenac group the physician judged the
efficacy of the drug as 2.0 ("good") and the patients as 2.1
("good"). The tolerance of the drugs was judged in the enzyme group
and in the diclofenac group by the physician and by the patients as
1.6 ("very good" to "good").
Adverse events were documented in one patient in the enzyme group (gastralgia,
nausea, vomiting, headache), and in two patients in the diclofenac
group (gastralgia, nausea, vomiting, flatulence, diarrhea). They
started after 10 days in the enzyme group and after 5.0 days in the
diclofenac group. The duration was 19 days in the enzyme group and
on average 13.5 days in the diclofenac group. They were judged in
the enzyme and in the diclofenac group as "moderate". They were in
all patients without sequelae.
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