Phlogenzym in the treatment of a monoarticular painful gonarthritis
Efficacy and tolerance

Herrera E.G.

Hospital Aragon Avenida 506 entre Calle 521 y 519, Unidad San Juan de Aragon, Delegacion Gustavo A. Madero, Mexico D.F., C.P. 0792

Randomised 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.