Evaluation of Serratia Peptidase in Acute or Chronic Inflammation of Otorhinolaryngology Pathology: a Multicentre, Double-blind, Randomized Trial versus Placebo

A. Mazzone1, M. Catalan2, M. Costanzo3, A. Drusian4, A. Mandol5, S. Russo6, E. Guarini7 and G. Vesperini8

1Institute of Clinical Otorhinolaryngology, University of Naples, Naples, Italy;
2Ear, Nose and Throat Department, 'Gradenigo' Hospital, Turin, Italy;
3Ear, Nose and Throat Department, 'Villa Sofia' Hospital, Palermo, Italy;
4Ear Nose and Throat Department, Treviso Regional Hospital, Treviso, Italy;
5Ear, Nose and Throat Department, 'E. Fornaroli' Hospital, Magenta, Italy;
6Ear, Nose and Throat Department, Lucca Hospital, Lucca, Italy;
7Ear, Nose and Throat Department, Civil Hospital, Lecce, Italy;
8Ear, Nose and Throat Department, 'Madonna del Soccorso' Hospital, San Benedetto del Tronto, Italy

The efficacy and tolerability of Serratia peptidase were evaluated in a multi-centre, double-blind, placebo-controlled study of 193 subjects suffering from acute or chronic ear, nose or throat disorders. Treatment lasted 7 - 8 days, with the drug or placebo being administered at a rate of two tablets three times a day. After 3-4 days' treatment, significant symptom regression was observed in peptidase-treated patients. There was also a significant reduction in symptoms after 7 -8 days for patients in both treatment groups but the response was more marked in those patients receiving the active drug. Statistical comparison between the two groups confirmed the greater efficacy and rapid action of the peptidase against all the symptoms examined at both stages. Tolerance was found to be very good and similar for both groups. It is concluded that Serratia peptidase has anti-inflapimatory, anti-edemic and fibrinolytic activity and acts rapidly on localized inflammation.

Received for publication 2 January 1990; accepted 16 January 1990.

Address for correspondence: A. Mazzone, MD, Institute of Clinical Otorhinolaryngology, University of Naples, Via Pansini 5, 80131 Naples, Italy.

INTRODUCTION

The use of enzymes with fibrinolytic, I proteolytic and anti-edemic activities has gained increasing support in recent years for the treatment of inflammatory ear, nose and throat (ENT) conditions1. Included among these enzymes is the Serratia peptidase (Danzen® ), a protease obtained from non-pathogenic enterobacteria of the genus Serratia. This proteolytic enzyme, which is available in tablet form to enable it to be absorbed from the intestinal lumen, has been shown lo induce intense fibrinolytic. anti-inflammatory, and anti-edemic activity in a number of tissues and results suggest that its anti-inflammatory activity may be of particular use for the treatment of localized or 'closed' forms of inflammation, such as those frequently found in ENT pathologies.' ^ Another important feature of Serratia peptidase is its effect on pain, the enzyme acting by inhibiting the release of pain-inducing amines, such as bradykinin, from inflammed tissue.1.7

This peptidase induces fragmentation offibrinose aggregates and reduces the viscosity of exudates,"^ thus facilitating the drainage of these products of the inflammatory response and thereby promoting the tissue repair process, and clinical trials have confirmed that the use of Serratia peptidase resulted in fast resolution of the inflammatory process." ~ '° The aim of the present placebo-controlled multicentre study was to evaluate the efficacy and tolerability of the Serratia peptidase in the treatment of ENT inflammatory conditions.

PATIENTS AND METHODS

Patients, who were recruited from ENT clinics throughout Italy, were all suffering from inherent acute or chronic inflammatory conditions. Any patients with serious concomitant conditions, such as severe renal and/or hepatic impairments, or who required additional drugs were excluded from the tnal, as this could interfere with evaluation of the parameters under examination, and the use of steroids, non-steroidal anti-inflammatory drugs and/or anti-inflammatory/analgesic agents was prohibited. Antibiotics were permitted when deemed necessary.

Treatment

Indistinguishable tablets containing 5 mg Serratia peptidase or a placebo were provided in blister packs and patients were randomly assigned to receive two tablets of either drug, which they were instructed to take three times daily after meals for 7 -8 days.

Evaluation of treatment
Clinical signs and symptoms were assessed on days 0, 3-4 and 7-8 of treatment on a scale of O-3 (0, absence of the symptoms: 3, maximum severity). Clinical parameters recorded were as follows: pain; quantity of secretion; difficulty in swallowing; nasal obstruction; anosmia; and body temperature. The appearance of the secretion was also recorded on a scale ofO-3 (0, normal; I, mucoid; 2, mucopurulent: 3, purulent). All evaluations were performed by an ENT specialist unaware of the treatment given.

Evaluation of tolerability
Tolerability of Serralia peptidase was evaluated on the basis of the presence, absence or severity of side-effects, recorded on the patients' data-collecting forms.

Statistical analysis
All data were analysed by the most appropriate statistical tests (^-test and Student's f-test).

RESULTS

A total of 193 subjects (96 males, 97 females), aged between 12 and 77 years (mean ± SD 38 ± 15.7 years), with acute or chronic ENT pathologies were recruited to the trial. Of these 193 cases, 97 (43 males, 54 females; mean ± SD 37.3 ± 15.2 years) were placed in group A and 96 (53)