A controlled multicenter pediatric study in the treatment of acute respiratory tract diseases with the aid of a new specific compound, erdosteine (IPSE, Italian Pediatric Study Erdosteine)

INTRODUCTION Erdosteine is an original drug which has been suggested as secretolytic compound and promoter of respiratory ventilation in the treatment of acute and chronic respiratory diseases. Moreover, the drug possesses also scavenging, antioxidant, and bacterial anti-adhesivity properties. From a clinical point of view the best results have been obtained by combined treatment with an antibiotic agent of useful spectrum activity. Aim of the present study was to evaluate the improvement induced in the risk/benefit ratio by erdosteine on the broad-spectrum antibiotic (ampicillin) in the treatment of acute lower respiratory tract diseases in the pediatric field. MATERIAL AND METHODS A controlled multicenter double-blind parallel group trial was planned comparing erdosteine, supplied as syrup 3.5% or as sachets 225 mg, versus the relevant placebo. The tested compounds were administered in association with ampicillin. Two-hundred (n = 200) subjects entered the trial, randomly selected among patients monitored by the different centers, and were assigned to one of the treatments under evaluation, i.e. active compound or placebo with the aim to constitute two comparative homogeneous groups of 100 subjects each. Subsequently each group was again divided according to age in two equivalent subgroups of 50 patients each and treated with the syrup 3.5% (age from 2 to 4 years) or the sachet form (age from 5 to 10 years). The treatments administered in the two comparison groups were erdosteine (syrup 3.5% and 225 mg sachets) or the relevant placebo. The erdosteine posologies were adapted according to age. The lower dosage of the 5-10 years range in comparison with the 2-4 years range was established on the base of bioavailability characteristics of the two pharmaceutical forms. In all groups ampicillin was administered at the dosage of 100 mg/kg/day, according to a b.i.d. time schedule. The primary efficacy criterion was the cough score evaluated in a subjective way and expressed with the following scores: 1 = absent; 2 = mild; 3 = moderate; 4 = severe. The secondary efficacy end-points were: body temperature (expressed in degrees C); the polypnea, ronchi and rales estimation with a rating scale similar to that previously mentioned. These parameters were determined before starting of the treatment (VO); at the 3rd +/- 1 (V1) and at the 7th +/- 2 (V2) day of treatment. The body temperature was measured orally in the morning at awakening time with a mercury thermometer. Obtained data expressed in Celsius degrees are recorded by the investigator in the patient file during control visits. The safety of adopted treatments was evaluated with two different approaches. The clinical part was determined with the adverse drug reactions (ADRs) estimate. The biological safety was estimated at admission day (day 0) and at the final visit by means of a sophisticated statistical approach. RESULTS The final results were the following: Erdosteine syrup 3.5%: concerning cough (primary end-point) in the group of patients (n = 50) treated with erdosteine it has been possible to point out a reduction of 23.8% at V1, i.e. after 3+/-1 days, and of 59.8% at V2, i.e. after 7+/-2 days. In the group of patients treated with placebo (n = 50) the reduction has been of 20.1% at V1 and of 36.6% at V2. The statistical analysis evidenced p values < 0.01 for times, treatments, time x treatments. The relevant results are summarized in Table 2. Erdosteine sachets 225 mg: concerning cough (primary end-point) in the group of patients (n = 50) treated with erdosteine it has been possible to point out a reduction of 17.6% at V1, i.e. after 3+/-1 days, and of 56.8% at V2, i.e. after 7+/-2 days. In the group of patients treated with placebo (n = 50) the reduction has been of 15.6% at V1 and of 31.8% at V2. The statistical analysis evidenced p values < 0.01 for times, treatments, time x treatments. (ABSTRACT TRUNCATED)