Ketotifen in the Prophylaxis of Extrinsic Bronchial Asthma: Design of Study
Design of Study
The study was a double-blind, randomized, controlled multicenter study (22 centers in nine European countries) comparing a slow-release oral formulation of ketotifen with placebo for a period of 12 weeks in patients with mild extrinsic bronchial asthma. The dosing regimen for the slow-release oral tablet of ketotifen was based on the known efficacy of twice daily administration of 1 mg of ketotifen. A treatment duration of 12 weeks was selected based on previous controlled studies proving the efficacy of prophylactic treatments in bronchial asthma. The patients (in the case of children, their parents or guardians) volunteered for the trial after an explanation of the protocol, which was approved by the hospitals’ ethics committees. Oral consent was obtained from each participant.
Patients were examined at two-week intervals up to the end of the treatment period (week 12). At each of the seven visits, investigators scored asthmatic symptoms, dyspnea, cough, sputum, nasal discharge, and obstruction; examined the thorax; monitored vital signs; and questioned the patients about compliance (control of the drug usage) and adverse effects. Pulmonary function tests (PEFR, FEVIS FEV/FVC, FVC, and expiratory flow rates) were done at each visit at the same time of the day. The patients (in the case of children, their parents or guardians) kept a daily record of the occurrence and severity of asthmatic attacks, dyspnea, cough, nasal symptoms, and adverse effects and recorded any use of other drugs (concomitant medication) (0 = none; 1 = bronchodilating agents; 2=corticosteroids; and 3=drugs not allowed). Patients used Wright peak flow minimeters three times per day before inhalation of p-sympathomimetics, and the best of these three peak flow measurements was recorded. The overall effectiveness, based on the evaluation of clinical and functional response, was determined by the investigator using a scale of zero to four (0=none; 1 = slight; 2=moderate; 3=good; and 4=very good). Laboratory evaluations were done before and after the 12-week treatment period.
Tolerability and Compliance
All appropriate details regarding any adverse events were recorded. Laboratory tests of hematopoietic, hepatic, and renal function were done prior to therapy, as well as at the end of the trial. Adequate compliance with the prophylactic treatment of patients with bronchial asthma is very important. At each visit the investigator questioned the patient about compliance, as well as asking the patient to show the remaining tablets, so that control of drug usage was monitored.