Ketotifen in the young asthmatic--a double-blind placebo-controlled trial. Ketotifen for asthma in children aged 5 to 15 years: a randomized placebo-controlled trial. Multicenter study with ketotifen (Zaditen) oral drop solution in the treatment of wheezy children aged 6 months to 3 years. Effect of ketotifen on childhood asthma: a double-blind study. Long-term, placebo-controlled trial of ketotifen in the management of preschool children with asthma. Ketotifen in asthma. Ketotifen: a new drug for prophylaxis of asthma in children. Ketotifen in pollen-induced asthma: a double blind placebo-controlled study. Does ketotifen have a steroid-sparing effect in childhood asthma? Administration of half-dose theophylline together with ketotifen to asthmatic children--a double-blind, placebo-controlled study. Efficacy and safety of ketotifen in young children with asthma. A Canadian multicenter study with Zaditen (ketotifen) in the treatment of bronchial asthma in children aged 5 to 17 years. Efficacy of Zaditen (ketotifen) in wheezy infants and young children. The prophylactic treatment of bronchial asthma in children with ketotifen: a double-blind comparison with placebo. The effect of ketotifen on bronchial hyperreactivity in childhood asthma. A multicentre randomized placebo-controlled double-blind study on the efficacy of Ketotifen in infants with chronic cough or wheeze. A double blind placebo controlled study on the use of ketotifen in childhood asthma. A controlled comparison of slow-release theophylline, ketotifen and placebo in the prophylaxis of asthma in young children.
A double-blind placebo-controlled trial was carried out to assess the efficacy of ketotifen in the pre-school asthmatic. The trial period consisted of a 1-month run-in period followed by a 4-month treatment period. Symptom scores for asthma, rhinitis, eczema and, where possible, twice daily peak flow measurements (24 cases) were recorded on diary cards by the parents. All concomitant medication used in addition to the trial drug was noted. The only medication not allowed was disodium cromoglycate. A total of 37 children, 23 boys and 14 girls, mean age 4.1 years (range 1.3-5.9 years) completed the trial. They comprised 19 given ketotifen and 18 given placebo. All were atopic and had allergic rhinitis and 15 had eczema. Ketotifen dosage was 1 mg twice daily in the under 5-year-olds (23 cases) and 2 mg twice daily in the remainder. On analysing the results no significant benefit could be demonstrated for giving ketotifen in this group of patients. The prophylactic agent ketotifen has been studied in mild-to-moderate asthma. Various trials showed benefit from 10 to 12 weeks of therapy, but no trial in children with followup beyond 12 weeks of the drug is available.
                We studied the efficacy of ketotifen, 1 mg twice a day, orally as a prophylactic drug in children with asthma.
                The double-blind, placebo-controlled trial studied 120 asthmatic children of either sex between the ages of 5 to 15 years at a tertiary care hospital. After an observation period of 4 weeks, children were randomly assigned to receive either ketotifen, 1 mg twice a day, or placebo for 6 months. Antiasthma drugs were continued as required. Main outcome measures included average duration for regular antiasthma drugs, average symptom scores, symptom free days, peak expiratory flow rate, FEV1, and need for emergency room visits.
                Of the 120 children enrolled, 13 could not complete the trial. Thus 58 children remained in the treatment group and 49 were in the placebo group. Both groups were comparable in their baseline characteristics. The average number of days that required antiasthma drugs were significantly less in the treatment group: salbutamol (27+/-4.7 versus 37+/-3.5 P < .05), theophylline (37+/-4.7 versus 51+/-4.8 P < .05), oral steroids (2+/-0.4 versus 5+/-1.6 P < .05), and inhalation steroids (18+/-2.7 versus 16+/-10.8 P < .05). The average symptom scores and symptom free days for cough, wheeze, and breathlessness also favored the ketotifen group. Emergency room visits were also significantly lower in the ketotifen group (20 versus 10 P < .05). Statistically significant improvement in all the above parameters were observed after 14 weeks of therapy. The mean PEFR, FEV1 and side effects of medications were comparable between the two groups.
                Ketotifen, 1 mg twice a day, is an effective prophylaxis for asthma in children between 5 to 15 years. Significant clinical improvement is evident after 14 weeks of therapy. One hundred and seven chronically wheezing infants, aged 6 months to 3 years, completed a double-blind placebo controlled multicenter study. After a two-week baseline period the patients were randomized into two groups receiving twice daily either ketotifen or placebo for a period of 12 weeks. The ketotifen dosage was 0.5 mg for children younger than one year and 1 mg for the older. During the 12-week treatment period the patients from the two groups demonstrated gradual improvement of the disease severity parameters, as compared with the baseline period. The amelioration was more marked in the ketotifen treated patients and during the 0-4, and 4-8 weeks of treatment a significant decrease was achieved in the percentage of days with a cough (p < 0.04) and in the number of wheezing episodes (p = 0.02). Moreover, a 50% reduction of the days and nights with cough and in the number of wheezing episodes occurred earlier in the ketotifen than in the placebo treated patients, i.e. after 1.2 vs 4.6; 4.4 vs 8.6 and 5.2 vs 7.2 weeks, respectively. It should be stressed that the amelioration of the asthmatic morbidity in the ketotifen group was achieved with a significantly reduced need for the concomitant use of bronchodilators. The principal side effects observed were weight gain and transient sedation. It is concluded that ketotifen may be effective in the amelioration of asthma associated symptomatology and acceleration in the natural tendency for improvement in chronic wheezing infants. Ketotifen was administered orally, for 3 months, to 40 children aged 3-14 years with chronic extrinsic asthma of moderate severity in a double-blind placebo-controlled study. A significant clinical improvement with concomitant reduction of antiasthmatic drugs was found in the group receiving the active drug compared with the placebo group (p less than 0.05). The continued administration of ketotifen in an open study to a group of 21 children comprised of patients belonging to both groups (active-placebo) for a period of 15-18 months resulted in disappearance of symptoms in 10 children (47.6%) and moderate improvement in 7 (33.3%). Forty-seven children with chronic asthma, aged 2 to 6 years, completed a double-blind, placebo-controlled, crossover trial of ketotifen, 1 mg twice daily, in the prophylaxis of asthma. The study period covered two 24-week periods preceded by a 4-week run-in and separated by a 4-week washout. When symptoms, concomitant medication, frequency of acute exacerbations, and parental and physician preferences were analyzed, there were no significant differences between active and placebo treatments. The results suggest that ketotifen has no place in the management of young children with frequent asthma. Sixty children aged 5-13 years with moderately severe asthma took part in a double-blind, placebo-controlled trial of ketotifen. The design incorporated a 22 week study period, the addition of ketotifen or placebo to the current medication, and a controlled withdrawal of the regular therapy. Children receiving ketotifen showed significantly lower mean numbers of asthma attacks and less absence from school. The addition of ketotifen to existing treatment was associated with marginally significant changes in rates of day and night wheezing. In the second phase of study, additional therapy was withdrawn from both the ketotifen and placebo groups which resulted in a high (percentage) withdrawal. Children receiving ketotifen did not have a significantly lower failure rate than those given placebo. Ketotifen, an orally active, prophylactic anti-asthmatic drug, was compared with placebo in a double-blind, three-month parallel-group trial in 20 children. Children receiving ketotifen were more likely to reduce concomitant medications and had significant improvement over time in asthma scores and mean flows at 75%, 50%, and 25% of vital capacity. They also had a significantly increased incidence of dry mouth and significant weight gain compared to those receiving placebo. In some children with asthma, ketotifen may be a useful alternative to existing drugs. Twenty-nine children with an average age of 10.5 years were studied with respect to the protective effect of ketotifen on pollen-induced bronchial asthma. All of them were sensitive to deciduous tree pollen, the diagnosis being verified by bronchial challenge. The children were stratified in matched pairs and randomly allocated to two treatment groups, placebo or ketotifen 1 mg twice daily. The study was double-blind and was performed during the whole of the deciduous tree pollen season. Daily pollen counts were made, allergic symptoms were noted, additional medication was given and the expiratory pulmonary flow was recorded. During the birch pollen peak the ketotifen group showed significantly fewer, and less severe asthma and rhinoconjunctivitis than the placebo group. The anti-asthmatic medication was also used significantly less than in the placebo group. Ketotifen appeared to have good protective properties in the treatment of pollen-induced asthma and rhinoconjunctivitis. In view of the possible systemic side-effects of inhaled corticosteroids (ICS), a study was performed to determine whether ketotifen (versus placebo) can replace or allow a reduction in the dose of ICS required for the maintenance treatment of childhood asthma. Sixty six children (aged 6-13 yrs) with asthma (confirmed by methacholine challenge), who were maintained on ICS, at a dose of < or = 1 mg.day-1, were selected, and 52 subjects completed the trial. Children on long-term oral steroids or cromoglycate were excluded. After a 4 week baseline period, the children were randomized to receive ketotifen, 2 mg.day-1, or placebo for 32 Weeks. Between weeks 13-20 of the study, the daily dose of steroid was tapered by 25% every second week to the minimum dose tolerated by the patients. For the remainder of the study (Weeks 21-32) the patients continued on this dose (if tolerated). Beta 2-agonists were allowed, as necessary, for symptom relief. During the baseline period, the mean daily ICS dosage was 432 micrograms in the ketotifen group versus 408 micrograms in the placebo group (NS). Among the-patients who completed the study, the average ICS dosage during the final phase of the study (Weeks 21-32) was only 18% of baseline in the ketotifen group versus 35% in the placebo group (NS). Lung function, diurnal variability in peak flow rates and methacholine sensitivity (provocative concentration producing a 20% fall in forced expiratory volume in one second (PC20)) remained unchanged in both groups throughout the study. During the last 12 weeks of the study, the ketotifen-treated patients were symptomatically better controlled. In the present study, ketotifen did not have a greater steroid-sparing effect than placebo. Administration of theophylline to asthmatic children is frequently associated with an adverse influence on their behavior. The efficacy and behavioral effects of the administration of high-dose theophylline (T) and ketotifen (K) in various combinations were evaluated prospectively in a double-blind, placebo controlled study in 55 children with moderately severe perennial asthma. During a baseline period of 2 weeks, theophylline (serum level of 10-20 micrograms/ml) was administered to all the children. After this period the patients were randomly allocated into four comparable groups. The children were treated during a 12-week period with: T+K-Placebo (T group); T+K (T+K group); half-dose T+K (T/2 + K group); or placebo of both T and K (P group). During the 12-week treatment period, as compared to the baseline period, only the three groups of children who received active therapy (T+P, T+K, T/2 + K) showed a similar reduction in the number of days with asthmatic symptomatology, improvement of the total asthmatic symptoms score, and increased PEFR. The behavioral activity of the children (assessed by the Conner's rating scale) improved significantly only in the groups receiving placebo or T/2 + K. The results of this study suggest that a combination therapy of half the recommended therapeutic dose of theophylline with ketotifen can be clinically as effective as therapy with a full dose of theophylline, but with significantly less adverse behavioral effects. Thirty children (aged 1 to 3 years) with mild to moderate asthma were entered into a 28-week double-blind, crossover study comparing the prophylactic effect of ketotifen and placebo. A patient daily diary card was used to document symptoms and concomitant medications taken during a 2-week baseline and subsequent 12-week drug/placebo period. This was followed by a 2-week washout and 12 more weeks of drug/placebo in a crossover design. Physician assessment was performed at the beginning, at the end of each period, and at 4-week intervals throughout the drug study. No significant difference was observed between ketotifen treatment and placebo treatment in any of the study parameters that were tested. A decrease in concomitant medication usage during the first treatment period with ketotifen was observed. The principle side effect of ketotifen therapy observed in this age group was weight gain. In contrast to studies in adults, no sedation was noted. One hundred thirty-eight children with chronic asthma, requiring daily treatment with bronchodilators, took part in a 7-month, double-blind, multicenter clinical study. Patients were randomized into two groups, and after a 1-month baseline, were administered Zaditen (ketotifen), 1.0 mg twice daily, or an identical placebo for a period of 6 months. After 10 weeks of receiving the study medication, bronchodilator use was reduced or stopped. In the Zaditen-treated group, 60% of the children taking theophylline were able to stop its use completely, compared to 34% of the patients taking placebo (p less than 0.05). Of the patients who were unable to stop taking theophylline, the Zaditen-and placebo-treated groups recorded average dosage reductions of 62% and 26%, respectively. These differences were statistically significant (p less than 0.05). Thus, a high percentage of patients in the placebo-treated group maintained asthma symptom control with theophylline, whereas most of the Zaditen-treated patients could stop using this medication. Although pulmonary function readings improved in both groups, those patients taking Zaditen demonstrated earlier improvement and greater changes from baseline. Significant differences (p less than 0.05) in favor of Zaditen were found for reduction of concomitant medications, patient's global evaluation, physician's clinical evaluations, incidence of emergency room visits for asthma, and upper respiratory tract infections. No unexpected side effects were observed. It is concluded that Zaditen is an effective medication for long-term control of asthma in children. This was a double-blind, randomised evaluation of the efficacy and safety of Zaditen in comparison with placebo in infants and young children (aged 6-36 months). These children either had (i) at least 2 episodes of wheezing over 8 weeks, or (ii) persistent wheeze over 4 weeks, prior to entering into the study. In the doctor's opinion, the group treated with Zaditen had more improvement in symptomatology (p < 0.05). They were more likely to have reduced or discontinued bronchodilators. They showed trends of improvement of symptom scores in night cough, wheeze and sputum production. These differences, however, did not reach statistical significance. There were no major adverse reaction of note. Report on a double-blind parallel group comparison of ketotifen and placebo in two groups of twenty-five children with extrinsic bronchial asthma. Duration of treatment: 12 weeks, dosage adapted to body-weight, 0.5-1 mg b.i.d. Main parameters: Overall assessment of efficacy by the treating physician, total duration and frequency of asthmatic episodes per observation period. In all parameters ketotifen was far superior to placebo in spite of decreased concomitant bronchodilator therapy. The tolerance and acceptability of the compound was good. Eighteen children with perennial bronchial asthma with an average age of 9.6 yr were studied with respect to the protective effect of ketotifen on bronchial hyperreactivity. All children included demonstrated bronchial reversibility after inhalation of salbutamol, and the methacholine challenge produced a decrease of the forced expiratory volume during the first second of at least 20% in the concentration interval of 0.25 mg/ml to 4.0 mg/ml. The study was double-blind with patients divided into two parallel groups treated for 12 wk with ketotifen or placebo. Methacholine provocation tests were performed every fourth week during this period. No differences between the challenges before and during the treatment period were found in either group, nor were any differences found between the ketotifen and placebo groups. Long-term treatment with ketotifen does not appear to alter the bronchial hyperreactivity in children with bronchial asthma. The efficacy of Ketotifen was examined in the treatment of 113 infants between 6 and 36 months of age presenting with a history of cough and/or wheeze in a multicentre randomized placebo-controlled double-blind study. A 4 week no-medication baseline phase preceded the 16 week treatment phase in which infants took 2.5 mL twice daily of either placebo or Ketotifen (0.5 mg) syrup; this was followed by a 4 week wash-out phase. Diary card evaluation was performed by the parent or guardian for the duration of the study and recorded wheeze and cough twice daily as well as medication used. The percentage of symptom-free days decreased significantly in both groups (P < 0.005) with placebo-treated infants experiencing significantly more symptom-free days compared with the Ketotifen group (P < 0.01), although this difference was never more than 10% in any 4 week treatment period. Symptom severity scores and use of beta-agonist medication were also less in the placebo-treated infants but did not reach statistical significance. This study was unable to show a therapeutic advantage of Ketotifen over placebo in this group of infants with chronic cough and/or wheeze and the apparent statistical advantage of placebo is not a clinically relevant finding. nan A double blind crossover comparison of slow-release theophylline, ketotifen and placebo was carried out in 18 young children with perennial asthma. Theophylline significantly reduced symptoms and increased the mean peak expiratory flow rate. Transient nausea and vomiting was commoner during theophylline treatment but did not usually necessitate discontinuance of therapy.
Evidence from randomised controlled trials indicates that ketotifen alone or in combination with other co-interventions improves control of asthma and wheezing in children with mild and moderate asthma. However due to the high proportion of children with atopy in some trials the results cannot necessarily be generalised to all asthmatic children. The benefit is obtained at the cost of minor side effects, namely sedation and weight gain. The validity of this conclusion is limited by the low reported, methodological quality of included trials.