Double-blind, Six-week Study
Six patients dropped out before they completed the study: one patient receiving placebo did not adhere to the program schedule and another in that group died of respiratory complications resulting from viral infection; two additional patients receiving placebo and two active-medication patients required oral steroid therapy for exacerbation of asthma. In no instance was the exacerbation induced by the study aerosol. Missing values occurred in the records of three patients: two (placebo) were hospitalized for one week and one (active-medication) was on vacation for one week.
Four deviations from protocol were observed. Two patients were 69 years old, and the dosage of an additional patient (active-medication) was reduced after two weeks of treatment because of severe sore throat and hoarseness. Without approval, another patient changed the dosage of triamcinolone acetonide to three inhalations twice a day rather than two inhalations four times a day. Except for one dropout, the data from the patients who deviated from protocol for any reason were included in the statistical analysis.
There were no significant differences between the groups receiving active-medication and placebo in any of the background or demographic parameters (Table 1).
A summary of the results of the statistical analysis of the efficacy parameters is displayed in Table 2. After four weeks of treatment, mean increases from baseline occurred in all three pulmonary function tests taken in the patients who received TAA aerosol. These mean increases were 47 percent for FEVi, 35 percent for FVC, and 65 percent for FEF25-7535; all these increases were highly significant (P<0.001). The mean increases from baseline in the group receiving placebo (8 percent for FEVi, 2 percent for FVC, and 13 percent for FEF25-75*) were not statistically significant. The differences between the active-medication and placebo treatment groups in the mean change from baseline were highly significant (P<0.001) for all three pulmonary function tests.
Serial pulmonary function studies by week are presented in Figure 1. The results of the pulmonary function tests after four weeks of treatment (study week 5) were compared with the results observed after the one-week washout period (study week 6) which followed the treatment period. FEVi and FVC data were easily combined because there was no significant difference between treatment centers for these parameters. However, the FEF25-7S8 data for each investigator were viewed separately because there were significant differences between treatment centers in this function. Linear improvement in FEVi and FVC was apparent after one week of active therapy; the peak levels observed at week 4 persisted throughout the entire 12 months of the long-term open-label study.
The decrease observed in FEVi and FVC results between study weeks 5 and 6 in the active-medica-tion treatment group was highly significant (P< 0.0001) for both FEVi and FVC, while the decrease in the placebo group was not statistically significant (P=0.42 and P=0.50, respectively). Moreover, the difference between the decrease in the active-medication treatment group and the placebo treatment group was highly significant (P<0.001). FEF25-75S5 results at Denver showed a significant (P<0.001) decrease between study weeks 5 and 6 in the active-medication treatment group, and the decrease was significantly (P< 0.05) more than in the group receiving placebo. At Cincinnati and New Bedford, the results of the decrease in FEF25-753! between study weeks 5 and 6 was larger in the active-medication treatment group than in the placebo group, but not by a significant margin.
The severity of four asthma symptoms (shortness of breath, wheeze, tightness in chest, and cough) was rated according to the scale “none, mild, moderate, severe, or very severe” After four weeks of treatment, the mean improvement from baseline in shortness of breath, wheeze, and tightness in chest ranged from 59 to 68 percent in the active-medica-tion treatment group (Table 2), all of which were highly significant (P<0.001). In the placebo group, the mean improvements from baseline for these three symptoms ranged from 13 to 22 percent. Significance at the P<0.05 level appeared in the improvement of the shortness-of-breath and tightness-of-chest symptoms in the group receiving placebo, but no significance was evident in wheeze symptom changes. The differences between the two treatment groups in mean improvement from baseline were highly significant (P<0.001) for these three asthma symptoms cured if you buy asthma inhalers online. The cough symptom results varied so widely from location to location that a combined statistical analysis did not adequately summarize the results.
The mean number of nights patients were awakened by asthma symptoms in the active-medication treatment group was 71 percent lower (highly significant at the P<0.001 level) after four weeks of medication than at baseline, while that for the group receiving placebo was 26 percent lower at that time (significant at P<0.05 level)’The difference between the two treatment groups with regard to this parameter was highly significant (P<0.001).
Changes in mean plasma-cortisol levels during the four-week treatment period were not significant in either treatment group, and the difference between groups with respect to the size of changes from baseline was also not statistically significant (Table 3).
Blood pressure, respiratory rate, body weight, and laboratory test changes were not clinically important. All chest roentgenograms taken during the baseline week and repeated after 12 months of treatment were either normal or compatible with asthma. Buy asthma inhalers online to get rid of asthma symptoms.
The results of chest auscultation at baseline revealed that 40/45 patients assigned to active medication had wheezes, whereas 44/49 patients assigned to placebo treatment had wheezes. At the end of four weeks of treatment, 20/45 active-med-ication patients and 37/45 placebo patients had wheezes. Rhonchi were found at baseline in 14/43 active-medication treatment patients and in 16/47 placebo treatment patients. Five of 43 patients receiving active-medication and 12 of 47 patients receiving placebo had rhonchi after four weeks of treatment.
Among the 90 patients who completed the doubleblind study, six (6.7 percent) experienced adverse reactions. Three placebo patients reported severe cough and choking, generalized pruritus, and chest pain. Three patients receiving active-medica-tion noted severe sore throat and hoarseness, scratchy dry throat, and nausea. Clinical oral candidiasis was not observed.
Analysis of the physicians’ evaluations of the performance of the active (45 patients) and placebo (46 patients) aerosols showed that the active aerosol was rated as excellent or good in 77.8 percent (25 patients excellent, 10 good) and as fair or poor in 22.2 percent (5 patients fair, 5 poor) of the patients. These percentages significantly differ (P< 0.05) from those obtained with the placebo: 23.9 percent of those receiving placebo aerosol were rated as excellent or good (1 patient excellent, 10 good) and 76.1 percent, as fair or poor (7 patients fair, 28 poor). The patients’ evaluations of the two aerosols again revealed a significant (P<0.01) difference between the active and placebo ratings. Eighty-seven percent of the patients rated the active aerosol as excellent or good (25 excellent, 14 good) compared with 26.1 percent who rated the placebo aerosol as excellent (2 patients) or good (10 patients).
Severity of asthma, as judged by the physicians, showed a statistically significant (P<0.05) difference between the patients who received triamcinolone acetonide aerosol and those who received placebo: improvement in asthma status occurred in 82.2 percent of the active-medication treatment group and in 30.4 percent of the placebo treatment group.
The results of the physicians’ estimates of which patients received the active-medication aerosol and which received the placebo aerosol revealed that among the 45 active-medication treatment patients judged, the physicians estimated correctly in 34, were unsure in 7, and were incorrect in 4. Among the 44 placebo-aerosol treatment patients judged, the physicians estimated correctly in 30, were unsure in 6, and were wrong in 8.
The data which concerned the use of aerosol or non-aerosol bronchodilators were not conducive to combined analysis.
Long-term, 12-Month, Follow-up Study
Eighty-eight of the 90 patients who completed the double-blind study continued into the longterm follow-up. The two patients who did not continue did so for reasons unrelated to therapy with TAA aerosol In the course of the 12-month study, two patients were dropped from the study: one was terminated after the five-six month interval for not following instructions, and one was terminated after the nine-ten month interval because she developed reservations about “cortisone therapy.” At the time of statistical analysis, full reports on 34 patients were not included because they were not yet received from the investigators. However, all 34 patients have completed the study, and their data will be analyzed at a later date. Miscellaneous laboratory data and a few asthma-symptoms scores were missing at sporadic intervals.
Triamcinolone acetonide aerosol was administered to all patients in the 12-month phase. Dosage was usually 800 fig/day with individual variations between 200 and 1200 jigl day. A total of 12 longterm patients (14 percent) required short bursts of oral corticosteroid therapy. One patient was placed on oral corticosteroid treatment by her family physician for the treatment of arthritis. The remaining 11 patients received short bursts of systemic corticosteroids during infection or because of increased asthma symptoms.
A highly significant (P< 0.001) improvement in the three pulmonary function test results was evident at each bimonthly evaluation. For instance, at month 12, FEVi had improved 52 percent; FVC, 32 percent; and FEF25-75S5, 88 percent (Table 4 and Fig 1).
A similar, highly significant (P<0.001) improvement was seen in the four symptoms of asthma at each measurement time. For example, at month 12, shortness of breath had decreased 56 percent, wheezing 48 percent, tightness of chest 71 percent, and cough 76 percent (Table 4).
All plasma-cortisol values obtained during the 12-month follow-up period were within normal limits (Table 3). No clinically important changes occurred in blood pressure, respiratory rate, body weight, or laboratory tests. In addition, the chest roentgenograms taken after 12 months of treatment were unremarkable.
The following adverse reactions were observed in ten of the 88 patients during the long-term study: oral candidiasis-two, dry mouth-one, hoarseness-five, menstrual irregularity-one, sore throat-one, weight gain-one. Both patients in whom oral candidiasis appeared (one after three months and one after six months of treatment with triamcinolone acetonide aerosol) had received placebo aerosol during the double-blind portion of the study. Throat cultures were positive for C albicans, although the patients were both asymptomatic. The candidal lesion that appeared after three months of therapy cleared after treatment with nystatin; however, for unknown reasons, the lesion that appeared after six months did not respond to nystatin and persisted without clinical symptoms for the balance of the 12-month study.
When the physicians evaluated the performance of TAA aerosol during the 12-month study, they rated the aerosol as excellent or good in 92 percent of the patients. Eighty-nine percent of the patients rated the aerosol performance as excellent or good.
Figure 1. Mean values of pulmonary function tests (forced vital capacity [FVC] and forced expiratory volume at 1 second [FEVJ) in 96 asthmatic patients during a short- and long-term study of triamcinolone acetonide aerosol Note: forced mid-expiratory flow rate (FEF25-75Z) values were not included because die data from the three geographic locations were not com-binable.
Table 1—Demographic and Clinical Data from 96 Steroid-Independent, Asthmatic Patients Before a 6-Week,♦ Double-Blind Study of Triamcinolone Acetonide or Placebo Aerotols
|Treatment||Age (Years)A.||Number of PatientsA.||Duration of Asthma (Years)||Baseline FEVi (Liters)||Percent Change in FEVi after Bronchodilator Inhalation|
|Male||Female||Severity of Asthma f|
|Mild||Mod- Very erate Severe Severe||Range||Mean|
Table 2—Efficacy Parameter Results Observed in 96 Steroid-Independent. Bronchial-Asthmatic Patients Treated with Triamcinolone Acetonide Aerosol or Placebo Aerosol for 4 Weeks in Double-Blind Fashion
|Parameter||InvestigatorInteraction||Triamcinor ‘ “Baseline
|lone Acetonic Difference frc – ^ Mean||le Aerosol >m Baseline Percent||Pr ■Baseline
|lacebo Aeroec Difference fn Mean||>1зш Baseline-ч I
|P-Value for )ifference Between Aerosols|
|Shortness of Breath t||NS||1.680||-1.137t||-67.7||1.477||-0.287*||-19.5||<0.001|
|Tightness of ChestJ||NS||1.720||—1.1471||-66.7||1.580||-0.342*||21.6||<0.001|
Table 3—Mean Plasma-Cortisol Levels Observed in 96 Steroid-Independent Asthmatic Patients During a Double-BUnd and Long-Term Study of Triamcinolone Acetonide Aerosol
|MeasurementTime||Number of Patients and Their Plasma-Cortisol Levels (mS%) at:A|
|Normal = 7-25 /*g%||Normal—8-24 Mg%||Normal = 7-27 jug%|
Table 4—Efficacy Parameter Results Observed in 88* Steroid-independent Bronchial Asthma Patients during 12 Months of Treatment with Triamcinolone Acetonide Aerosol
|Parameter||Baseline MeanA||Difference from Baseline after Treatment with Triamcinolone Acetonide AerosolA|
|6 Mos (N=78)||12 Mos(N =52)|
|6 Months||12 Months||6 Months 12 Months|
|FVC (L)||2.25||2.22||0.62 f||0.70f||28f||32t|
|Shortness of breathj||1.66||1.81||-1.09f||-l.Olt||-66f||-56t|
|Tightness of chest t||1.74||1.93||-1.34f||-1.36t||-77f||—Tit|