(Chest. 1999;116:1304-1312.)
© 1999
American College of Chest Physicians
A Controlled Trial of Chlorofluorocarbon-Free Triamcinolone Acetonide Inhalation Aerosol in the Treatment of Adult Patients With Persistent Asthma*
Michael Welch, MD;
David Bernstein, MD;
Gary Gross, MD;
Robert E. Kane, MS;
Donald Banerji, MD and
the
Azmacort HFA Study Group
*
From the Allergy & Asthma Medical Group & Research Center (Dr. Welch), San Diego, CA; Bernstein Clinical Research Center (Dr. Bernstein), Cincinnati, OH; Pharmaceutical Research & Consulting, Inc. (Dr. Gross), Dallas, TX; and Rhône-Poulenc Rorer (Mr. Kane and Dr. Banerji), Collegeville, PA.
A complete list of participants is located in the Appendix.
Correspondence to: Michael Welch, MD, Allergy & Asthma Medical Group & Research Center, 9610 Granite Ridge Dr, Suite B, San Diego, CA 92123; e-mail: mwelch{at}pol.net
 |
Abstract
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Study objective: To compare the dose response,
efficacy, and safety of inhaled triamcinolone acetonide (TAA) with a
hydrofluoroalkane (HFA) propellant (75 µg/puff), TAA with a
chlorofluorocarbon propellant (dichlorodifluoromethane [P-12]; 75
µg/puff), and placebo in adult patients with persistent asthma.
Design: Multicenter, randomized, double-blind,
placebo-controlled, parallel-group study of 514 adult patients with
persistent asthma.
Interventions and measurements:
Patients received 8 weeks of treatment with 150, 300, or 600 µg/d of
TAA HFA, the same doses of TAA P-12, or placebo following a 5- to
21-day baseline period. Efficacy was assessed by spirometry, and by
daily recordings of albuterol use, peak expiratory flow (PEF), asthma
symptom ratings, and nighttime awakenings throughout the study.
Results: Linear trend analysis showed that both
formulations of TAA at all doses produced statistically significant
improvements compared with placebo in spirometry, asthma symptom
scores, albuterol use, and PEF. Significant improvement was seen as
early as 24 h for morning PEF and as early as 1 week for
FEV1 (TAA HFA, 600 µg/d; TAA P-12, 300 and 600 µg/d)
and albuterol use (all doses of both formulations). The P-12 and HFA
formulations had comparable efficacy. A dose response showing greater
improvement with higher doses was evident for the majority of
parameters for both formulations. The incidences of adverse events were
similar across all treatment groups with no dose-related trends.
Conclusion: HFA and P-12 formulations of TAA inhalation
aerosol were therapeutically equivalent and showed comparable safety
and dose-related efficacy in the treatment of patients with persistent
asthma.
Key Words: asthma • chlorofluorocarbon • dichlorodifluoromethane • hydrofluoroalkane-134a • inhaled corticosteroids • triamcinolone acetonide
|
Introduction
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The
inhaled corticosteroid triamcinolone acetonide (TAA) has been available
since 1984 in the United States for the treatment of chronic asthma in
adults and children aged 
6 years.1
2
3
4
5
It is supplied
as a metered-dose inhaler (MDI) with an integrated spacer device using
the chlorofluorocarbon (CFC) propellant dichlorodifluoromethane (P-12).
Approximately 20% of asthma patients use inhaled corticosteroids, and
TAA accounts for a significant proportion of that use. In recent years,
CFCs including P-12 have been implicated in the destruction of the
stratospheric ozone layer; consequently, many nations including the
United States have agreed to replace CFCs in medicinal aerosols with
more environmentally friendly propellants.6
7
8
9
An
alternative propellant is hydrofluoroalkane-134a
(1,1,1,2-tetrafluoroethane; HFA), which has little potential for ozone
destruction and has been shown to have a favorable short-term toxicity
profile.10
Two new formulations of TAA (75 µg and 225 µg dosing strengths)
using HFA as a propellant (TAA HFA) have been developed as MDIs. The
TAA HFA formulations were developed to match the P-12 formulation in
dose delivery and particle size distribution, and use the same
integrated spacer device. The present study utilized the 75-µg TAA
HFA formulation, which is the same strength as the marketed P-12
formulation. The current method for determination of unit spray content
using the new United States Pharmacopoeia-tested device11
shows that both formulations deliver approximately 75 µg of TAA per
actuation from the mouthpiece (compared with 100 µg using the old
methodology). This investigation was designed to compare the efficacy
and tolerability of TAA HFA with those of placebo and TAA P-12 using
three different daily doses (150, 300, and 600 µg) in patients with
moderate asthma.
|
Materials and Methods
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Patient Selection
Eligible outpatients were aged 18 years, had chronic asthma
for 2 years, had required daily therapy with inhaled
corticosteroids for 30 days, and had an FEV1
of between 50% and 90% of the predicted value with 15% reversibility
following two puffs of albuterol. Patients who were current smokers or
who had a smoking history of 10 pack-years, life-threatening
asthma, upper respiratory infection within 30 days, acute exacerbation
of asthma, fungal infection, or other significant coexisting disease
were excluded. Women who were pregnant, lactating, or of childbearing
potential but not practicing an adequate method of birth control were
also excluded. The study protocol and informed consent were reviewed
and approved by an independent central institutional review board and
by boards associated with selected sites. Written informed consent was
obtained from all patients.
Study Medications
During the double-blind treatment period, patients were randomly
assigned to receive 1, 2, or 4 inhalations of HFA or P-12 formulations
of TAA bid (150, 300, or 600 µg/dl), or to receive 1, 2, or 4
inhalations of HFA-containing placebo bid. All patients received
single-blind HFA placebo treatment during the baseline period.
Albuterol inhalers were supplied for use as needed to control asthma
symptoms throughout the study.
Patients were not permitted to use any asthma medications other than
the study drug and albuterol inhaler. Patients who required additional
asthma medications or used more than 12 puffs of albuterol on 2
consecutive days were considered treatment failures. Patients taking a
stable regimen were allowed to continue immunotherapy. Patients were
also permitted to receive treatment with intranasal corticosteroids,
intranasal cromolyn sodium, antibiotics, and antihistamines.
Study Design
This was a double-blind, placebo-controlled study conducted at
39 centers in the United States. The study consisted of a screening
visit, a 5- to 21-day pretreatment baseline period, and an 8-week
treatment period. Patients discontinued their previously used inhaled
corticosteroid and received single-blind placebo inhaler treatment
during the baseline period. At visit one, informed consent was obtained
and medical, medication, and asthma history were recorded. Pulmonary
function tests and a physical examination including measurement of
height and weight were performed. All spirometry measurements were
performed after withholding albuterol for 6 h. For patients to
enter the baseline period, FEV1 must have been
within 50 to 90% of predicted. Blood and urine samples were collected
after an 8-h fast for hematology, blood chemistry, and urinalysis.
Eligible patients were required to demonstrate the proper use of an
MDI, and were instructed in the use of a Mini-Wright peak flow meter
(Clement Clarke International; Harlow, Essex, UK). They were
also provided with diaries, an albuterol inhaler for use only as needed
to control asthma symptoms, and placebo inhalers (HFA propellant) with
instructions to take one puff bid for the duration of the baseline
period. During baseline, patients measured and recorded morning and
evening peak expiratory flow (PEF) and recorded use of baseline study
medication (placebo inhaler), albuterol, and other concomitant
medication. Patients also recorded the number of nighttime awakenings
due to asthma, daytime and nighttime asthma symptoms, and any adverse
events. At the end of the baseline period, the following criteria were
required for randomization: FEV1 between 50% and
80% of predicted, 24 inhalations of albuterol during the last 4
days, and a total symptom score of 20 points (see "Efficacy and
Safety Variables") during the last 5 days of the baseline period.
During the 8-week treatment period, patients continued to record PEF,
symptom scores, nighttime awakenings, medication use, and adverse
events. Patients returned to the clinic every 14 days for mouth and
throat examination, assessment of pulmonary function, and review of
diary cards. At the final visit, patients underwent a posttreatment
physical examination, and blood and urine were collected for laboratory
analysis.
Efficacy and Safety Variables
The primary efficacy variables were mean change from baseline to
end point in FEV1 (% change) and albuterol use
(puffs per day). Other efficacy variables were as follows: mean change
from baseline to end point in forced expiratory flow in the middle half
of the FVC (FEF25–75%); morning and evening
PEF; daytime, nighttime, and 24-h symptom scores; and nighttime
awakenings. Asthma symptoms were rated on a 7-point scale (0 = no
symptoms to 6 = incapacitating symptoms requiring physician
intervention). Baseline was the last value before study drug treatment,
and end point was the last double-blind visit for
FEV1 and
FEF25–75%. For diary variables, baseline was
the average of values in the last 5 days of the baseline period (4 days
for albuterol use), and end point was the average over the last 7 days
of double-blind treatment. Mean changes from baseline to each visit or
each week were also determined.
Safety variables included adverse events recorded or reported by
patients, and changes in laboratory test results, vital signs, and
physical examination findings. In addition, all patients remained in
the clinic for a minimum of 30 min after inhalation of the first dose
of double-blind medication to be watched for any irritant effects on
the airways.
Statistical Analysis
The primary intent-to-treat analysis was the comparison of
active treatment with placebo within each formulation. A sample size of
78 patients per group was chosen to achieve an overall power of
90% (
= 0.05, two-sided) for the placebo vs active treatment
comparison with regards to FEV1. The difference
in the mean percent change in FEV1 values for the
active and placebo treatments was assumed to be 10% with an SD of
15%.
Analysis of variance (ANOVA), with treatment and center as main
effects, was used to assess center by treatment interaction for all
efficacy variables. In all cases, it was determined that
treatment-by-center interaction was not significant, and a one-way
ANOVA was used to determine treatment main effect for all variables,
for baseline to end point as well as for weekly analyses. Dose response
was assessed by using a one-sided linear trend test, and by pairwise
comparisons between doses within each treatment. Early onset of
efficacy for each group was assessed using two-sided paired
t tests to compare the last morning PEF prior to
randomization with PEF values 24 h and 48 h h after the first dose
of treatment. Onset of effect was similarly determined for daily
albuterol use on the second day after the beginning of treatment.
Three sets of analyses were performed to evaluate the comparability of
the HFA and P-12 formulations regarding five efficacy variables
(FEV1, albuterol use, morning PEF, number of
nighttime awakenings, and 24-h symptom scores). The first analyses
determined whether 90% or 95% confidence intervals fell within
predetermined therapeutic equivalence intervals to establish the
therapeutic equivalence of the same dose of the two formulations. A
one-way ANOVA model was used to compare all treatments, including
placebo. Because this analysis showed statistically significant
differences between active drug and placebo, averages (linear
combination) across the doses of the two formulations were tested to
determine the overall significance of comparisons between the two
formulations. The incidence of adverse events was analyzed using a
likelihood ratio test.
Clinical adverse events were summarized and analyzed based on
incidence. All laboratory tests were analyzed based on baseline-to-end
point data. Vital signs (respiration, BP, and pulse), weight, and
physical examination findings were summarized descriptively.
|
Results
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Demographics
Five hundred fourteen patients (315 women, 199 men; mean age, 39
years) were randomized and treated with double-blind study medication.
The seven groups were well matched for demographics, baseline
FEV1, and albuterol usage (Table 1
). Mean FEV1 was 2.2 L (65% of predicted) at the
end of the baseline period. The full 8-week treatment period was
completed by 419 of the 514 patients (81.5%). Thirty-four of the 95
patients (35.8%) who failed to complete the study were in the placebo
group. The reason for discontinuation was ineffectiveness of the test
drug in 75 patients, of whom 30 were in the placebo group, 19 in the
TAA P-12 150-µg group, and between 3 and 8 in each of the other P-12
and HFA groups (Table 2
). Fourteen patients were lost to follow-up. A total of six patients
discontinued study participation because of adverse events (three
placebo, two TAA P-12 300 µg, and one TAA HFA 600 µg).
Pulmonary Function
Patients taking both formulations of TAA at doses of 150, 300, and
600 µg/d showed significantly greater improvement in
FEV1 compared with those taking placebo (Fig 1
). The mean increase in FEV1 at the end of the
treatment period ranged from 12.3 to 22.0% for the HFA groups and from
14.4 to 24.8% for P-12.
The results of the analyses of the pulmonary function variables other
than FEV1 are shown in Table 3
. Morning PEF improved significantly in the HFA 150-, 300-, and
600-µg/d groups (by 9 L/min, 36 L/min, and 45 L/min, respectively),
compared with a decrease of 12 L/min in the placebo group. Evening PEF
also significantly increased by 9 to 33 L/min in the HFA groups,
compared with a decrease of about 8 L/min for placebo. Changes in
morning and evening PEF were similar in the HFA and P-12 groups, with
all doses showing statistically significant differences from
placebo. The increase in FEF25–75% was
significantly greater for only the 600-µg/d dosage of TAA HFA, and
for all doses of the P-12 formulation, compared with placebo.
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Table 3. Changes in Pulmonary Function From Baseline to End
Point: Comparisons Between TAA and Placebo in 514 Patients*
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|
Changes in FEV1 at each visit are shown in Figure 2
. Statistically significant improvement vs placebo was seen at week 1 in
the 600-µg/d HFA group (p < 0.005) and was maintained at all
visits (Fig 2
, top). The 300-µg/d group was significantly
better than the placebo group at week 2, but not at the other visits
(because the analysis was a linear trend test, the significance test
for the 150-µg group was not done if the 300-µg group was not
significantly different from the placebo group). The
FEV1 changes were significantly greater with 300
µg/d and 600 µg/d of P-12 than with placebo at all visits (Fig 2
,
Bottom).
Morning PEF showed significant improvement as early as 24 h after
the beginning of treatment with TAA HFA or TAA P-12 (Table 4 ). In the HFA groups, mean PEF increased by 8.6 to 20.2 L/min at 24
h and by 12.9 to 23.0 L/min at 48 h; the changes were
statistically significant for the 300- and 600-µg groups. The 150-
and 600-µg P-12 groups showed significant increases in morning PEF at
these times, but the small increase in the 300-µg group was not
statistically significant. The placebo group showed small decreases in
morning PEF at both 24 h and 48 h.
Bronchodilator Use
Statistically significant reductions (p < 0.005) in rescue
albuterol use were seen for all TAA HFA and P-12 groups compared with
placebo (Fig 3
). The reduction from baseline to end point ranged from 1.8 to 3.4
puffs/d for the HFA groups, and from 1.7 to 3.4 puffs/d for P-12; in
the placebo group, there was a small decrease of 0.4 puffs/d.
Changes in albuterol use after 48 h were not statistically
significant for any of the TAA groups, whereas mean albuterol
consumption in the placebo group increased by 1.3 puffs/d
(p < 0.001). By the end of week 1, albuterol use decreased
significantly in all dose groups of both formulations compared with
placebo (Fig 4
). Albuterol use decreased further during week 2 and trended downward
for the remainder of the study. The reductions were greater in the 300-
and 600-µg/d groups; in those groups, the decreases were
significantly greater compared with placebo during each week of the
study. The 150-µg/d groups were significantly different from placebo
only during weeks 1 to 3 (HFA) or weeks 1 and 3 (P-12), but not during
subsequent weeks when the placebo group showed a decline in mean
albuterol use, probably attributable to the discontinuation of
treatment failures.
Asthma Symptoms
Daytime, evening, and 24-h asthma severity scores improved
significantly at the end of treatment (p < 0.05) in all groups
treated with TAA HFA compared with the placebo group (Table 5
). Nocturnal awakenings were also significantly decreased across all
treatment groups. The P-12 groups showed very similar results, except
that the change in daytime symptom score was not statistically
significant for the 150-µg/d group.
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Table 5. Changes in Asthma Symptoms From Baseline to End
Point: Comparisons Between TAA and Placebo in 514 Patients*
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Dose Response
Linear trend test results showed dose-response trends for TAA HFA
and TAA P-12. All doses were significantly different from placebo, with
greater improvement at higher doses for most efficacy variables,
including morning and evening PEF (Table 3)
; daytime, nighttime, and
24-h asthma symptom score; and nighttime awakenings (Table 5
).
The results of pairwise comparisons also demonstrate dose response for
both formulations (Table 6
). The HFA 600-µg/d group showed significantly greater improvement
than the 150-µg/d group in all efficacy variables except
FEV1 and FEF25–75%.
Differences between the 600- and 300-µg/d dosages were significant
for FEV1, FEF25–75%, and
daytime symptom scores, and the 300- and 150-µg/d dosages were
significantly different for morning and evening PEF, albuterol use, and
nighttime awakenings. The pairwise comparisons between P-12 groups
showed similar results, with the high and low doses showing significant
differences for most variables. The medium and low doses of P-12 were
significantly different for three of the nine comparisons, but no
statistically significant differences were found between the 600- and
300-µg/d dosages of P-12.
Comparisons Between Formulations
The three methods used to compare the HFA and P-12 formulations
show results supporting equivalence. The analyses based on 95%
confidence intervals showed that the two formulations were
therapeutically equivalent at all three doses with regard to albuterol
use (therapeutic interval, ± 2 puffs) and nighttime awakenings
(therapeutic interval, ± 0.5 awakenings/night). Using the same
analysis, therapeutic equivalence could not be demonstrated for
FEV1 (therapeutic interval, ± 5%); morning PEF
(therapeutic interval, ± 20 L/min); and 24-h symptom scores
(therapeutic interval, ± 0.5 U), although mean changes were similar
in both formulations, and confidence intervals overlapped zero
difference in all cases.
No significant differences between formulations were found using the
ANOVA model, while the overall difference between active treatments and
placebo was highly significant (p < 0.001) for all five outcome
measures examined. The linear regression model showed similarity
between formulations in FEV1, albuterol use, and
morning PEF, with parallel regression lines and overlapping 95%
confidence bands across all dose levels. For 24-h symptom scores, the
confidence bands overlapped at the two lower doses but not at the
600-µg dose.
Tolerability
Overall, the incidence of adverse events in the combined TAA
groups (P-12 and HFA) were comparable (53.8% and 56.6%,
respectively), but slightly higher than in the placebo group (48.7%).
Because of a higher dropout rate in the placebo group, the extent of
exposure was less for the placebo group than for any of the TAA groups.
There were no trends toward increasing adverse event incidence with
increasing dose level of either formulation. In fact, for TAA HFA, the
lowest incidence of adverse events (49%) was at the 600-µg dose.
The incidence of adverse events related to the mouth and throat was low
in all groups. "Pharyngitis," which includes events such as "sore
throat" and "strep throat," was reported in four placebo
patients, and between two and five patients in each of the active
groups. Three cases of oral monilia were reported—one each in the P-12
150-µg, P-12 600- µg, and HFA 600-µg groups. Voice alterations
were reported in 10 patients—5 each in the P-12 and HFA groups. Five
patients reported adverse events during the 30-min observation period
after the first dose of study drug. The events were mild dry mouth
(P-12 150 µg and HFA 150 µg), moderate nasal congestion (placebo),
mild tingling sensation in tongue (HFA 600 µg), and mild vertigo (HFA
300 µg).
Six patients withdrew from the study because of adverse events. Four of
these were respiratory events: pneumonia and asthma exacerbation (P-12
300 µg); chest congestion and raspy throat (placebo); upper
respiratory infection (placebo); and cough (HFA 600 µg). One patient
(P-12 300 µg) withdrew because of a range of symptoms including
headaches, generalized edema, anxiety, and insomnia. The sixth patient
(placebo) withdrew because of poison ivy. None of these adverse events
were thought to be related to the study medication. There were two
serious adverse events: anxiety (P-12 300 µg) and acute exacerbation
of asthma (HFA 300 µg). Both serious adverse events were considered
unrelated to the study drug.
No clinically significant changes in laboratory values, vital signs, or
physical examination fingings were observed in any of the treatment
groups.
|
Discussion
|
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The results of this study showed that both the HFA and P-12
formulations of TAA were significantly more effective than placebo in
improving lung function and decreasing asthma symptoms.
FEV1 and morning and evening PEF showed
statistically significant improvements in the active groups compared
with the placebo group at all three dosing levels. Asthma symptom
scores and nighttime awakenings also showed consistent, statistically
significant improvement compared with placebo, along with decreased use
of albuterol in the TAA groups.
The TAA HFA 75 µg product was formulated specifically to replace the
CFC-containing product. The HFA and P-12 formulations of TAA appear to
be comparable based on the results of this study. Comparisons across
formulations incorporating all treatment groups indicated no
statistically significant or clinically significant efficacy
differences between the two formulations. In particular, therapeutic
equivalence was demonstrated across formulations for albuterol use and
nighttime awakenings. The relatively stringent therapeutic intervals
chosen partly explain the failure to show equivalence for the other
variables. The results of regression analyses were consistent with
those of the other two analyses, ie, both formulations were
comparable at all doses.
It is well known that it is difficult to demonstrate clear
dose-response effects for improvement in lung function with inhaled
corticosteroids. The review by Pedersen and O’Byrne12
pointed out that 9 of 10 published efficacy studies of inhaled
corticosteroids have failed to show statistically significant
differences between the clinical effects of adjacent dose steps. The
reasons for failure to demonstrate significant dose response in
previous studies could depend on a number of factors, such as severity
of the disease itself, prior treatment with inhaled steroids, length of
treatment period, or small patient sample size. In this study, however,
a dose response was evident for both formulations, with the high dosage
(600 µg/d) showing significantly greater improvement than the low
dosage (150 µg/d) for the majority of parameters. Statistically
significant dose-response differences were also demonstrated between
adjacent doses of TAA HFA for several variables. The same was true for
the low and middle doses of TAA P-12, but no significant differences in
any of the variables were found between the 300-µg and 600-µg
doses. Similar results were reported in an earlier study of TAA P-12,
with significant differences between doses for albuterol use but not
for FEV1 or symptom scores.13
Significant differences in response between different doses have also
been reported in studies of budesonide and fluticasone
propionate.14
15
The significant differences in FEV1 and
FEF25–75% between the 300- and 600-µg doses
of TAA HFA are notable because the 150- and 600-µg doses did not
significantly differ for these variables. These unexpected findings are
probably attributable to the fact that FEV1 and
FEF25–75% increased more in the 150-µg group
than in the 300-µg group, which in turn may have been due to the fact
that baseline values for both parameters were higher in the 300-µg
group than in any of the other groups. This higher baseline did not
allow for as large an improvement for the 300-µg group. Lung function
improvement as measured by morning and evening PEF, on the other hand,
was significantly greater in the 300-µg group than in the 150-µg
TAA group, just the opposite of the result seen for
FEV1 and FEF25–75%.
Inhaled corticosteroids must be taken regularly to effectively control
asthma,16
and for that reason the effects of inhaled
corticosteroids are generally thought to occur gradually over a period
of weeks or months.17
In the current study, both
formulations showed statistically significant improvement in
FEV1 as early as the first return visit, 1 week
after the start of treatment. Albuterol use was significantly decreased
as well by the end of 1 week at all doses of TAA. Even earlier onset of
effect was evident by the significant improvement in morning PEF at
24 h and 48 h. The few asthma studies that have reported on
changes in efficacy variables during the first days after the beginning
of corticosteroid treatment show similar results, with beneficial
effects within 48 h of starting treatment18
or even
earlier.19
Our findings of onset of effect within 24
h after the start of TAA HFA are in accord with previous studies of
intranasal TAA in patients with allergic rhinitis.20
21
22
Both treatments were well tolerated: the minimal occurrences of adverse
events in the active groups were not clinically different from placebo.
There was no evidence of increased incidence of adverse events with
increasing dose of either formulation of TAA. This study was not
designed to assess the relative systemic effects of the HFA and CFC
formulations. A previous study in asthmatic adults showed very small
decreases in cosyntropin stimulation test results after 6 or 12 months
of treatment with TAA HFA.23
Another study in children
treated with TAA HFA or TAA CFC for 6 weeks showed no difference in
response to cosyntropin between the two formulations.24
These results and those of the current study lead us to conclude that
the formulation of TAA inhalation aerosol using HFA-134a as propellant
is as efficacious and safe in the treatment of persistent asthma as the
marketed CFC formulation.
|
Appendix 1
|
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The Azmacort HFA Study Group consisted of 39 clinical research
centers in the United States. The principal investigators at the 39
centers are as follows: Donald Aaronson, MD, Des Plaines, IL; Howard
Offenberg, MD, Gainesville, FL; Donald Auerbach, MD, Cherry Hill, NJ;
John Oppenheimer, MD, Morristown, NJ; Thomas Bell, MD, Missoula, MT;
Peter Petroff, MD, San Antonio, TX; George Bensch, MD, Stockton, CA;
Frank Picone, MD, Tinton Falls, NJ; William Berger, MD, Mission Viejo,
CA; Stephen Pollard, MD, Louisville, KY; David Bernstein, MD,
Cincinnati, OH; Gordon Raphael, MD, Bethesda, MD; Jacques Caldwell, MD,
Daytona Beach, FL; Robert Rhodes, MD, Martinez, GA; Robert Cohen, MD,
Lawrenceville, GA; Richard Rosenthal, MD, Fairfax, VA; Leonard Cosmo,
MD, Tampa, FL; Eric Schenkel, MD, Easton, PA; Frank Demarco, Jr., MD,
Wheat Ridge, CO; Nathan Segall, MD, Atlanta, GA; Thomas Edwards, MD,
Albany, NY; Guy Settipane, MD, Providence, RI; Stanley Fineman, MD,
Marietta, GA; William Silvers, MD, Englewood, CO; Marc Goldstein, MD,
Mt. Laurel, NJ; Tommy Sim, MD, Galveston, TX; Gary Gross, MD, Dallas,
TX; William Sokol, MD, Newport Beach, CA; Dan Henry, MD, Salt Lake
City, UT; Sheldon Spector, MD, Los Angeles, CA; Robert Jacobs, MD. San
Antonio, TX; Paul Steinberg, MD, Minneapolis, MN; Michael Kraemer, MD,
Spokane, WA; William Stricker, MD, Rolla, MO; Craig LaForce, MD,
Raleigh, NC; Michael Wein, MD, Vero Beach, FL; Bruce Martin, DO, San
Antonio, TX; Michael Welch, MD, San Diego, CA; Michael Noonan, MD,
Portland, OR.
|
Footnotes
|
|---|
Abbreviations: ANOVA = analysis of variance;
CFC = chlorofluorocarbon; FEF25–75% = forced
expiratory flow in the middle half of the FVC;
HFA = hydrofluoroalkane-134a; MDI = metered-dose inhaler;
P-12 = dichlorodifluoromethane; PEF = peak expiratory flow;
TAA = triamcinolone acetonide
This trial was supported by contracts between Rhône-Poulenc Rorer
Pharmaceuticals, Inc., Collegeville, PA, and the individual clinical
investigators or their institutions.
Received for publication March 12, 1999.
Accepted for publication June 10, 1999.
|
References
|
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Bernstein, DI, Cohen, R, Ginchansky, E, et al (1998) A multicenter, placebo-controlled study of twice daily triamcinolone acetonide (800 µg per day) for the treatment of patients with mild-to-moderate asthma. J Allergy Clin Immunol 101,433-438[CrossRef][ISI][Medline]
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Bernstein, IL, Chervinsky, P, Falliers, CJ (1982) Efficacy and safety of triamcinolone acetonide aerosol in chronic asthma: results of a multicenter, short-term controlled and long-term open study. Chest 81,20-26[Abstract/Free Full Text]
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Falliers, CJ, Petraco, AJ (1982) Control of asthma with triamcinolone acetonide aerosol inhalations at 12 hour intervals. J Asthma 19,241-247[Medline]
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Abstract
Introduction
