Effects of low-versus high-dose fluticasone propionate/formoterol fumarate combination therapy on AMP challenge in asthmatic patients: A double-blind, randomised clinical trial.
(2016) In Pulmonary Pharmacology & Therapeutics 37. p.65-72- Abstract
- BACKGROUND:
The dose-response relationship between two dose levels of fluticasone/formoterol (flutiform®, 100/10 μg and 500/20 μg) was evaluated in asthmatic patients. Non-invasive inflammatory markers were used including adenosine monophosphate (AMP) challenge (primary endpoint), and sputum eosinophils and fractional exhaled nitric oxide (FeNO) (secondary endpoints).
METHODS:
Patients aged ≥18 years with forced expiratory volume in 1 second (FEV1) ≥60% predicted and who required a dose of <60 mg AMP to elicit a 20% drop in FEV1 (AMP PD20) were randomised in this incomplete block, crossover study to receive 2 of 3 treatments b.i.d.: fluticasone/formoterol 500/20 μg (high dose), 100/10 μg... (More) - BACKGROUND:
The dose-response relationship between two dose levels of fluticasone/formoterol (flutiform®, 100/10 μg and 500/20 μg) was evaluated in asthmatic patients. Non-invasive inflammatory markers were used including adenosine monophosphate (AMP) challenge (primary endpoint), and sputum eosinophils and fractional exhaled nitric oxide (FeNO) (secondary endpoints).
METHODS:
Patients aged ≥18 years with forced expiratory volume in 1 second (FEV1) ≥60% predicted and who required a dose of <60 mg AMP to elicit a 20% drop in FEV1 (AMP PD20) were randomised in this incomplete block, crossover study to receive 2 of 3 treatments b.i.d.: fluticasone/formoterol 500/20 μg (high dose), 100/10 μg (low dose) or placebo, during 2 periods of 28±3 days each, separated by 2-3 weeks. AMP challenges were performed pre-dose and 12 hours after last dose at the end of each treatment period. A series of post hoc analyses were performed only in patients allocated to both fluticasone/formoterol doses, who completed the study and had evaluable AMP PD20 data for both treatments ("fluticasone/formoterol subgroup"). Changes in AMP PD20 FEV1, percentage sputum eosinophils and FeNO levels (day 1 vs day 28) between treatments were compared by an analysis of covariance (ANCOVA).
RESULTS:
Sixty-two patients were randomised and 46 completed the study. Fifteen patients received both high- and low-dose fluticasone/formoterol (post hoc subgroup). The difference in AMP PD20 for the overall population was not statistically significant between high- and low-dose fluticasone/formoterol (LS mean fold difference: 1.3; p=0.489), although both dose levels were superior to placebo: high-dose vs placebo LS mean fold difference: 4.4, p<0.001; low-dose vs placebo LS mean fold difference: 3.5, p<0.001. In the post hoc subgroup, the difference in AMP PD20 between the doses was statistically significant in favour of the high-dose (LS mean fold difference: 2.4, p=0.012). Other inflammatory parameters (sputum eosinophil counts and FeNO) showed small differences and statistically non-significant changes between high- and low-dose fluticasone/formoterol.
CONCLUSIONS:
A significant dose-response was found between low- and high-dose fluticasone/formoterol in the post hoc subgroup (patients who received both doses), but not in the overall population, with the higher dose demonstrating a greater reduction in airway responsiveness to AMP. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/8821730
- author
- Kanniess, Frank ; Diamant, Zuzana LU and Lomax, Mark
- organization
- publishing date
- 2016-02-18
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Pulmonary Pharmacology & Therapeutics
- volume
- 37
- pages
- 65 - 72
- publisher
- Elsevier
- external identifiers
-
- pmid:26912209
- scopus:84960173056
- pmid:26912209
- wos:000375516400010
- ISSN
- 1522-9629
- DOI
- 10.1016/j.pupt.2016.02.003
- language
- English
- LU publication?
- yes
- id
- 699b54c8-9b2a-474e-ac29-6a0cc0954aec (old id 8821730)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/26912209?dopt=Abstract
- date added to LUP
- 2016-04-01 13:30:14
- date last changed
- 2022-01-27 19:36:18
@article{699b54c8-9b2a-474e-ac29-6a0cc0954aec,
abstract = {{BACKGROUND:<br/><br>
<br/><br>
The dose-response relationship between two dose levels of fluticasone/formoterol (flutiform®, 100/10 μg and 500/20 μg) was evaluated in asthmatic patients. Non-invasive inflammatory markers were used including adenosine monophosphate (AMP) challenge (primary endpoint), and sputum eosinophils and fractional exhaled nitric oxide (FeNO) (secondary endpoints).<br/><br>
METHODS:<br/><br>
<br/><br>
Patients aged ≥18 years with forced expiratory volume in 1 second (FEV1) ≥60% predicted and who required a dose of <60 mg AMP to elicit a 20% drop in FEV1 (AMP PD20) were randomised in this incomplete block, crossover study to receive 2 of 3 treatments b.i.d.: fluticasone/formoterol 500/20 μg (high dose), 100/10 μg (low dose) or placebo, during 2 periods of 28±3 days each, separated by 2-3 weeks. AMP challenges were performed pre-dose and 12 hours after last dose at the end of each treatment period. A series of post hoc analyses were performed only in patients allocated to both fluticasone/formoterol doses, who completed the study and had evaluable AMP PD20 data for both treatments ("fluticasone/formoterol subgroup"). Changes in AMP PD20 FEV1, percentage sputum eosinophils and FeNO levels (day 1 vs day 28) between treatments were compared by an analysis of covariance (ANCOVA).<br/><br>
RESULTS:<br/><br>
<br/><br>
Sixty-two patients were randomised and 46 completed the study. Fifteen patients received both high- and low-dose fluticasone/formoterol (post hoc subgroup). The difference in AMP PD20 for the overall population was not statistically significant between high- and low-dose fluticasone/formoterol (LS mean fold difference: 1.3; p=0.489), although both dose levels were superior to placebo: high-dose vs placebo LS mean fold difference: 4.4, p<0.001; low-dose vs placebo LS mean fold difference: 3.5, p<0.001. In the post hoc subgroup, the difference in AMP PD20 between the doses was statistically significant in favour of the high-dose (LS mean fold difference: 2.4, p=0.012). Other inflammatory parameters (sputum eosinophil counts and FeNO) showed small differences and statistically non-significant changes between high- and low-dose fluticasone/formoterol.<br/><br>
CONCLUSIONS:<br/><br>
<br/><br>
A significant dose-response was found between low- and high-dose fluticasone/formoterol in the post hoc subgroup (patients who received both doses), but not in the overall population, with the higher dose demonstrating a greater reduction in airway responsiveness to AMP.}},
author = {{Kanniess, Frank and Diamant, Zuzana and Lomax, Mark}},
issn = {{1522-9629}},
language = {{eng}},
month = {{02}},
pages = {{65--72}},
publisher = {{Elsevier}},
series = {{Pulmonary Pharmacology & Therapeutics}},
title = {{Effects of low-versus high-dose fluticasone propionate/formoterol fumarate combination therapy on AMP challenge in asthmatic patients: A double-blind, randomised clinical trial.}},
url = {{http://dx.doi.org/10.1016/j.pupt.2016.02.003}},
doi = {{10.1016/j.pupt.2016.02.003}},
volume = {{37}},
year = {{2016}},
}