Clinical trial NCT01414868: Leukotriene D4 Bronchial Provocation Test (LTD4-BPT) as an Indicator for the Use of Leukotriene Receptor Antagonist (LTRA)
Official title: Could Leukotriene D4 Bronchial Provocation Test be a Clear Indicator for Predicting Therapeutic Outcomes of Leukotriene Receptor Antagonist A Pilot Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Bronchial Asthma
Keywords: Leukotriene
leukotriene receptor antagonist
bronchial provocation test
therapeutic outcome
Lead sponsor: Guangzhou Institute of Respiratory Disease
Sponsor class: OTHER
First posted: 2011-08-11
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: Background: Therapeutic outcomes of leukotriene receptor antagonist (LTRA) vary in asthmatics，and there's not an ideal and simple way for prediction at present.

Objective：To investigate whether leukotriene D4 bronchial provocation test (LTD4-BPT) could be an indicator of actual therapeutic outcome of LTRA.

Methods：A single centre, open-labeled trial was performed in 32 asthmatics with positive LTD4-BPT result for a month. All subjects were categorized according to airway responsiveness to leukotriene D4（PD20FEV1-LTD4）. Subjects received montelukast therapy (10mg, once per night), and reassessment was performed (3\~5) days after withholding LTRA. The primary end-point was the difference in monthly PEFR. Secondary endpoints included the difference in FENO, PD20FEV1-LTD4, PD20FEV1-MCh, pre-test FEV1, ACT score, AQLQ symptom score, week 4 PEFmax and PEFmin as compared with week 1, gradual decrease in the use of salbutamol and the days without using salbutamol.

Detailed description: Our primary goal was to determine whether LTD4-BPT could be a clear indicator for assessing efficacy of LTRA. Logistic regression model was adopted for statistical analysis. In this model, pre-treatment PD20FEV1-LTD4 represented anticipated efficacy. The median of PD20FEV1-LTD4 was used for classification of asthmatics, with a lower figure representing a better anticipated outcome. Various variables, including the difference in pre- and post- treatment FENO, PEFmax, PEFmin, PEFR, PD20FEV1 and asthma scores, were introduced in the model representing the actual efficacy of LTRA. We aimed to test whether there would be certain parameters that assist prediction of anticipated outcome.

Eligibility criteria: Inclusion Criteria:

* subjects aged between 18 and 65，without acute upper respiratory tract infection for the past 2 weeks
* had a normal chest radiographic result
* had a baseline spirometry with the forced expiratory volume in one second (FEV1) of not less than 60% predicted
* had withheld leukotriene receptor antagonists (LTRA) for over 5 days
* oral glucocorticosteroid or anti-histamine for 3 days
* oral xanthenes or long-acting bronchodilators for 2 days
* inhaled corticosteroid or long-acting bronchodilator for a day as well as short-acting bronchodilator for 4 hours prior to the measurement

Exclusion Criteria:

* subjects had a fall of no less than 15% in FEV1 after repetitive forced respiration or a fall of no less than 20% in FEV1 after the inhalation of ethanol diluent control
* had a past confirmed history of respiratory disease other than bronchial asthma (COPD, bronchiectasis, pulmonary thromboembolism, etc.) or other severe systemic disease（myocardial infarction, malignant tumor, etc.）
* had a poor cooperation to the test or limited understandings, were immunocompromised, or had participated other clinical trials for the past 3 months.

Primary outcomes:
measure: whether there was improvement in weekly PEFR
timeFrame: from commencement of LTRA therapy to (28±7) days
Secondary outcomes:
measure: whether there was improvement in post- treatment FENO
timeFrame: from commencement of LTRA therapy to (28±7) days
measure: whether there was improvement in post- treatment PEF max
timeFrame: from commencement of LTRA therapy to (28±7) days
measure: whether there was improvement in post- treatment PEF min
timeFrame: from commencement of LTRA therapy to (28±7) days
measure: whether there was improvement in post- treatment PD20FEV1-LTD4
timeFrame: from commencement of LTRA therapy to (28±7) days
measure: whether there was improvement in post- treatment PD20FEV1-MCh
timeFrame: from commencement of LTRA therapy to (28±7) days
measure: whether there was improvement in post- treatment AQLQ symptom score
timeFrame: from commencement of LTRA therapy to (28±7) days
measure: whether there was improvement in post- treatment ACT score
timeFrame: from commencement of LTRA therapy to (28±7) days
measure: whether there was improvement in pre-challenge FEV1
timeFrame: from commencement of LTRA therapy to (28±7) days
measure: whether there was a gradual decrease in weekly use of salbutamol
timeFrame: from commencement of LTRA therapy to (28±7) days
measure: the days without using salbutamol
timeFrame: from commencement of LTRA therapy to (28±7) days
measure: monthly PEFR
timeFrame: from commencement of LTRA therapy to (28±7) days
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Guangzhou Medical College
state: Guangdong
Study officials:
References:
citation: Guan WJ, Shi X, Zheng JP, Gao Y, Jiang CY, Xie YQ, Liu QX, Zhu Z, Guo E, An JY, Yu XX, Liu WT, Zhong NS. Leukotriene D4 inhalation challenge for predicting short-term efficacy of montelukast: a pilot study. Clin Respir J. 2015 Jan;9(1):111-20. doi: 10.1111/crj.12117. Epub 2014 Mar 5.