Leukotriene D4 Bronchial Provocation Test (LTD4-BPT) as an Indicator for the Use of Leukotriene Receptor Antagonist (LTRA)

Bronchial Asthma Clinical Trial

Official title:

Could Leukotriene D4 Bronchial Provocation Test be a Clear Indicator for Predicting Therapeutic Outcomes of Leukotriene Receptor Antagonist A Pilot Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01414868
• Other study ID #: LTD4-BPT20110806
• Status: Completed
• Phase: N/A
• First received: August 8, 2011
• Last updated: August 17, 2011
• Start date: March 2010
• Est. completion date: September 2010

Study information

• Verified date: December 2009
• Source: Guangzhou Institute of Respiratory Disease
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: September 2010
• Est. primary completion date: September 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Asthma
• Bronchial Asthma

Intervention

Drug:
• leukotriene receptor antagonist (montelukast)
montelukast (10 mg, once per night)

Locations

Country	Name	City	State
China	The First Affiliated Hospital of Guangzhou Medical College	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Guangzhou Institute of Respiratory Disease

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	whether there was improvement in weekly PEFR	The primary outcome was a qualitative measure, with the results being expressed as either yes or no ('1' or '0' in Logistic model).PEFR was defined as the changed rate of peak expiratory flow, which was calculated using the formula according to maximal PEF (PEFmax) and minimal PEF (PEFmin) measured by portable PEF monitor: 100%*(PEFmax-PEFmin)/[(PEFmax+PEFmin)*1/2]. A higher PEFR is more suggestive of instability of asthma control.	from commencement of LTRA therapy to (28±7) days	No
Secondary	whether there was improvement in post- treatment FENO	In Logistic regression model, whether there was improvement shown in post-treatment FENO as compared with pre-treatment level was expressed as either 'yes' or 'no', with symbols of '1' or '0'. Thus the measure was qualitative one. FENO represented fractional exhaled nitric oxide above.	from commencement of LTRA therapy to (28±7) days	No
Secondary	whether there was improvement in post- treatment PEF max	In Logistic regression model, whether there was improvement shown in post-treatment PEFmax as compared with pre-treatment level was expressed as either 'yes' or 'no', with symbols of '1' or '0'. Thus the measure was qualitative.	from commencement of LTRA therapy to (28±7) days	No
Secondary	whether there was improvement in post- treatment PEF min	In Logistic regression model, whether there was improvement shown in post-treatment PEFmin as compared with pre-treatment level was expressed as either 'yes' or 'no', with symbols of '1' or '0'. Thus the measure above was qualitative.	from commencement of LTRA therapy to (28±7) days	No
Secondary	whether there was improvement in post- treatment PD20FEV1-LTD4	In Logistic regression model, whether there was improvement shown in post-treatment PD20FEV1-LTD4 as compared with pre-treatment level was expressed as either 'yes' or 'no', with symbols of '1' or '0'. Thus the measure above was qualitative. PD20FEV1-LTD4 referred to as the provocative dosage causing a 20% fall in FEV1 while using Leukotriene D4 as a bronchoprovocant.	from commencement of LTRA therapy to (28±7) days	No
Secondary	whether there was improvement in post- treatment PD20FEV1-MCh	In Logistic regression model, whether there was improvement shown in post-treatment PD20FEV1-MCh as compared with pre-treatment level was expressed as either 'yes' or 'no', with symbols of '1' or '0'. Thus the measure above was qualitative. PD20FEV1-MCh referred to as the provocative dosage causing a 20% fall in FEV1 while using methacholine as a bronchoprovocant.	from commencement of LTRA therapy to (28±7) days	No
Secondary	whether there was improvement in post- treatment AQLQ symptom score	In Logistic regression model, whether there was improvement shown in post-treatment AQLQ symptom score as compared with pre-treatment level was expressed as either 'yes' or 'no', with symbols of '1' or '0'. Thus the measure above was qualitative. Items with regard to asthma symptoms were extracted from the whole AQLQ score, with the total score of 84. Higher score represented better asthma control.	from commencement of LTRA therapy to (28±7) days	No
Secondary	whether there was improvement in post- treatment ACT score	In Logistic regression model, whether there was improvement shown in post-treatment ACT score as compared with pre-treatment level was expressed as either 'yes' or 'no', with symbols of '1' or '0'. Thus the measure above was qualitative. The total score of ACT was 25, with 5 questions in all. Higher score was indicative of better asthma control.	from commencement of LTRA therapy to (28±7) days	No
Secondary	whether there was improvement in pre-challenge FEV1	In Logistic regression model, whether there was improvement shown in post-treatment pre-challenge FEV1 as compared with pre-treatment level was expressed as either 'yes' or 'no', with symbols of '1' or '0'. Thus the measure was qualitative one.	from commencement of LTRA therapy to (28±7) days	No
Secondary	whether there was a gradual decrease in weekly use of salbutamol	In Logistic regression model, whether there was a gradual decrease in weekly use of salbutamol as compared with pre-treatment level was expressed as either 'yes' or 'no', with symbols of '1' or '0'. Thus the measure was qualitative one.	from commencement of LTRA therapy to (28±7) days	No
Secondary	the days without using salbutamol	This was a quantitative parameter	from commencement of LTRA therapy to (28±7) days	No
Secondary	monthly PEFR	This was a quantitative parameter, which was expressed as percentage.	from commencement of LTRA therapy to (28±7) days	No