Ignite Creation Date:
2024-05-05 @ 5:26 PM
Last Modification Date:
2024-10-26 @ 9:31 AM
Study NCT ID:
NCT00453765
Status:
COMPLETED
Last Update Posted:
2013-04-08
First Post:
2007-03-28
Brief Title:
The Effect of Montelukast in Patients With Chronic Cough and Bronchial Hyperreactivity
Sponsor:
Isala
Organization:
Isala
Study Overview
Official Title:
Prospective Single-centre Double Blind Randomised Trial of Montelukast in Patients With Chronic Cough and Bronchial Hyperreactivity
Status:
COMPLETED
Status Verified Date:
2013-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
montelukast
Brief Summary:
The purpose is to determine whether montelukast during 6 weeks has superior antitussive effects measured with the LCQ compared with placebo in patients with cough lasting 8 weeks and enhanced bronchial hyperreactivity
Detailed Description:
Chronic cough is a frequent problem in general practice and one of the most common reasons for referral to a respiratory clinic Prospective studies have shown that the vast majority of cases of chronic cough are due to one or more of three conditions rhinitispostnasal drip syndrome asthma and gastro-oesophageal reflux disease Other significant causes of chronic cough include postviral post-infectious cough and eosinophilic bronchitis In only a minority of the patients with a chronic cough no cause can be found This is called idiopathic cough
Analysis and treatment of patients with chronic cough often proved to be difficult and disappointing Nevertheless centers in which a comprehensive diagnostic and therapeutic protocol was implemented reported excellent results Therefore the first cough clinic is started in The Isala Klinieken ZwolleThe Netherlands in 2004
Asthmatic cough is often accompanied by the more typical symptoms of dyspnoea and wheezing In a subgroup of asthmatics however cough is the sole or predominant symptom This condition is termed cough-variant asthma CVA Cough due to CVA usually improves within the first week of inhaled bronchodilator therapy however complete resolution of cough may require up to 8 weeks of combination therapy with inhaled bronchodilators and corticosteroids A subgroup of CVA patients with severe refractory cough may require systemic oral steroids alone or followed by inhaled therapy
Leukotrienes are contributing significantly to the pathobiology of asthma These pathways of asthma could be suppressed by leukotriene inhibitors Multiple clinical trials have demonstrated the ability of the leukotriene modifiers to improve symptoms pulmonary function and bronchial hyperresponsiveness in chronic asthma as well as in exercise-induced and aspirin-induced asthma Until recently the antitussive effects of this drug class had not been investigated properly Spector and Tan concluded in a pilot trial with only 14 patients that 10 mg montelukast seems to be effective in CVA However nowadays in care of asthma montelukast is widely used in a dosage of 10 mg Therefore we intend to study the effects of montelukast on chronic cough VAS-cough-score on a wider patient population is montelukast superior to placebo in the treatment of patients with chronic cough and a demonstrated bronchial hyperreactivity
Aim of the study
The purpose is to determine whether montelukast during 6 weeks has superior antitussive effects measured with the VAS cough compared with placebo in patients with cough lasting 8 weeks and enhanced bronchial hyperreactivity
Study design
Montelukast trial prospective single-centre double blind randomised trial
In the montelukast study 84 patients between 18 and 90 years old referred to the cough outpatient clinic with chronic cough and enhanced bronchial hyperreactivity will be recruited after informed consent is obtained
Patients will be randomised for gender age smoking duration of symptoms and the use of inhaled corticosteroids to 6- week treatment with 10 mg daily montelukast or placebo Before randomisation all patients have to fill in the Visual Analogue Scale VAS for detection of the degree of cough in the last 24 hours and the dutch version of the Leicester Cough Questionnaire LCQ for the detection of illness specific quality of life Adverse events will be noted in this period Finally both groups will be compared
Inhaled corticosteroids may be continued during the study at a constant dose Nasal ophthalmologic and dermatological steroids are allowed according to individual needs but their dose should be kept constant throughout the trial
H1 blockers nasal anticholinergics as well as nasal or ophthalmologic preparations of nedocromil or cromoglycate are permitted for treatment of allergic rhinitis
Study population
Patients between 18 and 90 years old referred to the cough outpatient clinic with chronic cough and enhanced bronchial hyperreactivity
Intervention
Patients between 16 and 90 years old referred to the cough outpatient clinic with chronic cough and enhanced bronchial hyperreactivity will receive daily montelukast 10 mg or placebo during 6 weeks
Main study endpoint
1 Difference in cough VAS scores montelukast vs placebo
Secondary study endpoints
1 Difference in average score on the Leicester Cough Questionaire LCQ between the two treatment groups montelukast vs placebo
2 Comparison of the adverse events of montelukast vs placebo
Randomisation
Patients will be randomised by a computer minimisation program for the following factors gender age smoking duration of symptoms and the use of inhaled corticosteroids
Statistical analysis
The primary analysis will be on an intention-to-treat basis The mean change in the primary endpoint LCQ total and domain scores after 6 weeks between the groups will be analysed using an unpaired t-test This test will also be used to analyse differences after 6 weeks in secondary endpoints VAS cough score
Since both the primary and secondary endpoints in the study will be measured more than two times repeatedly measured the course of these scores over time will be tested using MANOVA-analysis To test for differences in proportions proportion of patients with adverse events the Chi2 -test will be used Data analyses will be performed using SPSS version 12
Burden risks and advantages associated with participation
Side effects have been reported in 10 of the cases mostly of headache and abdominal pain Also gastrointestinal problems allergic reactions psychiatric disorders liver and haematological disorders could occur
Interactions Montelukast is metabolised by CYP3A4 Concomitant use of CYP3A4 inducing medication like fenytoïne phenobarbital or rifampicin must be prevented
Medication metabolised by CYP2C8 must also be avoided because in vitro studies have shown that montelukast is an powerful CYP2C8 inhibitor
Benefits superior resolution of cough compared to placebo
Analysis and treatment of patients with chronic cough often proved to be difficult and disappointing Nevertheless centers in which a comprehensive diagnostic and therapeutic protocol was implemented reported excellent results Therefore the first cough clinic is started in The Isala Klinieken ZwolleThe Netherlands in 2004
Asthmatic cough is often accompanied by the more typical symptoms of dyspnoea and wheezing In a subgroup of asthmatics however cough is the sole or predominant symptom This condition is termed cough-variant asthma CVA Cough due to CVA usually improves within the first week of inhaled bronchodilator therapy however complete resolution of cough may require up to 8 weeks of combination therapy with inhaled bronchodilators and corticosteroids A subgroup of CVA patients with severe refractory cough may require systemic oral steroids alone or followed by inhaled therapy
Leukotrienes are contributing significantly to the pathobiology of asthma These pathways of asthma could be suppressed by leukotriene inhibitors Multiple clinical trials have demonstrated the ability of the leukotriene modifiers to improve symptoms pulmonary function and bronchial hyperresponsiveness in chronic asthma as well as in exercise-induced and aspirin-induced asthma Until recently the antitussive effects of this drug class had not been investigated properly Spector and Tan concluded in a pilot trial with only 14 patients that 10 mg montelukast seems to be effective in CVA However nowadays in care of asthma montelukast is widely used in a dosage of 10 mg Therefore we intend to study the effects of montelukast on chronic cough VAS-cough-score on a wider patient population is montelukast superior to placebo in the treatment of patients with chronic cough and a demonstrated bronchial hyperreactivity
Aim of the study
The purpose is to determine whether montelukast during 6 weeks has superior antitussive effects measured with the VAS cough compared with placebo in patients with cough lasting 8 weeks and enhanced bronchial hyperreactivity
Study design
Montelukast trial prospective single-centre double blind randomised trial
In the montelukast study 84 patients between 18 and 90 years old referred to the cough outpatient clinic with chronic cough and enhanced bronchial hyperreactivity will be recruited after informed consent is obtained
Patients will be randomised for gender age smoking duration of symptoms and the use of inhaled corticosteroids to 6- week treatment with 10 mg daily montelukast or placebo Before randomisation all patients have to fill in the Visual Analogue Scale VAS for detection of the degree of cough in the last 24 hours and the dutch version of the Leicester Cough Questionnaire LCQ for the detection of illness specific quality of life Adverse events will be noted in this period Finally both groups will be compared
Inhaled corticosteroids may be continued during the study at a constant dose Nasal ophthalmologic and dermatological steroids are allowed according to individual needs but their dose should be kept constant throughout the trial
H1 blockers nasal anticholinergics as well as nasal or ophthalmologic preparations of nedocromil or cromoglycate are permitted for treatment of allergic rhinitis
Study population
Patients between 18 and 90 years old referred to the cough outpatient clinic with chronic cough and enhanced bronchial hyperreactivity
Intervention
Patients between 16 and 90 years old referred to the cough outpatient clinic with chronic cough and enhanced bronchial hyperreactivity will receive daily montelukast 10 mg or placebo during 6 weeks
Main study endpoint
1 Difference in cough VAS scores montelukast vs placebo
Secondary study endpoints
1 Difference in average score on the Leicester Cough Questionaire LCQ between the two treatment groups montelukast vs placebo
2 Comparison of the adverse events of montelukast vs placebo
Randomisation
Patients will be randomised by a computer minimisation program for the following factors gender age smoking duration of symptoms and the use of inhaled corticosteroids
Statistical analysis
The primary analysis will be on an intention-to-treat basis The mean change in the primary endpoint LCQ total and domain scores after 6 weeks between the groups will be analysed using an unpaired t-test This test will also be used to analyse differences after 6 weeks in secondary endpoints VAS cough score
Since both the primary and secondary endpoints in the study will be measured more than two times repeatedly measured the course of these scores over time will be tested using MANOVA-analysis To test for differences in proportions proportion of patients with adverse events the Chi2 -test will be used Data analyses will be performed using SPSS version 12
Burden risks and advantages associated with participation
Side effects have been reported in 10 of the cases mostly of headache and abdominal pain Also gastrointestinal problems allergic reactions psychiatric disorders liver and haematological disorders could occur
Interactions Montelukast is metabolised by CYP3A4 Concomitant use of CYP3A4 inducing medication like fenytoïne phenobarbital or rifampicin must be prevented
Medication metabolised by CYP2C8 must also be avoided because in vitro studies have shown that montelukast is an powerful CYP2C8 inhibitor
Benefits superior resolution of cough compared to placebo
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None