Since coughing is the major symptom in BE, the objective of this trial is to evaluate the clinical efficacy of ICS/LABA treatment in subjects with BE on coughing. The primary outcome variables of interest is the Leicester cough questionnaire (LCQ),…
ID
Source
Brief title
Condition
- Respiratory tract infections
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Leicester cough questionnaire
Secondary outcome
Quality of Life Bronchiectasis (QOL-B) questionnaire*s respiratory symptom
domain
pulmonary function (FEV1)
the frequency of exacerbation requiring an intervention with systemic
antibiotics (oral/intravenous [i.v.])
24 hour sputum production (in mL);
dyspnea score using mMRC (Modified Medical Research Council)
adverse events
Assessing the inflammatory respons by analysing blood and sputum
Background summary
Bronchiectasis (BE) is a chronic disorder of the bronchi and bronchioles. BE
has been defined as a rare disease. It is characterized by permanent dilation
involving a degenerative vicious cycle of microbial infection and persistent
inflammatory response with the release of immune mediators and microbial
toxins.
Clinically, patients complain about a (productive) cough that can yield large
volumes of mucopurulent sputum, next to dyspnoea. Coughing is the major symptom
in BE. Furthermore, haemoptysis can occur, sometimes patients have pleuritic
chest pain, and wheezing. Fatigue is a frequent complaint, and acute
exacerbations of airway symptoms are common. This chronic disease poses a large
burden for the patient and for society because of the morbidity that includes
work absences, reduced physical performance, and social distress.
The reported prevalence is largely unknown, but commonly seen in regular
pulmonary practise. BE is usually diagnosed in middle aged and elderly
patients, more female than male are affected. The golden standard for diagnosis
is the high-resolution computed tomography (HRCT) scans.
The causes of BE are numerous. One of the most common causes is a previous
respiratory tract infection with adenovirus, measles, influenza, Bordetella
Pertussis, Staphylococcus aureus, Mycobacterium tuberculosis, Streptococcus
pneumonia, or other bacterial pathogens, resulting in lung damage. But up to 50
- 80% of cases of BE are considered to be of idiopathic origin. Hence, the
etiology of BE can be categorized as idiopathic, post-infectious, or due to an
underlying anatomic or systemic disease.
The management of BE requires treatment of the underlying cause and to prevent
and treat recurrent infection. Currently, the management consists of bronchial
hygiene either pharmacologically or mechanically, administration of courses of
pathogen directed antibiotic treatment and maintenance treatment with
macrolides to prevent new exacerbations. In real-life setting however,
approximately 60% of BE patients in the EMBARC registry
(https://www.bronchiectasis.eu) showed that they received a long acting
bronchodilator (LABA) and almost as many were in receipt of an inhaled
corticosteroid (ICS). Most of the pharmacotherapy are based on the empirical
treatment for COPD or asthma. In patients with asthma or COPD, ICS and LABAs
have proven to be beneficial for a subgroup of patients in terms of improvement
of health-related quality of life and reduction of exacerbations.
In the management of BE, bronchodilator treatment and use of inhaled steroids
is still a matter of debate, as only one long-term randomized parallel-group
controlled trial has been performed. Martinez-Garcia published a prospective
double blind study in which non-CF BE patients were randomised to either
combined formoterol and medium dose budesonide (18/640mcg daily), or budesonide
(1600mcg) alone by Turbuhaler. In the study, 40 patients were included and
subsequently received budesonide (1600mcg daily) during 3 months in the run-in
period. After randomisation they received either combination therapy or
continued the budesonide for another 3 months observation period. 37 patients
completed the study. The observations included HRQL, pulmonary function tests
and microbiologic isolates. The study showed a clinically significant
improvement in HRQL (symptom score domain) in the subgroup using combination
therapy. No change was seen in exacerbations, nor in pulmonary function or
microbiologic cultures. The limitation of this study is the small sample size
and the fact that it was a single centre study. Moreover there was no placebo
control group in the study design, so all patients did receive an inhalation
steroid. The question can be raised that the effect is merely through the LABA
component. In addition the clinical relevant amount of sputum and purulence
were not assessed in this study. In an observational study by Ping Wei et al,
120 patients were assigned to combined inhaled therapy (salmeterol-fluticasone,
Seretide 250 microgram) versus routine therapy. The seretide group showed
significant improvement in clinical symptoms and reduced exacerbation
frequency. There was no improvement of pulmonary function.
Other clinical studies using salbutamol showed an improvement in pulmonary
function in most cases of BE patients. British Thoracic Society guideline for
Non-CF BE suggest that bronchodilator use may be appropriate for patients with
bronchiectasis who have reversible airflow limitation.
The position of single use ICS in the treatment of Non-CF BE is still unclear.
However some authors have claimed beneficial effects of ICS, such as
improvement of the HRQL and a reduction in daily sputum volume. In the study by
Tsang et al, 86 patients were randomized to receive either fluticasone 500
microgram twice daily or matched placebo. The authors only claimed effects on
24 hour sputum volume and exacerbation frequency. No effects were seen on
pulmonary function tests.
However, in all described studies there was no clear exclusion of patients with
Asthma or COPD. To determine the effect of ICS/LABA in BE; these patient groups
have to be excluded, because of the known beneficial effects of ICS/LABA.
The current study will be the first study excluding patients with Asthma and
COPD.
Study objective
Since coughing is the major symptom in BE, the objective of this trial is to
evaluate the clinical efficacy of ICS/LABA treatment in subjects with BE on
coughing. The primary outcome variables of interest is the Leicester cough
questionnaire (LCQ), also we look at the improvement of health related quality
of life (using the QOL-B questionnaire) and exacerbation frequency in a
prospective setting. The use of the LCQ questionnaire in BE has been validated
in other studies.
Study design
A prospective double-blind randomized controlled trial comparing
Formoterol-beclomethasone 12/200 mcg BID versus placebo to evaluate the
reduction in cough measured by the LCQ in patients with BE, excluding asthma
COPD. And for the secondary objective the improvement of health-related
quality of life and on symptoms and pulmonary function (FEV1) and the frequency
of exacerbation requiring an intervention with systemic antibiotics
(oral/intravenous [i.v.]) in subjects with non-CF BE.
Eligible subjects will be randomized to treatment with
formoterol-beclomethasone or matching placebo.
All subjects will be treated with the regimen of medication for 3 months. An
end-of-study (EOS) visit will be performed after completion of the follow-up
period.
Intervention
Formoterol-beclomethasone 12/200 mcg BID versus placebo inhalation dosis
aerosol for a period of 3 months
Study burden and risks
Benefit:
- reduction in coughing and therefore improvement in quality of life
- reduction in exacerbations
Risks:
- experience of Adverse events, like development of hoarseness; oral
candidiasis; tachycardia
All adverse events are reversible after withdrawal of the medication. oral
candidiasis will need topical treatment with good reaction
An inhalation with the medication will last 1 minute
's Gravendijkwal 230
Rotterdam 3015CE
NL
's Gravendijkwal 230
Rotterdam 3015CE
NL
Listed location countries
Age
Inclusion criteria
· Age >= 18 years;
· Symptomatic patient (wheezing, cough and dyspnoea);
· Proven and documented diagnosis of BE by high resolution computed tomography
· Stable pulmonary status as indicated by FEV1 (percent of predicted) >=30%
· Stable clinically phase (ie, subjects free from acute exacerbation for at
least 6 weeks prior to the start of the study);
· Stable regimen of standard treatment if used as chronic treatment for BE, at
least for the past 4 weeks prior to screening. And/or macrolides if used as
chronic treatment for BE at least for the past 6 months prior to screening;
· Coughing on the majority of days.
Exclusion criteria
Possible asthma according to the definition of the Global Initiative for Asthma
(GINA) with:
o Positive bronchodilator reversibility test (increase in FEV1 of >12% and
>200 mL from baseline, 10-15 minutes after 200-400 mcg salbutamol or equivalent)
OR
o Positive bronchial challenge test (fall in FEV1from baseline of >=20% with
standard doses of methacholine or histamine)
- Known intolerance for ICS or LABA.
- Current ICS use
- Other cardiopulmonary conditions (other than bronchiectasis) that could
modify spirometric valeus.
- Women who are pregnant, lactating, or in whom pregnancy cannot be excluded;
- Cigarette smoking history of > 10 pack-years and/or current smokers;
- Expected to die within 72 hours after enrolment
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2017-001665-25-NL |
| CCMO | NL61630.078.18 |