The primary objective is to confirm that bronchodilator monotherapy (tiotropium) plus behavioural modification, bronchodilator combination therapy (tiotropium + olodaterol FDC) plus behavioural modification, and bronchodilator combination therapy (…
Source
Brief title
Condition
- Respiratory disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
No registrations found.
Outcome measures
Primary outcome
The primary endpoint is endurance time [sec] during ESWT to symptom limitation
at walking speed corresponding to 85% of predicted maximum oxygen consumption
(VO2 peak) after 8 weeks of pharmacological treatment and non-pharmacological
intervention.
Secondary outcome
- Average daily walking time measured by the activity monitor in the week prior
to Week 12.
- Average daily walking intensity measured by the activity monitor in the week
prior to Week 12.
- Perceived difficulties as evaluated with FPI-SF total score at Week 12.
- Endurance time during ESWT to symptom limitation at walking speed
corresponding to 85% of predicted maximum oxygen consumption (VO2 peak) after
12 weeks of treatment.
- 1 hour post-dose FEV1, after 8 weeks of treatment.
- 1 hour post-dose FVC, after 8 weeks of treatment.
- Resting IC measured at 1.5 hours post *dose, after 8 weeks of treatment.
Background summary
The COPD treatment guidelines advise treatment with different mechanisms of
action. Short-acting anticholinergics and beta2-agonists in fixed dose
combinations have shown to be effective and safe and are user-friendly to
patients. Once daily fixed dose combinations of long-acting anticholinergs and
beta2-agonists are not yet available. Tiotropium Bromide is a registered once
daily long-acting abticholinergic for the treatment of COPD and will be
combined with once daily long-acting beta2-agonist, olodaterol. It is expected
that the combination of these two once daily bronchodilators with different
mechanisms of action will provide an optimal long term bronchdilation and is
user-friendly.
Important patient-centred goals for both pharmacological and
non-pharmacological therapies in COPD include improving exercise
capacity, easing the performance of daily activities (i.e. reducing exertional
symptoms), and increasing levels of physical activity to minimize or reverse
the longer term adverse effects of a sedentary lifestyle.
A recent study found that physical activity was the best predictor of overall
health status in patients with mild-to-moderate COPD. There is, however, a need
for a multi domain patient reported outcome (PRO) instrument that captures all
relevant dimensions of physical activity, in order to gain a full understanding
of the effects of interventions targeted at improving physical activity.
The PROactive instrument is being developed as a hybrid PRO tool, incorporating
classical items filled out by patients in the evening as well as basic
information retrieved from an activity monitor worn during the day by patients.
Although the design of the instrument is complete, the
scoring and interpretation of the instrument are still being finalized. The
current study along with a set of other international studies will help to
complete the development of the final scoring algorithm and the final
validation.
Study objective
The primary objective is to confirm that bronchodilator monotherapy
(tiotropium) plus behavioural modification, bronchodilator combination therapy
(tiotropium + olodaterol FDC) plus behavioural modification, and bronchodilator
combination therapy (tiotropium + olodaterol FDC) plus exercise training plus
behavioural modification improve exercise capacity as compared to placebo plus
behavioural modification in the study population.
The second objective is to evaluate the effect of the interventions
(pharmacological intervention +/- exercise training, with a comprehensive
behavioural modification program) on two domains of physical activity:
(i) Amount of physical activity (as measured with the activity monitor).
(ii) Perceived difficulties associated with physical activity (as measured by
the FPI-SF questionnaire).
The third objective is to explore the extent to which postulated moderating
variables (motivation, self-efficacy, cognitive function, depression, anxiety,
baseline level of activity, 6MWT distance, BMI, sex, age, waist circumference,
rescue medication use and external and internal barriers) influence the
increase in amount of physical activity and perceived difficulties associated
with physical activity.
The fourth objective is to further validate and test the responsiveness of the
hybrid PROactive instrument (amount of physical activity, perceived
difficulties associated with physical activity).
Study design
All interventions will be administered in conjunction with a behavioural
modification program for patients with chronic obstructive pulmonary disease
(COPD).
After signing Informed Consent and completing an initial screening visit (Visit
1), patients will enter a 4-week screening period to ensure clinical stability
(i.e. no exacerbations). Patients who meet all the inclusion criteria and none
of the exclusion criteria will be randomized at Visit 4 to one of four arms in
which they will receive either:
i. tiotropium + olodaterol (5 *g/5 *g) fixed dose combination inhalation
solution, delivered once daily via the Respimat® Inhaler, with exercise
training and behavioural modification
ii. tiotropium + olodaterol (5 *g/5 *g) fixed dose combination inhalation
solution, delivered once daily via the Respimat® Inhaler, with behavioural
modification
iii. tiotropium (5 *g) inhalation solution, delivered once daily via the
Respimat® Inhaler, with behavioural modification
iv. placebo inhalation solution, delivered once daily via Respimat® Inhaler,
with behavioural modification
Medication treatment in each intervention arm and behavioural modification
intervention will be administered for 12 weeks while supervised exercise
training in the first treatment arm will be given for 8 weeks. Exercise
capacity and physical activity will be assessed during weeks when patients will
have completed supervised exercise training and while continuing to take study
medication.
A follow-up visit (Visit 9) will be scheduled three weeks after the last dose
of study medication or, in case of early discontinuation, 3 weeks after the
last dose of study medication.
Intervention
Bronchodilator therapy; during twelve weeks a once daily inhalation of
studymedication with the Respimat® Inhaler with one of the following
treatments:
1. tiotropium + olodaterol (5 *g/5 *g) fixed dose combination inhalation
solution
2. tiotropium (5 *g) inhalation solution
3. placebo inhalation solution
Patients will also undergo/ need to:
- Behavioural modification (group) sessions
- An exercise training program (pulmonay rehabilitation) of 8 weeks duration to
improve exercise tolerance
- Spirometry
- (Shuttle) walk tests
- Laboratory tests
- completing an eDiary every night
- completing several different patient questionnaires during study visits
Study burden and risks
During the course of the study, each patient will need to perform spirometry
measurments (6 times). In principle, no serious risks are involved in
spirometry. Nevertheless, risks and discomforts associated with lungfunction
testion may include shortness of breath, dizziness or headache during the
breathing tests. Should this occur, the patient may receive treatment.
All patients will perform an exercise capacity assessment, using the endurance
shuttle walk test (ESWT) and 6-minute walk test. Maximal exercise capacity will
be determined during an incremental walk test (ISWT). Patients randomised in
arm 1, will need to follow a pulmonary rehabililtation (exercise) programme for
8 weeks (three times a week, 1.5 hours per session). Walk tests and pulmonary
rehabiliation exercises could provoke significant symtoms like sudden chest
pain, loss of coordination, mental confusion or extreme shortness of breath.
Changes may also be seen on the finger clip placed on patients to monitor the
amount of oxygen in the patients blood. The walk tests or exercise training
will be stopped if such signs or symptoms occur. All assessments will be
continously monitored by qualified study staff and safety monitoring will be
performed. The study doctor will exclude any person who might not tolerate
exercise testing.
Three times during the study (or if necesarry four times), a physical
examination will be performed. Patients will be asked to complete
questionnaires. In addition, patients will be asked to complete an electronic
diary every night before they go to sleep. The use of rescue medication will
also be recorded in the diary.
Patients will be asked to ware a physical activity monitor during the time they
are awake for 3 periods (1 week each).
All patients will need to join 4 group Behaviroual Modification (BM) sessions
and 2 individual BM sessions.
During the screening period previous medications will be washed-out. For this
reason, all patients will receive Ventolin as rescue medication at start of
screening period an may also used during the treatment period. Besides that,
Atrovent may be used during screening period. Oral and inhaled corticosteroids
are also accepted throughout the study. There are also some restrictions
regarding physical activities performed in the period before each visit.
Inhalation of study medication may cause side effects. Normally these side
effects are mild and they usually dissapear with continued treatment. Safety
monitoring include bloodsampling, measurement of vital signs and ECG
monitoring. Bloodsampling may also cause some incovenience.
Comeniusstraat 6
Alkmaar 1817 MS
NL
Comeniusstraat 6
Alkmaar 1817 MS
NL
Listed location countries
Age
Inclusion criteria
- All patients must sign an informed consent consistent with ICH-GCP guidelines prior to participation in the trial, which includes medication washout and restrictions.;- All patients must have a diagnosis of chronic obstructive pulmonary disease and must meet the following spirometric criteria:;Patients must have relatively stable airway obstruction with a post-bronchodilator 30% <= forced expiratory volume in one second <80% of predicted normal; Global Initiative for Chronic Obstructive Lung DiseaseGlobal stage II - III, and a post-bronchodilator Tiffeneau index <70% at Visit 1.;- Male or female patients, aged <= 40 years and <= 75 years.;- Patients must be current or ex-smokers with a smoking history of more than 10 pack years (see Appendix 10.3 for calculations). Patients who have never smoked cigarettes must be excluded.
Exclusion criteria
- Patients with a significant disease other than chronic obstructive pulmonary disease.;- Patients with clinically relevant abnormal baseline haematology, blood chemistry, or urinalysis.;- Patients with a history of asthma.;- A diagnosis of thyrotoxicosis.;- A diagnosis of paroxysmal tachycardia (>100 beats per minute).;- A history of myocardial infarction within 1 year of screening visit.;- Unstable or life-threatening cardiac arrhythmia.;- Hospitalized for heart failure within the past year.;- Known active tuberculosis.;- A malignancy for which patient has undergone resection, radiation therapy or chemotherapy within last five years.;- A history of life-threatening pulmonary obstruction and patients with chronic respiratory failure.;- A history of cystic fibrosis.;- Clinically evident bronchiectasis.;- A history of significant alcohol or drug abuse.;- Any contraindications for exercise testing.;- Patients who have undergone thoracotomy with pulmonary resection.;- Patients being treated with any oral ß-adrenergics.;- Patients being treated with oral corticosteroid medication at unstable doses (i.e., less than six weeks on a stable dose) or at doses in excess of the equivalent of 10 mg of prednisone per day or 20 mg every other day.;- Patients who regularly use daytime oxygen therapy for more than one hour per day and in the investigators opinion will be unable to abstain from the use of oxygen therapy during clinic visits.;- Patients who have completed a pulmonary rehabilitation program in the six weeks prior to the screening visit or patients who are currently in a pulmonary rehabilitation program.;- Patients who have a limitation of exercise performance as a result of factors other than fatigue or exertional dyspnoea, such as arthritis in the leg, angina pectoris or claudication or morbid obesity.;- Patients who have taken an investigational drug within one month or six half lives (whichever is greater) prior to screening visit.;- Patients with known hypersensitivity to ß-adrenergics drugs, anticholinergic drugs, benzalkonium chloride, disodium edentat, or any other component of the Respimat® inhalation solution delivery system.;- Pregnant or nursing women.;- Women of childbearing potential not using highly effective methods of birth control.;- Patients who have previously been randomized in this study or are currently participating in another study.
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 | EUCTR2013-002671-18-NL |
CCMO | NL46956.015.14 |
Other | nog niet bekend |