Chronic Obstructive Airway DiseasePhase 4BOTHNCT03275116
The Effect of Twice Daily vs. Once Daily Bronchodilation on Hyperinflation in COPD Patients During 24 Hours.
A Phase 4 study testing Tiotropium 'Respimat' 5 mcg and Aclidinium Bromide/Formoterol Fumarate 340/12 mcg in people with Chronic Obstructive Airway Disease, run by Maastricht University Medical Center at 1 site in Netherlands.
Trial summary
To study the effect of twice daily dual bronchodilation versus once daily single bronchodilation in patients with chronic obstructive pulmonary disease on 24-hour static and dynamic hyperinflation. Read more about this study
- Who is it for?
- Ages 40 years and older
- Conditions the study is for
- Chronic Obstructive Airway Disease
- What is being tested?
- Tiotropium 'Respimat' 5 mcg and Aclidinium Bromide/Formoterol Fumarate 340/12 mcg
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 49 participants
- Where
- 1 siteNetherlands
- Study dates
- 7 Jul 2017to Dec 2020
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male and female adults (with an equal sex ratio not exceeding 35-65%) aged ≥ 40 years with written informed consent obtained prior to any study-related procedure.
- Patients entering pulmonary rehabilitation at CIRO.
- Patients with a diagnosis of moderate to very severe COPD at least 12 months before the screening visit (A post-bronchodilator FEV1 < 80% of the predicted normal value and a post-bronchodilator FEV1/FVC < 0.7 at least 10-15 min after 4 puffs (4 x 100 μg) of salbutamol)
- Patients with severe static hyperinflation defined as residual volume (body box) > 150 % predicted.
- Current smokers or ex-smokers with a smoking history of at least 10 pack years [pack-years = (number of cigarettes per day x number of years)/20].
- MMRC (modified Medical Research Council Dyspnea scale) score ≥ 2.
- A cooperative attitude and ability to use correctly the inhalers. ICS (inhalation corticosteroids) use is not an exclusion criterion for participation in the study and will be continued during the study. During the study, patients receive fluticasone in an equivalent dose of their own regimen.
- The use of neomacrolides and/or leukotriene antagonists is not an exclusion criterion for participation in the study and will be continued in the study, as long as there are no changes in the regiments in the 4 weeks prior to the study. Also, the use of corticosteroid maintenance therapy is allowed, provided that no changes in the regiments took place in the 4 weeks prior to study.
Who cannot join
- Pregnant or lactating women and all women physiologically capable of becoming pregnant (i.e. women of childbearing potential)
- Patients requiring use of the following medications:
- A course of systemic steroids longer than 3 days for COPD exacerbation in the 4 weeks prior to screening.
- A course of antibiotics for COPD exacerbation longer than 7 days in the 4 weeks prior to screening. NB; maintenance treatment of macrolides is allowed, without any changes in the regimen in the 4 weeks prior to the study.
- PDE4 (phosphodiesterase-4) inhibitors in the 4 weeks prior to screening.
- Xanthines in the 4 weeks prior to screening.
Show all 29Show fewer
- Use of antibiotics for a lower respiratory tract infection (e.g pneumonia) in the 4 weeks prior to screening.
- COPD exacerbation requiring prescriptions of systemic corticosteroids and/or antibiotics or hospitalization during the run-in period.
- Patients treated with non-cardio selective β-blockers in the month preceding the screening visit or during the run-in period. Those patients may enter the study after non-selective β-blockers withdrawal and/or cardio selective β-blockers intake for at least 10 days before the first study day.
- Patients treated with long-acting antihistamines unless taken at stable regimen at least 2 months prior to screening and to be maintained constant during the study, or if taken as PRN (Pro Re Nata).
- Patients requiring long term (at least 12 hours daily) oxygen therapy for chronic hypoxemia.
- Known respiratory disorders other than COPD which may impact the efficacy of the study drug according the investigator's judgment. This can include but is not limited to alpha-1 antitrypsin deficiency, active tuberculosis, a history of asthma, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension and interstitial lung disease.
- Previous lung surgery or endoscopic lung volume reduction interventions.
- Patients who have clinically significant cardiovascular condition such as, but not limited to, unstable ischemic heart disease, NYHA Class III/IV left ventricular failure, acute ischemic heart disease in the last year prior to study screening, history of sustained cardiac arrhythmias or sustained and non-sustained cardiac arrhythmias diagnosed in the last 6 months (sustained means lasting more than 30 seconds and or ending only with external action, and or leads to hemodynamic collapse; non-sustained means > 3 beats < 30 seconds, and or ending spontaneously, and or asymptomatic), impulse conduction high degree blocks, patients with Implantable Cardioverter Defribrillator (ICD).
- Patients with atrial fibrillation (AF):
- Paroxysmal Atrial Fibrillation
- Persistent: AF episode either lasts longer than 7 days or requires termination by cardioversion, either with drugs or by direct current cardioversion (DCC) within 6 months from screening.
- Long standing persistent as defined by continuous atrial fibrillation diagnosed for less than 6 months with or without a rhythm control strategy.
- Permanent: for at least 6 months with a resting ventricular rate ≥ 100/min controlled with a rate control strategy (i.e., selective β-blocker, calcium channel blocker, pacemaker placement, digoxin or ablation therapy).
- An abnormal and clinically significant 12-lead ECG which may impact the safety of the patient according to investigator's judgement. Patients whose electrocardiogram (ECG12 lead) shows QTcF >450 ms for males or QTcF >470 ms for females at screening visit are not eligible (not applicable for patient with pacemaker).
- Medical diagnosis of narrow-angle glaucoma, prostatic hypertrophy or bladder neck obstruction that in the opinion of the investigator would prevent use of anticholinergic agents.
- History of hypersensitivity to anticholinergics, β2-agonist or any of the excipients contained in any of the formulations used in the trial which may raise contra-indications or impact the efficacy of the study drug according to the investigator's judgement.
- Clinically significant laboratory abnormalities indicating a significant or unstable concomitant disease which may impact the efficacy or the safety of the study drug according to investigator's judgement.
- Patients with hypokalaemia (serum potassium levels <3.5 mEq/L (or 3.5 mmol/L)) or uncontrolled hyperkalaemia according to investigator's judgment.
- Unstable concurrent disease: e.g. uncontrolled hyperthyroidism, uncontrolled diabetes mellitus or other endocrine disease; significant hepatic impairment; significant renal impairment; uncontrolled gastrointestinal disease (e.g. active peptic ulcer); uncontrolled neurological disease; uncontrolled haematological disease; uncontrolled autoimmune disorders, or other which may impact the efficacy or the safety of the study drug according to investigator's judgment.
- Patients with any history of malignancy likely to result in significant disability or likely to require significant medical or surgical intervention within the next six months (after V1) or with malignancy for which they are currently undergoing radiation therapy or chemotherapy.
- History of alcohol abuse and/or substance/drug abuse within 12 months prior to screening visit.
- Participation in another clinical trial where investigation drug was received less than 8 weeks prior to screening visit.
- Patients with hypercapnia (≥6.5 kPa) in the arterial blood gas. At screening visit (V1), all exclusion criteria will be checked.
Trial locations and contacts
1 site in 1 country.
Netherlands1 site, 1 recruiting
- Recruiting
Ciro, center of expertise in chronic organ failure
Horn, 6085NM
Maud Koopman, MD, +31475587653, maudkoopman@ciro-horn.nl
About this study
Official title: The Effect of Twice Daily Aclidinium Bromide/Formoterol Fumarate 340/12 mcg vs. Once Daily Tiotropium 'Respimat' 5mcg on Static and Dynamic Hyperinflation in Patients With COPD During 24 Hours
To study the effect of twice daily dual bronchodilation versus once daily single bronchodilation in patients with chronic obstructive pulmonary disease on 24-hour static and dynamic hyperinflation.
Read the detailed description
To study the effect of twice daily dual bronchodilation (Aclidinium Bromide/Formoterol Fumarate 340/12 mcg) versus once daily single bronchodilation (Tiotropium 'respimat' 5 mcg) in patients with COPD on 24-hour static and dynamic hyperinflation, spirometry respiratory symptoms and sleep quality.
- Conditions
- Chronic Obstructive Airway Disease
- Being tested
- Tiotropium 'Respimat' 5 mcg, Aclidinium Bromide/Formoterol Fumarate 340/12 mcg
- Keywords
- Bronchodilation, Hyperinflation, Physical activity, Sleep quality
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive, Motor Activity, Sleep Initiation and Maintenance Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tiotropium 'Respimat' 5 mcgDrug
Also called Spiriva 'Respimat'
Once daily single bronchodilation
Aclidinium Bromide/Formoterol Fumarate 340/12 mcgDrug
Also called Duaklir Genuair
Twice daily dual bronchodilation
| Study group | Role | What they receive |
|---|---|---|
| Twice daily dual bronchodilation | Active comparator | Twice daily Aclidinium Bromide/Formoterol Fumarate 340/12 mcg during 4 days Receives: Drug: Tiotropium 'Respimat' 5 mcg |
| Once daily single bronchodilation | Active comparator | Once daily Tiotropium 'Respimat' 5 mcg during 4 days Receives: Drug: Aclidinium Bromide/Formoterol Fumarate 340/12 mcg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Static hyperinflation
Residual volume (RV) measured by repeated body box measurements
Measured: 24 hours
Secondary outcomes (9)
Dynamic hyperinflation
∆ICMPT (inspiratory capacity, measured by metronome paced tachypnea)
Measured: 24 hours
Airway obstruction
Measured by FEV1 (forced expiratory capacity in 1 second) by repeated spirometry
Measured: 24 hours
Forced vital capacity
Measured by FVC (forced vital capacity) by repeated spirometry
Measured: 24 hours
Inspiratory vital capacity
Measured by IVC (inspiratory vital capacity) by repeated spirometry
Measured: 24 hours
Momentarily symptoms of dyspnea
Momentarily symptoms of dyspnea during 24 hours will be measured by the BORG scale on dyspnea.
Measured: 24 hours
Respiratory symptoms
Dyspnea throughout the week will be measured by the Baseline Dyspnea Index and the Transition Dyspnea Index
Measured: 4 days
Night-time awakenings due to respiratory symptoms
Quality of sleep will be measured using night-time awakening scores, counting the night-time awakenings due to COPD symptoms (wheezing, shortness of breath and coughing). Also a VAS score for sleep quality will be used. A visual score in which patients will assign a number from 0-10 on the question: "How did you sleep the last few days?". In wich 0 is "couldn't be worse" and 10 is "couldn't be better".
Measured: 4 days
Sleep quality
A visual score in which patients will assign a number from 0-10 on the question: "How did you sleep the last few days?". In wich 0 is "couldn't be worse" and 10 is "couldn't be better".
Measured: 4 days
Nighttime physical activity
Measured by an accelerometer, as inverse surrogate for sleep quality
Measured: 4 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Sep 2017
- Study start7 Jul 2017
- Primary completionApr 2020 (estimated)
- Study completionDec 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Obstructive Airway DiseaseStudies of the same condition, open and under way.
- More trials run by Maastricht University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 49 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Maastricht University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Center for Integrated Rehabilitation and Organ Failure Horn, AstraZeneca
- Responsible party
- Sponsor
- Investigators
- Lowie Vanfleteren, MD, PhD, Principal investigator, CIRO, centre of expertise for chronic organ failure
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03275116
- Sponsor's protocol ID
- 59452
- Acronym
- BOTH
- Status last verified
- Mar 2020
- First submitted
- 8 Nov 2016
- Last updated
- 10 Mar 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Twice Daily Aclidinium Bromide/Formoterol Fumarate 340/12 mcg vs. Once Daily Tiotropium 'Respimat' 5mcg on Static and Dynamic Hyperinflation in Patients With COPD During 24 Hours
- ClinicalTrials.gov ID
- NCT03275116
- Acronym / sponsor ID
- BOTH / 59452
- Conditions
- Chronic Obstructive Airway Disease
- Keywords
- Bronchodilation, Hyperinflation, Physical activity, Sleep quality
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 49 participants (estimated)
- Lead sponsor
- Maastricht University Medical CenterUniversity, hospital or other
- Collaborators
- Center for Integrated Rehabilitation and Organ Failure Horn, AstraZeneca
- Study start
- 7 Jul 2017 (actual)
- Primary completion
- Apr 2020 (estimated)
- Study completion
- Dec 2020 (estimated)
- First posted
- 7 Sep 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To study the effect of twice daily dual bronchodilation versus once daily single bronchodilation in patients with chronic obstructive pulmonary disease on 24-hour static and dynamic hyperinflation.
Detailed description
To study the effect of twice daily dual bronchodilation (Aclidinium Bromide/Formoterol Fumarate 340/12 mcg) versus once daily single bronchodilation (Tiotropium 'respimat' 5 mcg) in patients with COPD on 24-hour static and dynamic hyperinflation, spirometry respiratory symptoms and sleep quality.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Twice daily dual bronchodilation | Active comparator | Drug: Tiotropium 'Respimat' 5 mcgTwice daily Aclidinium Bromide/Formoterol Fumarate 340/12 mcg during 4 days |
| Once daily single bronchodilation | Active comparator | Drug: Aclidinium Bromide/Formoterol Fumarate 340/12 mcgOnce daily Tiotropium 'Respimat' 5 mcg during 4 days |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Male and female adults (with an equal sex ratio not exceeding 35-65%) aged ≥ 40 years with written informed consent obtained prior to any study-related procedure.
- Patients entering pulmonary rehabilitation at CIRO.
- Patients with a diagnosis of moderate to very severe COPD at least 12 months before the screening visit (A post-bronchodilator FEV1 < 80% of the predicted normal value and a post-bronchodilator FEV1/FVC < 0.7 at least 10-15 min after 4 puffs (4 x 100 μg) of salbutamol)
- Patients with severe static hyperinflation defined as residual volume (body box) > 150 % predicted.
- Current smokers or ex-smokers with a smoking history of at least 10 pack years [pack-years = (number of cigarettes per day x number of years)/20].
Key exclusion criteria (29 listed)
- Pregnant or lactating women and all women physiologically capable of becoming pregnant (i.e. women of childbearing potential)
- Patients requiring use of the following medications:
- COPD exacerbation requiring prescriptions of systemic corticosteroids and/or antibiotics or hospitalization during the run-in period.
- Patients treated with non-cardio selective β-blockers in the month preceding the screening visit or during the run-in period. Those patients may enter the study after non-selective β-blockers withdrawal and/or cardio selective β-blockers intake for at least 10 days before the first study day.
- Patients treated with long-acting antihistamines unless taken at stable regimen at least 2 months prior to screening and to be maintained constant during the study, or if taken as PRN (Pro Re Nata).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tiotropium 'Respimat' 5 mcgAlso: Spiriva 'Respimat'Once daily single bronchodilation | Drug | Twice daily dual bronchodilation |
| Aclidinium Bromide/Formoterol Fumarate 340/12 mcgAlso: Duaklir GenuairTwice daily dual bronchodilation | Drug | Once daily single bronchodilation |
Primary outcome
Static hyperinflation
Time frame: 24 hours
Residual volume (RV) measured by repeated body box measurements
9 secondary outcomes
Dynamic hyperinflation
Time frame: 24 hours
Airway obstruction
Time frame: 24 hours
Forced vital capacity
Time frame: 24 hours
Inspiratory vital capacity
Time frame: 24 hours
Momentarily symptoms of dyspnea
Time frame: 24 hours
Respiratory symptoms
Time frame: 4 days
Night-time awakenings due to respiratory symptoms
Time frame: 4 days
Sleep quality
Time frame: 4 days
Nighttime physical activity
Time frame: 4 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Mar 2020.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lowie Vanfleteren, MD, PhD principal investigator
CIRO, centre of expertise for chronic organ failure
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Tiotropium 'Respimat' 5 mcg and Aclidinium Bromide/Formoterol Fumarate 340/12 mcg in people with Chronic Obstructive Airway Disease, run by Maastricht University Medical Center at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 10 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Lowie Vanfleteren, MD, PhD (+31475587644, lowievanfleteren@ciro-horn.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Static hyperinflation (time frame: 24 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Mar 2020.