Chronic Obstructive Pulmonary DiseasePhase 4ANDA2NCT01656005
Beta Blocker Therapy in Moderate to Severe COPD
A Phase 4 study testing Carvedilol, Bisoprolol and Beclometasone/formoterol in people with Chronic Obstructive Pulmonary Disease, run by University of Dundee at 1 site in United Kingdom.
Trial summary
Beta blockers are a type of medication mainly used for heart disease. They are commonly used to treat 'angina' and to prevent heart attacks. Patients with COPD are more likely to suffer from heart disease and so already benefit from this treatment for this reason. Read more about this study
- Who is it for?
- Ages 40 to 80 years
- Conditions the study is for
- Chronic Obstructive Pulmonary Disease
- What is being tested?
- Carvedilol, Bisoprolol and Beclometasone/formoterol
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Aug 2012to Jul 2016
- 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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Moderate to severe COPD (GOLD stage 2 and 3)
- FEV1 30-80% predicted
- No exacerbation in previous 3 months
- Smoking history ≥ 10 pack years
- Oxygen saturations≥ 92% on room air at rest
- ECG demonstrating sinus rhythm
Who cannot join
- Use of domiciliary oxygen
- History of other primary obstructive lung disease including asthma or bronchiectasis
- History of unstable angina, uncontrolled hypertension or heart failure NYHA class 3-4
- Overt clinical signs of right heart failure
- Average resting systolic BP<110mmHg
- Average resting HR<60bpm
Show all 13Show fewer
- Pregnancy or lactation
- Known or suspected sensitivity to/intolerance of investigational medicinal product
- Inability to comply with compulsory aspects of protocol
- Any degree of heart block
- Concomitant prescription of beta-blockers, rate-limiting calcium channel blockers, digoxin or amiodarone
- Any clinically significant medical condition that may endanger the health or safety of the participant, or jeopardise the protocol
- Participation in another trial within the previous 30 days
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Asthma and Allergy Research Group, Ninewells Hospital and Medical School, University of Dundee
Dundee, DD1 9SY
About this study
Official title: Evaluation of Effects of Chronic Dose Exposure to Cardioselective and Non-cardioselective Beta Blockers on Measures of Cardiopulmonary Function in Moderate to Severe COPD.
Beta blockers are a type of medication mainly used for heart disease. They are commonly used to treat 'angina' and to prevent heart attacks. Patients with COPD are more likely to suffer from heart disease and so already benefit from this treatment for this reason. In addition to this, new research suggests that there may be further benefit of using beta blockers for COPD, even without also having heart disease.
The reason why beta blockers are not widely used in COPD at present is because of their potential to make symptoms of COPD worse by causing the airways to narrow. Beta blockers are the opposite type of medication to 'beta-agonists' such as salbutamol which you may be taking for symptoms of breathlessness or wheezing. Nevertheless beta blockers are still used in COPD where the benefits (for example heart disease) outweigh any risks.
Read more
Current COPD treatment includes inhaled steroids and long acting beta agonists, often given in a combination inhaler (e.g. Seretide or Symbicort) to treat both airway inflammation and airway narrowing, leading to improvement in symptoms. Another drug commonly used is Tiotropium (Spiriva) which is another type of long acting inhaler medication to help with widening the airways.
In this study, we wish to find out if two different types of beta blocker cause different effects on the airways in COPD patients. One type of beta blocker is more 'selective' in acting mainly on the heart, with the other type having more general or 'non-selective' effects on both the heart and lungs. By doing this we will also be able to look at how the beta blockers work alongside the 'usual' inhaler treatment described above.
Read the detailed description
Screening Visit A member of the research team will discuss the Patient Information Sheet with the participant, answer any questions posed and written informed consent will be obtained.
Prior to screen participants will be asked to withhold tiotropium for 48 hours ipratropium bromide for 12 hours and salbutamol for 6 hours.
A general physical examination will be carried out by a qualified medical practitioner.
A pregnancy test from a urine sample will be performed for all female participants with advice issued to both male and female participants to use contraception throughout the duration of the study.
The following will be measured:
Spirometry with sequential reversibility to 400μg salbutamol then 80 μg ipratropium bromide according to American Thoracic Society guidelines Resting Electrocardiogram Whole body plethysmography (where possible) Impulse Oscillometry
Oxygen saturations breathing room air after 5 mins rest Heart rate and blood pressure. 6 Minute Walk Test (if physically able)
Inhaler technique will be assessed and confirmed adequate.
Full blood count, renal function, electrolytes, liver enzymes and random blood glucose will be measured.
Participants will be checked against all inclusion and exclusion criteria. Those found to be eligible will proceed to the run-in period.
Run-in period Participants who are taking inhaled corticosteroids, combination inhalers, Long acting bata agonists or long-acting anti-muscarinics will have these discontinued.
All participants entering the run-in period will be commenced on Fostair (Beclometasone/Formoterol) 100/6, 2 puffs twice daily via spacer device for approximately 2 weeks.
Participants will be given a PiKO monitor to record domiciliary Forced expiratory volume1 and Forced expiratory Volume6 twice daily (approximately 12 hours apart) in a diary supplied by the department as well as domiciliary oxygen saturation and Heart Rate monitor to be recorded twice daily. They will also complete a daily diary of reliever use and symptoms. These will all be performed from the beginning of the run-in period to the end of the study.
At the end of run-in, participants will be again checked against all inclusion and exclusion criteria and the hief Investigator or medical investigator for the study will sign the declaration on the Case Report Form, to confirm the subject's suitability to receive the study drug according to study protocol. Those eligible will proceed to study visit 1. Those who do not fulfil the study criteria will be returned to their pre-study medication and their GP informed of any medically relevant data.
Study Visit 1 (Baseline 1) Participants will attend the department on the morning of their study visit.
Participants will be asked to withhold their ipratropium for 12 hours and salbutamol for 6 hours prior to visit.
Diaries of symptoms, reliever use and domiciliary FEV1 will be reviewed.
Baseline measurements to be recorded are:
IOS Slow Vital Capacity Spirometry Resting ECG Resting O2 sats HR and BP St George's Respiratory Questionnaire 6MWT (where physically possible and only if performed at screen) Echocardiogram (where technically possible) Serum (after at least 30mins supine posture): Aldosterone, Angiotensin II, BDNF, BNP, Potassium
Provided average HR>60bpm and average systolic BP>110mmHg the participant will be randomised to 1 of 2 beta-blocker treatments comprising:
- Carvedilol: 1 week of 3.125mg bid, 1 week of 6.25mg bid, 4 weeks of 12.5mg bid or
- Bisoprolol: 1 week of 1.25mg od, 1 week of 2.5mg od, 4 weeks of 5mg od
Participants will be given their first 4 weeks of randomised IMP for the treatment period at this study visit.
When titrating their beta-blocker at home, should the participant start to experience side-effects related to beta-blocker therapy or they find that their HR is dropping below 55bpm they will be informed to phone the department working hours) or the emergency mobile number (out of hours).
Participants will be allowed to complete each treatment arm on their maximum tolerated dose of beta-blocker, should this be less than the maximum prescribed dose.
Participants in both treatment arms will continue taking Fostair 100/6, 2 puffs bid via spacer device for the first 5 weeks of each treatment period. For the final (6th) week of each treatment period they will receive inhaled beclometasone dipropionate (as Clenil) 200μg, 2 puffs bid via spacer device, instead of Fostair.
Participants in both treatment arms will be given Tiotropium 18μg (via handihaler) od for the first 4 weeks of each treatment period. Tiotropium will then be discontinued for the final 2 weeks of each treatment period.
Participants will be given a salbutamol inhaler to use as initial reliever therapy along with an ipratropium inhaler second line on a PRN basis.
The IMPs will be issued to the participant by a member of the research team delegated the task. The allocation will be checked and countersigned by a second delegated member of staff.
Inhaler technique for the different devices will be checked.
A participant instruction and appointment leaflet will be issued and discussed fully with the participant and any questions answered. It will detail:
Emergency contact numbers Instructions on how to take heart rate and O2 sats measurements How to perform domiciliary FEV1 and FEV6 How to write in the diary Potential side effects of study drugs Recording of AEs and concomitant medication use Withholding times for relievers Titration/Discontinuation times for IMPs
Reminders to return medication and bottles at each visit
Study visit 2
Measurements to be recorded at this visit are:
IOS Slow VC Spirometry Resting O2 sats HR and BP (as previously described in 3.5.5) Resting ECG 6MWT (where physically possible and only if performed previously in study) SGRQ
Participants will be given their final 2 weeks of randomised IMP (at their maximum tolerated dose) for that treatment period.
Participants will discontinue their tiotropium for the remaining 2 weeks of the treatment period at this study visit.
Study visit 3
. As for study visit 2 with the addition of Serum BDNF, Potassium
Participants will discontinue their Fostair inhaler at this study visit and be given Clenil (beclometasone) 200ug, 2 puffs bid to take instead for the final week of the treatment period.
Study visit 4 As before plus, Echocardiogram (where technically possible) Serum (after at least 30mins supine posture): Aldosterone, Angiotensin II, BDNF, BNP, Potassium
Participants will finish treatment period 1 at this point and enter a 2 week period of washout (of beta-blocker) prior to crossing over to the other treatment arm.
Participants will discontinue their Clenil and beta-blocker and return to taking Fostair 100/6, 2 puffs bid for the 2 week washout period.
Study Visit 5 (Baseline 2)
Measurements to be recorded are:
IOS Slow VC Spirometry Resting ECG Resting O2 sats HR and BP (as previously described in 3.5.5) SGRQ 6MWT (where physically possible and only if performed at screen) Serum (after at least 30mins supine posture): Aldosterone, Angiotensin II, BDNF, BNP, Potassium
Provided average HR>60bpm and average systolic BP>110mmHg the participant will be crossed over to the beta-blocker treatment that they have not yet received (based on original randomisation) comprising:
- Carvedilol: 1 week of 3.125mg bid, 1 week of 6.25mg bid, 4 weeks of 12.5mg bid
- Bisoprolol: 1 week of 1.25mg od, 1 week of 2.5mg od, 4 weeks of 5mg od Measurements will be repeated as per Study Visit 1.
Study Visits 6 \& 7 Visit 6 will be the same as visit 2 Visit 7 will be the same as visit 3 Study Visit 8
Measurements to be recorded are:
IOS Slow VC Spirometry Resting ECG Resting O2 sats HR and BP (as previously described in 3.5.5) SGRQ 6MWT (where physically possible and only if performed at screen) Echocardiogram (where technically possible) Serum (after at least 30mins supine posture): Aldosterone, Angiotensin II, BDNF, BNP, Potassium
Participants will finish treatment period 2, and, therefore, the study at this point. They will be returned to their usual prescribed medication.
End of Study Period. The study will be complete when the last enrolled participant completes the last visit
- Conditions
- Chronic Obstructive Pulmonary Disease
- Being tested
- Carvedilol, Bisoprolol, Beclometasone/formoterol, Tiotropium, Beclometasone
- Keywords
- COPD, Beta blockers, Cardioselective, Non-cardioselective, Impulse oscillometry
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CarvedilolDrug
Dose titration: 3.125mg bid for 1 week, 6.25mg bid for 1 week, 12.5mg bid for 4 weeks.
BisoprololDrug
Dose titration: 1.25mg od for 1 week, 2.5mg od for 1 week, 5mg for 4 weeks.
Beclometasone/formoterolDrug
Also called Fostair 100/6
2 puffs bid for first 5 weeks in each treatment arm
TiotropiumDrug
Also called Spiriva 18mcg
1 puff daily for first 4 weeks of each treatment arm
BeclometasoneDrug
Also called Clenil 200
2 puffs bid for final week (week 6) of each treatment arm
| Study group | Role | What they receive |
|---|---|---|
| Carvedilol | Experimental | Beclometasone/Formoterol Beclometasone Tiotropium Receives: Drug: Carvedilol; Drug: Beclometasone/formoterol; Drug: Tiotropium; Drug: Beclometasone |
| Bisoprolol | Active comparator | Beclometasone/Formoterol Beclometasone Tiotropium Receives: Drug: Bisoprolol; Drug: Beclometasone/formoterol; Drug: Tiotropium; Drug: Beclometasone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in airway resistance at 5HZ (R5) using impulse oscillometry from baseline.
Measured: 4, 5 and 6 weeks of each treatment period
Secondary outcomes (6)
Change in remaining impulse oscillometry measurements from baseline
Resistance at 20Hz (R20); Reactance at 5Hz (X5); Area under reactance curve (Ax); Resonant frequency (Fres).
Measured: 4, 5 and 6 weeks of each treatment period
Change in spirometry measurements from baseline
Forced expiratory volume in 1 sec (FEV1); Forced vital capacity (FVC); Slow vital capacity; Forced expiratory flow between 25-75% of FVC (FEF25-75)
Measured: 4, 5 and 6 weeks of each treatment period
Change in echocardiogram parameters from baseline
Left ventricular function, right ventricular function, pulmonary pressure, pulmonary acceleration time.
Measured: At 6 weeks of each treatment period
Change in vital signs from baseline
Resting oxygen saturations, heart rate, office blood pressure,
Measured: 4, 5, and 6 weeks in each treatment period
Change in six minute walk test distance from baseline
Measured: 4, 5 and 6 weeks of each treatment periods.
Change in St George's Respiratory Questionnaire score from baseline
Measured: 4, 5 and 6 weeks in each treatment arm
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Aug 2012 (estimated)
- Study startAug 2012
- Primary completionJul 2016
- Study completionJul 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Chronic Obstructive Pulmonary DiseaseStudies of the same condition, open and under way.
- 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
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Dundee
- Sponsor type
- University, hospital or other
- Collaborators
- Tenovus Scotland
- Responsible party
- Sponsor
- Investigators
- William J Anderson, MBChB, Principal investigator, University of DundeeBrian J Lipworth, MD, Study director, University of Dundee
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01656005
- Sponsor's protocol ID
- ANDA2
- Other IDs
- 2011-006008-11
- Acronym
- ANDA2
- Status last verified
- Apr 2019
- First submitted
- 31 Jul 2012
- Last updated
- 23 Apr 2019
- Results posted
- No
- Data monitoring committee
- No
Publications
Jabbal S, Anderson W, Short P, Morrison A, Manoharan A, Lipworth BJ. Cardiopulmonary interactions with beta-blockers and inhaled therapy in COPD. QJM. 2017 Dec 1;110(12):785-792. doi: 10.1093/qjmed/hcx155.
PubMed 29025008
Study at a glance
From the registry record, last updated by the sponsor on 23 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Effects of Chronic Dose Exposure to Cardioselective and Non-cardioselective Beta Blockers on Measures of Cardiopulmonary Function in Moderate to Severe COPD.
- ClinicalTrials.gov ID
- NCT01656005
- Acronym / sponsor ID
- ANDA2 / ANDA2
- Conditions
- Chronic Obstructive Pulmonary Disease
- Keywords
- COPD, Beta blockers, Cardioselective, Non-cardioselective, Impulse oscillometry
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- University of DundeeUniversity, hospital or other
- Collaborators
- Tenovus Scotland
- Study start
- Aug 2012
- Primary completion
- Jul 2016 (actual)
- Study completion
- Jul 2016 (actual)
- First posted
- 2 Aug 2012 (estimated)
- 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.
Beta blockers are a type of medication mainly used for heart disease. They are commonly used to treat 'angina' and to prevent heart attacks. Patients with COPD are more likely to suffer from heart disease and so already benefit from this treatment for this reason. In addition to this, new research suggests that there may be further benefit of using beta blockers for COPD, even without also having heart disease.
The reason why beta blockers are not widely used in COPD at present is because of their potential to make symptoms of COPD worse by causing the airways to narrow. Beta blockers are the opposite type of medication to 'beta-agonists' such as salbutamol which you may be taking for symptoms of breathlessness or wheezing. Nevertheless beta blockers are still used in COPD where the benefits (for example heart disease) outweigh any risks.
Current COPD treatment includes inhaled steroids and long acting beta agonists, often given in a combination inhaler (e.g. Seretide or Symbicort) to treat both airway inflammation and airway narrowing, leading to improvement in symptoms. Another drug commonly used is Tiotropium (Spiriva) which is another type of long acting inhaler medication to help with widening the airways.
In this study, we wish to find out if two different types of beta blocker cause different effects on the airways in COPD patients. One type of beta blocker is more 'selective' in acting mainly on the heart, with the other type having more general or 'non-selective' effects on both the heart and lungs. By doing this we will also be able to look at how the beta blockers work alongside the 'usual' inhaler treatment described above.
Detailed description
Screening Visit A member of the research team will discuss the Patient Information Sheet with the participant, answer any questions posed and written informed consent will be obtained.
Prior to screen participants will be asked to withhold tiotropium for 48 hours ipratropium bromide for 12 hours and salbutamol for 6 hours.
A general physical examination will be carried out by a qualified medical practitioner.
A pregnancy test from a urine sample will be performed for all female participants with advice issued to both male and female participants to use contraception throughout the duration of the study.
The following will be measured:
Spirometry with sequential reversibility to 400μg salbutamol then 80 μg ipratropium bromide according to American Thoracic Society guidelines Resting Electrocardiogram Whole body plethysmography (where possible) Impulse Oscillometry
Oxygen saturations breathing room air after 5 mins rest Heart rate and blood pressure. 6 Minute Walk Test (if physically able)
Inhaler technique will be assessed and confirmed adequate.
Full blood count, renal function, electrolytes, liver enzymes and random blood glucose will be measured.
Participants will be checked against all inclusion and exclusion criteria. Those found to be eligible will proceed to the run-in period.
Run-in period Participants who are taking inhaled corticosteroids, combination inhalers, Long acting bata agonists or long-acting anti-muscarinics will have these discontinued.
All participants entering the run-in period will be commenced on Fostair (Beclometasone/Formoterol) 100/6, 2 puffs twice daily via spacer device for approximately 2 weeks.
Participants will be given a PiKO monitor to record domiciliary Forced expiratory volume1 and Forced expiratory Volume6 twice daily (approximately 12 hours apart) in a diary supplied by the department as well as domiciliary oxygen saturation and Heart Rate monitor to be recorded twice daily. They will also complete a daily diary of reliever use and symptoms. These will all be performed from the beginning of the run-in period to the end of the study.
At the end of run-in, participants will be again checked against all inclusion and exclusion criteria and the hief Investigator or medical investigator for the study will sign the declaration on the Case Report Form, to confirm the subject's suitability to receive the study drug according to study protocol. Those eligible will proceed to study visit 1. Those who do not fulfil the study criteria will be returned to their pre-study medication and their GP informed of any medically relevant data.
Study Visit 1 (Baseline 1) Participants will attend the department on the morning of their study visit.
Participants will be asked to withhold their ipratropium for 12 hours and salbutamol for 6 hours prior to visit.
Diaries of symptoms, reliever use and domiciliary FEV1 will be reviewed.
Baseline measurements to be recorded are:
IOS Slow Vital Capacity Spirometry Resting ECG Resting O2 sats HR and BP St George's Respiratory Questionnaire 6MWT (where physically possible and only if performed at screen) Echocardiogram (where technically possible) Serum (after at least 30mins supine posture): Aldosterone, Angiotensin II, BDNF, BNP, Potassium
Provided average HR>60bpm and average systolic BP>110mmHg the participant will be randomised to 1 of 2 beta-blocker treatments comprising:
- Carvedilol: 1 week of 3.125mg bid, 1 week of 6.25mg bid, 4 weeks of 12.5mg bid or
- Bisoprolol: 1 week of 1.25mg od, 1 week of 2.5mg od, 4 weeks of 5mg od
Participants will be given their first 4 weeks of randomised IMP for the treatment period at this study visit.
When titrating their beta-blocker at home, should the participant start to experience side-effects related to beta-blocker therapy or they find that their HR is dropping below 55bpm they will be informed to phone the department working hours) or the emergency mobile number (out of hours).
Participants will be allowed to complete each treatment arm on their maximum tolerated dose of beta-blocker, should this be less than the maximum prescribed dose.
Participants in both treatment arms will continue taking Fostair 100/6, 2 puffs bid via spacer device for the first 5 weeks of each treatment period. For the final (6th) week of each treatment period they will receive inhaled beclometasone dipropionate (as Clenil) 200μg, 2 puffs bid via spacer device, instead of Fostair.
Participants in both treatment arms will be given Tiotropium 18μg (via handihaler) od for the first 4 weeks of each treatment period. Tiotropium will then be discontinued for the final 2 weeks of each treatment period.
Participants will be given a salbutamol inhaler to use as initial reliever therapy along with an ipratropium inhaler second line on a PRN basis.
The IMPs will be issued to the participant by a member of the research team delegated the task. The allocation will be checked and countersigned by a second delegated member of staff.
Inhaler technique for the different devices will be checked.
A participant instruction and appointment leaflet will be issued and discussed fully with the participant and any questions answered. It will detail:
Emergency contact numbers Instructions on how to take heart rate and O2 sats measurements How to perform domiciliary FEV1 and FEV6 How to write in the diary Potential side effects of study drugs Recording of AEs and concomitant medication use Withholding times for relievers Titration/Discontinuation times for IMPs
Reminders to return medication and bottles at each visit
Study visit 2
Measurements to be recorded at this visit are:
IOS Slow VC Spirometry Resting O2 sats HR and BP (as previously described in 3.5.5) Resting ECG 6MWT (where physically possible and only if performed previously in study) SGRQ
Participants will be given their final 2 weeks of randomised IMP (at their maximum tolerated dose) for that treatment period.
Participants will discontinue their tiotropium for the remaining 2 weeks of the treatment period at this study visit.
Study visit 3
. As for study visit 2 with the addition of Serum BDNF, Potassium
Participants will discontinue their Fostair inhaler at this study visit and be given Clenil (beclometasone) 200ug, 2 puffs bid to take instead for the final week of the treatment period.
Study visit 4 As before plus, Echocardiogram (where technically possible) Serum (after at least 30mins supine posture): Aldosterone, Angiotensin II, BDNF, BNP, Potassium
Participants will finish treatment period 1 at this point and enter a 2 week period of washout (of beta-blocker) prior to crossing over to the other treatment arm.
Participants will discontinue their Clenil and beta-blocker and return to taking Fostair 100/6, 2 puffs bid for the 2 week washout period.
Study Visit 5 (Baseline 2)
Measurements to be recorded are:
IOS Slow VC Spirometry Resting ECG Resting O2 sats HR and BP (as previously described in 3.5.5) SGRQ 6MWT (where physically possible and only if performed at screen) Serum (after at least 30mins supine posture): Aldosterone, Angiotensin II, BDNF, BNP, Potassium
Provided average HR>60bpm and average systolic BP>110mmHg the participant will be crossed over to the beta-blocker treatment that they have not yet received (based on original randomisation) comprising:
- Carvedilol: 1 week of 3.125mg bid, 1 week of 6.25mg bid, 4 weeks of 12.5mg bid
- Bisoprolol: 1 week of 1.25mg od, 1 week of 2.5mg od, 4 weeks of 5mg od Measurements will be repeated as per Study Visit 1.
Study Visits 6 \& 7 Visit 6 will be the same as visit 2 Visit 7 will be the same as visit 3 Study Visit 8
Measurements to be recorded are:
IOS Slow VC Spirometry Resting ECG Resting O2 sats HR and BP (as previously described in 3.5.5) SGRQ 6MWT (where physically possible and only if performed at screen) Echocardiogram (where technically possible) Serum (after at least 30mins supine posture): Aldosterone, Angiotensin II, BDNF, BNP, Potassium
Participants will finish treatment period 2, and, therefore, the study at this point. They will be returned to their usual prescribed medication.
End of Study Period. The study will be complete when the last enrolled participant completes the last visit
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Carvedilol | Experimental | Drug: Carvedilol, Drug: Beclometasone/formoterol, Drug: Tiotropium, Drug: BeclometasoneBeclometasone/Formoterol Beclometasone Tiotropium |
| Bisoprolol | Active comparator | Drug: Bisoprolol, Drug: Beclometasone/formoterol, Drug: Tiotropium, Drug: BeclometasoneBeclometasone/Formoterol Beclometasone Tiotropium |
Who may qualify
- Ages
- 40 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Moderate to severe COPD (GOLD stage 2 and 3)
- FEV1 30-80% predicted
- No exacerbation in previous 3 months
- Smoking history ≥ 10 pack years
- Oxygen saturations≥ 92% on room air at rest
Key exclusion criteria (13 listed)
- Use of domiciliary oxygen
- History of other primary obstructive lung disease including asthma or bronchiectasis
- History of unstable angina, uncontrolled hypertension or heart failure NYHA class 3-4
- Overt clinical signs of right heart failure
- Average resting systolic BP<110mmHg
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 |
|---|---|---|
| CarvedilolDose titration: 3.125mg bid for 1 week, 6.25mg bid for 1 week, 12.5mg bid for 4 weeks. | Drug | Carvedilol |
| BisoprololDose titration: 1.25mg od for 1 week, 2.5mg od for 1 week, 5mg for 4 weeks. | Drug | Bisoprolol |
| Beclometasone/formoterolAlso: Fostair 100/62 puffs bid for first 5 weeks in each treatment arm | Drug | Bisoprolol, Carvedilol |
| TiotropiumAlso: Spiriva 18mcg1 puff daily for first 4 weeks of each treatment arm | Drug | Bisoprolol, Carvedilol |
| BeclometasoneAlso: Clenil 2002 puffs bid for final week (week 6) of each treatment arm | Drug | Bisoprolol, Carvedilol |
Primary outcome
Change in airway resistance at 5HZ (R5) using impulse oscillometry from baseline.
Time frame: 4, 5 and 6 weeks of each treatment period
6 secondary outcomes
Change in remaining impulse oscillometry measurements from baseline
Time frame: 4, 5 and 6 weeks of each treatment period
Change in spirometry measurements from baseline
Time frame: 4, 5 and 6 weeks of each treatment period
Change in echocardiogram parameters from baseline
Time frame: At 6 weeks of each treatment period
Change in vital signs from baseline
Time frame: 4, 5, and 6 weeks in each treatment period
Change in six minute walk test distance from baseline
Time frame: 4, 5 and 6 weeks of each treatment periods.
Change in St George's Respiratory Questionnaire score from baseline
Time frame: 4, 5 and 6 weeks in each treatment arm
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Apr 2019.
- Results publication: PubMed 29025008Jabbal S, Anderson W, Short P, Morrison A, Manoharan A, Lipworth BJ. Cardiopulmonary interactions with beta-blockers and inhaled therapy in COPD. QJM. 2017 Dec 1;110(12):785-792. doi: 10.1093/qjmed/hcx155.
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Pulmonary Disease, Chronic Obstructive (COPD), Hypercapnia
RecruitingPhase 2
Phase 2b Efficacy and Safety Study of AERO-007, an Inhaled LABA+LAMA Combination for Nebulization Delivery in COPD Patients
COPD, Chronic Obstructive Pulmonary Disease (COPD)
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.
William J Anderson, MBChB principal investigator
University of Dundee
Brian J Lipworth, MD study director
University of Dundee
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 Carvedilol, Bisoprolol and Beclometasone/formoterol in people with Chronic Obstructive Pulmonary Disease, run by University of Dundee at 1 site in United Kingdom.
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 6 inclusion and 13 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: finished, as of the sponsor's last update on 23 Apr 2019. 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 United Kingdom. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in airway resistance at 5HZ (R5) using impulse oscillometry from baseline. (time frame: 4, 5 and 6 weeks of each treatment period). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01656005, which also lists 1 linked publication.
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 23 Apr 2019.