Abdominal Aortic Aneurysm Patients Under SurveillanceEarly Phase 1NCT02106286
Effects of Beta-blockade on Cardiopulmonary Exercise Testing
A Early Phase 1 study testing Bisoprolol in people with Abdominal Aortic Aneurysm Patients Under Surveillance, run by Michelle Mossa at 1 site in United Kingdom.
Trial summary
A major determinant of perioperative mortality is the inability of the heart to increase its output in response to surgical stress. This is termed perioperative cardiac failure (PCF), and may only be apparent postoperatively when oxygen demand is increased. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Abdominal Aortic Aneurysm Patients Under Surveillance
- What is being tested?
- Bisoprolol
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 55 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Feb 2011to Dec 2013
- Phase
- Early Phase 1
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- >18 years of age inclusive, undergoing major surgery who are already on therapy with beta blockers
- >18 years of age, undergoing major surgery who are not on beta blockers
- Patient able to consent to study protocol
- Ability to perform CPET on an exercise bike
- AAA patients under surveillance.
Who cannot join
- Known contraindication to bisoprolol (known intolerance, asthma or history of bronchospasm, II or III degree heart block, treatment with verapamil or ivrabadine, sinus bradycardia, Prinzmetal's angina),
- Severe ischaemic heart disease (including acute coronary syndrome within 3 months of recruitment),
- Inability to use an exercise bike
- Stage IV and V chronic kidney disease
- Uncontrolled hypertension
- Patients withholding informed consent
Show all 9Show fewer
- Patients unable to give informed consent due to mental incapacity
- Patients who find uncomfortable and anxiety provoking performing an exercise test
- Patients who present contraindications (relative/absolute) to their first initial CPET based on the American Thoracic Society (ATS) exercise testing guidelines.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Influence of Beta-blockade on Cardiopulmonary Function Measured by Cardiopulmonary Exercise Testing
A major determinant of perioperative mortality is the inability of the heart to increase its output in response to surgical stress. This is termed perioperative cardiac failure (PCF), and may only be apparent postoperatively when oxygen demand is increased. The risk of perioperative cardiac complications is the summation of the individual patient's risk and cardiac stress related to the surgical procedure1. The functional capacity of the patient determines their ability to support the postoperative demand of increased oxygen consumption, and therefore of cardiac output. Exercise capacity is one of the most powerful predictors of cardiovascular and all cause mortality2. Cardiopulmonary exercise test (CPET) is an established investigation used, among other applications, in the preoperative assessment of patient fitness for surgery3. CPET involves monitoring the electrocardiographic trace and the exhaled gas mixture (particularly CO2, whose production depends on aerobic metabolism), during incremental exercise (usually on an exercise bike), on room air. Several parameters can be measured during CPET, including maximal systemic oxygen delivery, the anaerobic threshold (the oxygen delivery value at which anaerobic metabolism begins), maximum workload, and ST segment depression/elevation (as in a standard exercise tolerance test). The cardiopulmonary "performance" during CPET has been correlated with postoperative outcome3. Pulmonary function tests will be performed in order to assess lung function.
It is well known that therapy with beta-blockers in patients with ischaemic heart disease and cardiac failure reduces perioperative morbidity and mortality4-7. However, beta blockers reduce myocardial contractility and the heart rate response to adrenergic stimulation, thus blunting the physiological response to stress/surgery/exercise. Whilst this mechanism may protect the heart perioperatively, it may decrease the ability of some patients to withstand other complications. This potential decrease in "performance" has never been quantified.
Read more
There is no agreement on whether preoperative CPET should be performed on or off beta-blockers and, at Aintree in particular, it is standard procedure to take patients off beta-blockers prior to their CPET. Some argue that, as beta-blockade should be maintained in the perioperative period, CPET should be performed on medications, even if these could mask the presence significant ischaemic heart disease (a significant, modifiable, risk factor for surgery by beta blockade), and even if it is not always possible to maintain beta-blockade throughout the whole postoperative period. For these reasons, other clinicians prefer to perform CPET off beta-blockers, thus, potentially, overestimating the perioperative cardiorespiratory "performance", which may be diminished once the medications are resumed. Patients on long-term beta blockade may develop some tolerance to the medications, so the effect of acute and chronic beta blockade on cardiorespiratory performance may also be different.
Aim To compare cardiopulmonary performances on and off beta blockers as objectively assessed by cardiopulmonary exercise testing.
Read the detailed description
Study design
We propose an interventional study investigating the effects of acute and chronic beta-blockade on cardiorespiratory performance prior to elective surgery.
We aim to recruit 64 abdominal aortic aneurysm (AAA) patients under surveillance who will undergo 2 cardiopulmonary exercise tests to investigate the effect of beta blockade on cardiopulmonary performance. This sample size is calculated by using a 2-tailed sample t-test, with 90% power to detect an estimated increase of 10% in oxygen delivery (VO2) at anaerobic threshold. We also estimated a drop-out rate of about 25% which is built into our power calculation estimates.
Interventions
Patients on long term beta blockade will be studied to investigate the effect of chronic beta blocker use. They will undergo two CPETs, the first on beta blockers, the second after discontinuing their beta blocker for at least 48 hours.
Patients not on beta blockers will be studied to investigate the effect of acute beta blockade. They will undergo two CPETs, the first off medication, the second after commencement of beta blockade (weight adjusted, started 48 hours prior to CPET).
Potential subjects will be provided with the patient information sheet in clinic, 1-2 weeks prior to their initial CPET. They will be given at least 1 week to consider the study in which the investigators will follow them up via a telephone call. Informed consent to participate in the study will be obtained at their initial (standard care) CPET.
All consenting subjects will perform exercise using electro-magnetically braked equipment during a ramped-incremental protocol in two different occasions. Prior to the tests full lung function tests will be performed by body plethysmography. The exercise tests will be performed with subjects wearing nose clips and breathing through a mouthpiece throughout the test. The initial cycling workload will be zero but will progressively increase at a rate of 10-15 Watts/min. After a resting period of 30 seconds and 2 minutes warm up subjects will stop when they can cycle no further. All gas exchange parameters will be measured and a metabolic cart, heart rate and oxygen saturation will be monitored at pre and post testing.
Subjects will also be asked to score their perceived breathlessness and leg fatigue using modified Borg scores every minute during exercise, and inspiratory capacity will be measured every minute during the exercise test.
At the end of this test, they will be given a date for the 2nd CPET and a prescription for oral bisoprolol once daily (dose adjusted to patients body weight), to be started 48 hours prior to the test (two doses in total). Patients will be informed of potential side effects of the medications at this visit. This will be weight adjusted with a specific dose as follows: 1.25 mg if patent weighs 50-75 kg, 2.5 mg if 75-100 kg and 3.75 mg if >100 kg.
Patients will then attend for the 2nd CPET, following which bisoprolol will be discontinued or continued based on clinical indication.
If patients are already chronically on a beta blocker, they will have their first CPET while on medication, and then will be asked to stop the medication for a period of 48 hours before the second CPET. It is standard procedure to take the patient off beta blockers prior to their CPET at Aintree University Hospital. Patients will be informed of potential risks of stopping their beta blocker at their first visit. The beta blocker will be restarted or discontinued based on clinical indication after the second CPET.
- Being tested
- Bisoprolol
- Keywords
- Cardiopulmonary exercise test, surgery, abdominal aortic aneurysm, anaerobic threshold, fitness, beta-blockers
- Medical subject headings
- Aortic Aneurysm, Abdominal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BisoprololDrug
| Study group | Role | What they receive |
|---|---|---|
| Bisoprolol | Active comparator | Patients not betablocked at baseline receive an acute 72hr dose of beta blocker therapy before CPET Receives: Drug: Bisoprolol |
| No Bisoprolol | No intervention | No beta blocker given |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in oxygen uptake
Measured: Baseline and 72hours post beta-blockade
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Apr 2014 (estimated)
- Study startFeb 2011
- Primary completionDec 2013
- Study completionDec 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Abdominal Aortic Aneurysm Patients Under SurveillanceStudies 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
- Early Phase 1
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Investigator
- Enrolment
- 55 participants (actual)
Sponsor and investigators
- Lead sponsor
- Michelle Mossa
- Sponsor type
- Other government
- Responsible party
- Sponsor-investigator, Michelle Mossa, Liverpool University Hospitals NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02106286
- Sponsor's protocol ID
- 11/NW/0810
- Status last verified
- Apr 2014
- First submitted
- 31 Mar 2014
- Last updated
- 8 Apr 2014
- Results posted
- No
- Data monitoring committee
- No
Publications
Key A, Parry M, West MA, Asher R, Jack S, Duffy N, Torella F, Walker PP. Effect of beta-blockade on lung function, exercise performance and dynamic hyperinflation in people with arterial vascular disease with and without COPD. BMJ Open Respir Res. 2017 Apr 5;4(1):e000164. doi: 10.1136/bmjresp-2016-000164. eCollection 2017.
PubMed 28409004West MA, Parry M, Asher R, Key A, Walker P, Loughney L, Pintus S, Duffy N, Jack S, Torella F. The Effect of beta-blockade on objectively measured physical fitness in patients with abdominal aortic aneurysms--A blinded interventional study. Br J Anaesth. 2015 Jun;114(6):878-85. doi: 10.1093/bja/aev026. Epub 2015 Feb 24.
PubMed 25716221
Study at a glance
From the registry record, last updated by the sponsor on 8 Apr 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Influence of Beta-blockade on Cardiopulmonary Function Measured by Cardiopulmonary Exercise Testing
- ClinicalTrials.gov ID
- NCT02106286
- Acronym / sponsor ID
- 11/NW/0810
- Keywords
- Cardiopulmonary exercise test, surgery, abdominal aortic aneurysm, anaerobic threshold, fitness, beta-blockers
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 55 participants (actual)
- Lead sponsor
- Michelle MossaOther government
- Study start
- Feb 2011
- Primary completion
- Dec 2013 (actual)
- Study completion
- Dec 2013 (actual)
- First posted
- 8 Apr 2014 (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.
A major determinant of perioperative mortality is the inability of the heart to increase its output in response to surgical stress. This is termed perioperative cardiac failure (PCF), and may only be apparent postoperatively when oxygen demand is increased. The risk of perioperative cardiac complications is the summation of the individual patient's risk and cardiac stress related to the surgical procedure1. The functional capacity of the patient determines their ability to support the postoperative demand of increased oxygen consumption, and therefore of cardiac output. Exercise capacity is one of the most powerful predictors of cardiovascular and all cause mortality2. Cardiopulmonary exercise test (CPET) is an established investigation used, among other applications, in the preoperative assessment of patient fitness for surgery3. CPET involves monitoring the electrocardiographic trace and the exhaled gas mixture (particularly CO2, whose production depends on aerobic metabolism), during incremental exercise (usually on an exercise bike), on room air. Several parameters can be measured during CPET, including maximal systemic oxygen delivery, the anaerobic threshold (the oxygen delivery value at which anaerobic metabolism begins), maximum workload, and ST segment depression/elevation (as in a standard exercise tolerance test). The cardiopulmonary "performance" during CPET has been correlated with postoperative outcome3. Pulmonary function tests will be performed in order to assess lung function.
It is well known that therapy with beta-blockers in patients with ischaemic heart disease and cardiac failure reduces perioperative morbidity and mortality4-7. However, beta blockers reduce myocardial contractility and the heart rate response to adrenergic stimulation, thus blunting the physiological response to stress/surgery/exercise. Whilst this mechanism may protect the heart perioperatively, it may decrease the ability of some patients to withstand other complications. This potential decrease in "performance" has never been quantified.
There is no agreement on whether preoperative CPET should be performed on or off beta-blockers and, at Aintree in particular, it is standard procedure to take patients off beta-blockers prior to their CPET. Some argue that, as beta-blockade should be maintained in the perioperative period, CPET should be performed on medications, even if these could mask the presence significant ischaemic heart disease (a significant, modifiable, risk factor for surgery by beta blockade), and even if it is not always possible to maintain beta-blockade throughout the whole postoperative period. For these reasons, other clinicians prefer to perform CPET off beta-blockers, thus, potentially, overestimating the perioperative cardiorespiratory "performance", which may be diminished once the medications are resumed. Patients on long-term beta blockade may develop some tolerance to the medications, so the effect of acute and chronic beta blockade on cardiorespiratory performance may also be different.
Aim To compare cardiopulmonary performances on and off beta blockers as objectively assessed by cardiopulmonary exercise testing.
Detailed description
Study design
We propose an interventional study investigating the effects of acute and chronic beta-blockade on cardiorespiratory performance prior to elective surgery.
We aim to recruit 64 abdominal aortic aneurysm (AAA) patients under surveillance who will undergo 2 cardiopulmonary exercise tests to investigate the effect of beta blockade on cardiopulmonary performance. This sample size is calculated by using a 2-tailed sample t-test, with 90% power to detect an estimated increase of 10% in oxygen delivery (VO2) at anaerobic threshold. We also estimated a drop-out rate of about 25% which is built into our power calculation estimates.
Interventions
Patients on long term beta blockade will be studied to investigate the effect of chronic beta blocker use. They will undergo two CPETs, the first on beta blockers, the second after discontinuing their beta blocker for at least 48 hours.
Patients not on beta blockers will be studied to investigate the effect of acute beta blockade. They will undergo two CPETs, the first off medication, the second after commencement of beta blockade (weight adjusted, started 48 hours prior to CPET).
Potential subjects will be provided with the patient information sheet in clinic, 1-2 weeks prior to their initial CPET. They will be given at least 1 week to consider the study in which the investigators will follow them up via a telephone call. Informed consent to participate in the study will be obtained at their initial (standard care) CPET.
All consenting subjects will perform exercise using electro-magnetically braked equipment during a ramped-incremental protocol in two different occasions. Prior to the tests full lung function tests will be performed by body plethysmography. The exercise tests will be performed with subjects wearing nose clips and breathing through a mouthpiece throughout the test. The initial cycling workload will be zero but will progressively increase at a rate of 10-15 Watts/min. After a resting period of 30 seconds and 2 minutes warm up subjects will stop when they can cycle no further. All gas exchange parameters will be measured and a metabolic cart, heart rate and oxygen saturation will be monitored at pre and post testing.
Subjects will also be asked to score their perceived breathlessness and leg fatigue using modified Borg scores every minute during exercise, and inspiratory capacity will be measured every minute during the exercise test.
At the end of this test, they will be given a date for the 2nd CPET and a prescription for oral bisoprolol once daily (dose adjusted to patients body weight), to be started 48 hours prior to the test (two doses in total). Patients will be informed of potential side effects of the medications at this visit. This will be weight adjusted with a specific dose as follows: 1.25 mg if patent weighs 50-75 kg, 2.5 mg if 75-100 kg and 3.75 mg if >100 kg.
Patients will then attend for the 2nd CPET, following which bisoprolol will be discontinued or continued based on clinical indication.
If patients are already chronically on a beta blocker, they will have their first CPET while on medication, and then will be asked to stop the medication for a period of 48 hours before the second CPET. It is standard procedure to take the patient off beta blockers prior to their CPET at Aintree University Hospital. Patients will be informed of potential risks of stopping their beta blocker at their first visit. The beta blocker will be restarted or discontinued based on clinical indication after the second CPET.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- Single blind (investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Bisoprolol | Active comparator | Drug: BisoprololPatients not betablocked at baseline receive an acute 72hr dose of beta blocker therapy before CPET |
| No Bisoprolol | No intervention | –No beta blocker given |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- >18 years of age inclusive, undergoing major surgery who are already on therapy with beta blockers
- >18 years of age, undergoing major surgery who are not on beta blockers
- Patient able to consent to study protocol
- Ability to perform CPET on an exercise bike
- AAA patients under surveillance.
Key exclusion criteria (9 listed)
- Known contraindication to bisoprolol (known intolerance, asthma or history of bronchospasm, II or III degree heart block, treatment with verapamil or ivrabadine, sinus bradycardia, Prinzmetal's angina),
- Severe ischaemic heart disease (including acute coronary syndrome within 3 months of recruitment),
- Inability to use an exercise bike
- Stage IV and V chronic kidney disease
- Uncontrolled hypertension
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 |
|---|---|---|
| Bisoprolol | Drug | Bisoprolol |
Primary outcome
Change in oxygen uptake
Time frame: Baseline and 72hours post beta-blockade
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 8 Apr 2014.
- Derived from this study: PubMed 28409004Key A, Parry M, West MA, Asher R, Jack S, Duffy N, Torella F, Walker PP. Effect of beta-blockade on lung function, exercise performance and dynamic hyperinflation in people with arterial vascular disease with and without COPD. BMJ Open Respir Res. 2017 Apr 5;4(1):e000164. doi: 10.1136/bmjresp-2016-000164. eCollection 2017.
- Derived from this study: PubMed 25716221West MA, Parry M, Asher R, Key A, Walker P, Loughney L, Pintus S, Duffy N, Jack S, Torella F. The Effect of beta-blockade on objectively measured physical fitness in patients with abdominal aortic aneurysms--A blinded interventional study. Br J Anaesth. 2015 Jun;114(6):878-85. doi: 10.1093/bja/aev026. Epub 2015 Feb 24.
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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Bisoprolol in people with Abdominal Aortic Aneurysm Patients Under Surveillance, run by Michelle Mossa 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 5 inclusion and 9 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 8 Apr 2014. 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
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 oxygen uptake (time frame: Baseline and 72hours post beta-blockade). 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 NCT02106286, which also lists 2 linked publications.
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 8 Apr 2014.