Improving cardiac function in high-risk surgical patients: exercise testing, biomarkers and beta-blockade

ISRCTN ISRCTN95679074
DOI https://doi.org/10.1186/ISRCTN95679074
EudraCT/CTIS number 2017-002443-15
Secondary identifying numbers 3.0 (08/08/2017)
Submission date
22/01/2018
Registration date
23/01/2018
Last edited
04/01/2021
Recruitment status
Stopped
Overall study status
Stopped
Condition category
Surgery
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year

Plain English summary of protocol

Background and study aims
Major elective abdominal surgery carries a significant risk of mortality (death) and morbidity (illness), a proportion of which is directly due to specific cardiac disease, particularly heart failure. Before people have major surgery they undergo a simple test on a cycle machine, which helps to determine if there are likely to be any particular problems during or after the surgery. These results are used to plan the best way to look after patients around the time of their operation as part of their standard care. For a small number of patients the cycle exercise test shows that the heart function is not as good as expected, with these patients showing a higher risk of developing serious problems after surgery. The aim of this study is to see whether the heart function of surgical patients can be improved using a medication to improve heart function (bisoprolol), thus reducing the risk of mortality and morbidity for these patients.

Who can participate?
Patients aged 55 years or over who are scheduled for major abdominal surgery

What does the study involve?
Participants are prescribed bisoprolol to be taken daily. After 10 days at a follow up appointment their heart function is assessed.

What are the possible benefits and risks of participating?
Taking bisoprolol may improve the performance of the heart and by reduce the risks of having the operation. No additional risks are expected as bisoprolol is fully licensed for use in improving heart performance. There are additional assessments required for the study, which may extend a clinic visit.

Where is the study run from?
York Teaching Hospital NHS Foundation Trust (UK)

When is the study starting and how long is it expected to run for?
March 2016 to February 2021

Who is funding the study?
Elsie May Sykes Charitable Research Fund (UK)

Who is the main contact?
Mia Porteous, Mia.Porteous@york.nhs.uk

Contact information

Ms Mia Porteous
Public

Room 147, 3rd Floor
Junction 8
York Hospital
Wigginton Road
York
YO31 8HE
United Kingdom

Phone +44 (0)1904 725129
Email Mia.Porteous@york.nhs.uk

Study information

Study designProspective proof of concept case series
Primary study designInterventional
Secondary study designNon randomised study
Study setting(s)Hospital
Study typeTreatment
Participant information sheet Not available in web format, please use the contact details to request a patient information sheet
Scientific titleImproving cardiac function in high-risk surgical patients: exercise testing, biomarkers and beta-blockade
Study acronymICAF-BETA
Study objectivesAdministration of Bisoprolol to participants with impaired VE/VCO2 will improve cardiac function.
Ethics approval(s)Yorkshire & The Humber - Leeds West Research Ethics Committee, 25/08/2017, ref: 17/YH/0222
Health condition(s) or problem(s) studiedPatients with impaired VE/VCO2 scheduled for major intra-abdominal surgery
InterventionPatients aged 55 years or over, scheduled for major abdominal surgery will be eligible. These patients will be sent information about the study prior to their routine pre-assessment appointment. Those patients who consent will undergo screening as part of their appointment; if they meet all inclusion criteria they will be enrolled and prescribed Bisoprolol 2.5mg to be taken daily for a minimum of 7 days prior to surgery. After 10 days a follow up appointment will be required to review heart function.
Intervention typeDrug
Pharmaceutical study type(s)
PhaseNot Applicable
Drug / device / biological / vaccine name(s)Bisoprolol
Primary outcome measureVentilator equivalent for CO2 (VE/VCO2), measured at anaerobic threshold or nadir using CO2 output prior to surgery
Secondary outcome measures1. Beta-natriuretic peptide, measured using blood test at baseline and 10 days post IMP commencement
2. Systolic and diastolic function, measured using ECG at baseline and 10 days post IMP commencement
3. Anaerobic threshold, measured using CPET at baseline and 10 days post IMP commencement
4. Myocardial abnormality (VO2/HR response, VO2/Watt response), measured using CPET at baseline and 10 days post IMP commencement
Overall study start date28/03/2016
Completion date01/02/2021
Reason abandoned (if study stopped)Participant recruitment issue

Eligibility

Participant type(s)Patient
Age groupAdult
SexBoth
Target number of participants44
Key inclusion criteria1. Aged 55 years or over
2. Scheduled for major intra-abdominal surgery
3. Presenting for routine CPET as part of pre-assessment
4. Not currently taking any BB medication and not taken BB medication within 1 month prior
5. Consent to GP being informed
6. VE/VCO2 34 or greater on CPET, as either the value measured at VO2@AT, or the lowest measured value, plus at least one of the following:
6.1. Presence of a known history of a clinical risk factor for major adverse cardiac events (MACE) after surgery
6.1.1. Ischaemic heart disease
6.1.2. Cerebrovascular disease
6.1.3. Renal insufficiency (creatinine > 170 mol.L-1)
6.1.4. Chronic heart failure
6.2. Evidence of abnormal myocardial response on exercise testing
6.2.1. Flattened or inflecting oxygen uptake to heart rate response (oxygen pulse response, VO2/HR, panel 2)
6.2.2. Flattened or inflecting oxygen uptake to work rate response (VO2/Watt, panel 3)
6.3. Anaerobic threshold <11ml/kg/min
Key exclusion criteria1. Refusal or unable to give informed consent
2. Fewer than 7 days before scheduled surgery at pre-assessment appointment surgery
3. Current beta blocker medication or having taken any beta blocker within 1 month prior
4. Contra-indications to BB medication including:
4.1. Bronchial asthma
4.2. Reversible airways disease
4.3. Decompensated heart failure (NYHA class IV)
4.4. Fluid overloaded
4.5. Hypotensive
4.6. Severe liver impairment
4.7. Second or third degree A-V block (unless pacemaker fitted)
4.8. SA block
4.9. Sick sinus syndrome (unless pacemaker inserted)
4.10. Cardiogenic shock
4.11. Bradycardia (heart rate less than 60 bpm)
4.12. Prinzmetal's angina
4.13. Untreated Phaeochromocytoma
4.14. Metabolic acidosis
4.15. Poor blood circulation in the hands and feet
4.16. Severe peripheral arterial insufficiency
4.17. Known hypersensitivity to bisoprolol or its ingredients (lactose monohydrate, silica colloidal anhydrous, crospovidone (Type A), crospovidone (Type B), povidone 30, sucrose, magnesium stearate)
4.18. Co-prescription with negative chronotropic agents such as digoxin, diltiazem, verapamil, amiodarone
4.19. Co-prescription with medications that affect the plasma concentrations of bisoprolol such as rifampin, cimetidine, quinidine, fluoxetine, paroxetine, propafenone, digoxin, reserpine, monoamine oxidase inhibitors, clonidine
Date of first enrolment01/02/2018
Date of final enrolment01/01/2020

Locations

Countries of recruitment

  • England
  • United Kingdom

Study participating centre

York Teaching Hospital NHS Foundation Trust
Wigginton Road
York
YO30 4SR
United Kingdom

Sponsor information

York Teaching Hospital NHS Foundation Trust
Hospital/treatment centre

Wigginton Road
York
YO31 8HE
England
United Kingdom

Phone +44 (0)1904 725123
Email deborah.phillips@york.nhs.uk
ROR logo "ROR" https://ror.org/027e4g787

Funders

Funder type

Charity

Elsie May Sykes Charitable Research Fund

No information available

Results and Publications

Intention to publish date31/12/2020
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryData sharing statement to be made available at a later date
Publication and dissemination planDetails are not yet finalised but results will be published in appropriate journals.
IPD sharing planThe data sharing plans for the current study are unknown and will be made available at a later date.

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
HRA research summary 28/06/2023 No No

Editorial Notes

04/01/2021: The following changes have been made:
1. The overall trial status and recruitment have been changed to 'Stopped' since the study was prematurely terminated.
2. The public contact has been changed.
22/05/2019: Internal review.