Coronary Artery DiseaseNCT02791087
Investigation of the Role of Hemodynamics in Re-stenosis of CABG Patients
An observational study of Coronary Artery Disease and Stable Angina, run by National Heart Centre Singapore at 1 site in Singapore.
Trial summary
CFD simulations in this study provide detailed hemodynamics information, which cannot be obtained from cardiac images alone. The investigators hypothesize that our proposed simulations will provide strong correlation between hemodynamic parameters, such as WSSG and SPA, and clinically identified graft stenosis. Read more about this study
- Who is it for?
- Ages 21 to 80 years
- Conditions the study is for
- Coronary Artery Disease, Stable Angina, Unstable Angina
- What is being tested?
- Computed Tomography Angiography and Intra-operative graft flow rate measurement
- How many people
- 54 participants
- Where
- 1 siteSingapore
- Study dates
- Jun 2013to Oct 2018
- Phase
- Observational
- 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 21 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Potential patients scheduled for Coronary Bypass Surgery identified at NHCS cardiology inpatient and patients with stable/unstable angina from cardiology inpatient and outpatient clinic.
Who may be able to join
- Aged 21-80.
- Undergoing or underwent CABG with at least one saphenous vein graft. (Only for recruitment of CABG patients)
- No known history of coronary artery disease (only for recruitment of volunteers with Stable/unstable angina).
Who cannot join
- Individuals unable to provide informed consent.
- Non-cardiac illness with life expectancy <2 years.
- Pregnant state.
- Allergy to iodinated contrast.
- Significant arrhythmia; heart rate ≥ 100 beats/min; systolic blood pressure ≤90 mmHg.
- Renal dysfunction(Glomerular filtration rate (GFR) <30 mL/min/1.73m2).
- Contraindication to beta blockers or nitroglycerin.
- Canadian Cardiovascular Society class IV angina.
Trial locations and contacts
1 site in 1 country.
About this study
CFD simulations in this study provide detailed hemodynamics information, which cannot be obtained from cardiac images alone. The investigators hypothesize that our proposed simulations will provide strong correlation between hemodynamic parameters, such as WSSG and SPA, and clinically identified graft stenosis. These correlations will allow the investigators to identify the future patients at high risk of graft stenosis and lead to future researches on optimizing and refining surgical plans, such as finding optimal proximal and distal anastomoses locations, optimal graft length and diameter, which could lead to improved longevity of the graft. Once CFD coupled shape optimizer is validated, it could be part of the surgical simulator to help in training the next generation physicians. It could provide new viewpoints for assessing whether some modified surgical techniques are better or not. It could also aid in designing and evaluating the vascular medical devices, including stent, artificial graft, and etc., which would lead to better surgical outcome.
Read the detailed description
Since the introduction of saphenous vein grafting in the late 1960s, CABG, with or without arterial conduits, remains the gold standard for management of intractable angina due to coronary artery occlusive disease. According to the statistics of American Heart Association, 571,000 of bypass procedures were performed on 355,000 patients in 1999. In Singapore, 831 CABG surgeries were carried out in 2011. With the aging of society, the number of bypass operations is suspected to keep increasing over the years.
However, the CABG was not without complications. The saphenous vein, which is the most commonly used vessel for grafting, provides only palliation of the ongoing process. Approximately 15% to 20% saphenous vein grafts occlude in the first year. An additional 2% to 5% grafts occlude each year between 2 to 10 years postoperatively. At 10 to 14 years, 50% of the grafts are occluded. Similar data is reported in 2011 ACCF/AHA CABG guideline. Although thrombosis, intimal hyperplasia and atherosclerosis are found by pathological examinations, the exact mechanism of stenosis is still not fully understood. The investigators hypothesize that localized hemodynamic parameters is related to the sites of graft occlusion.
Hemodynamic parameters are propounded to be involved in localization of arterial stenosis in literatures. High wall shear stress was found to lead abnormal endothelia cells by Fry on the study of thoracic aorta in dogs. Intimal thicken and atherosclerosis was found to be developed in the low WSS region when studying stenosis on postmortem human carotid bifurcations, synthetic grafts on dog's carotid arteries and human coronary arteries. Both high and low WSS segments was found to interplay with plaque development on human coronary arteries. Bovine aortic endothelial cells density was found to increase in the high wall shear stress gradient regions by Depaola and colleagues. Significantly increased WSSG was found at the throat of the cervical carotid stenosis by Schirmer and colleagues for 8 patients. Stress phase angle was proposed to be a useful indicator in predicting sites prone to atherosclerosis by Torii et al. when investigating a patient's right coronary artery with stenosis. Low-density lipoprotein transportation was proposed to be a useful indicator in predicting sites prone to atherosclerosis on human left coronary artery by Olgac and colleagues.
All of these hemodynamic parameters are related to the forces acting on the endocellar cells, especially the wall shear stress. Signaling pathways have been proposed, which mediate the mechano- chemical transduction in endothelial cells in response to disturbed WSS. Among the WSS-related parameters, WSSG and SPA may be the most important, as WSSG measures the impact of changes in surface forces, while SPA refers to the phase angle between WSS and WCS. Therefore direct study on the human with CABG is necessary to provide strong correlation between graft stenosis and hemodynamic parameters, which would be helpful in identifying the patients at high risk of re-stenosis and optimizing the surgery from a mechanical standpoint. The current project aims to fill in this gap.
- Conditions
- Coronary Artery Disease, Stable Angina, Unstable Angina
- Being tested
- Computed Tomography Angiography, Intra-operative graft flow rate measurement
- Medical subject headings
- Coronary Artery Disease, Angina, Stable, Angina, Unstable
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Computed Tomography AngiographyOther
The CTA is non-invasive and is used commonly for patients who have chest pain to assess the coronary artery disease, prior to the more invasive coronary angiogram.
Intra-operative graft flow rate measurementOther
This procedure involves the insertion of a Medistim Ultrasound Transit Time Flow Probe into the graft vessel to measure its flow rate. This technique is commonly used for evaluating graft opening during CABG surgery.
| Study group | Role | What they receive |
|---|---|---|
| Coronary Artery Disease for CABG | Patients undergoing or underwent Coronary Bypass Surgery with at least one saphenous vein graft. Intra-operative graft flow rate measurement will be done during CABG surgery. Receives: Other: Computed Tomography Angiography; Other: Intra-operative graft flow rate measurement | |
| Stable/Unstable Angina | Patients with no known history of coronary artery disease undergoing Computed Tomography Angiography scan due to stable/Unstable Angina. Receives: Other: Computed Tomography Angiography |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evidence of allergic reaction due to CTA scan contrast
Measured: Within first day after scan
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jun 2016 (estimated)
- Study startJun 2013
- Primary completionOct 2018
- Study completionOct 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Coronary Artery 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
- Observational
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 54 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Heart Centre Singapore
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Junmei Zhang, Principal investigator, National Heart Centre Singapore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02791087
- Sponsor's protocol ID
- 2013/366/C
- Status last verified
- Sep 2017
- First submitted
- 31 May 2016
- Last updated
- 7 Jun 2019
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigation of the Role of Hemodynamics in Re-stenosis of CABG Patients
- ClinicalTrials.gov ID
- NCT02791087
- Acronym / sponsor ID
- 2013/366/C
- Conditions
- Coronary Artery Disease, Stable Angina, Unstable Angina
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 54 participants (actual)
- Lead sponsor
- National Heart Centre SingaporeUniversity, hospital or other
- Study start
- Jun 2013
- Primary completion
- Oct 2018 (actual)
- Study completion
- Oct 2018 (actual)
- First posted
- 6 Jun 2016 (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.
CFD simulations in this study provide detailed hemodynamics information, which cannot be obtained from cardiac images alone. The investigators hypothesize that our proposed simulations will provide strong correlation between hemodynamic parameters, such as WSSG and SPA, and clinically identified graft stenosis. These correlations will allow the investigators to identify the future patients at high risk of graft stenosis and lead to future researches on optimizing and refining surgical plans, such as finding optimal proximal and distal anastomoses locations, optimal graft length and diameter, which could lead to improved longevity of the graft. Once CFD coupled shape optimizer is validated, it could be part of the surgical simulator to help in training the next generation physicians. It could provide new viewpoints for assessing whether some modified surgical techniques are better or not. It could also aid in designing and evaluating the vascular medical devices, including stent, artificial graft, and etc., which would lead to better surgical outcome.
Detailed description
Since the introduction of saphenous vein grafting in the late 1960s, CABG, with or without arterial conduits, remains the gold standard for management of intractable angina due to coronary artery occlusive disease. According to the statistics of American Heart Association, 571,000 of bypass procedures were performed on 355,000 patients in 1999. In Singapore, 831 CABG surgeries were carried out in 2011. With the aging of society, the number of bypass operations is suspected to keep increasing over the years.
However, the CABG was not without complications. The saphenous vein, which is the most commonly used vessel for grafting, provides only palliation of the ongoing process. Approximately 15% to 20% saphenous vein grafts occlude in the first year. An additional 2% to 5% grafts occlude each year between 2 to 10 years postoperatively. At 10 to 14 years, 50% of the grafts are occluded. Similar data is reported in 2011 ACCF/AHA CABG guideline. Although thrombosis, intimal hyperplasia and atherosclerosis are found by pathological examinations, the exact mechanism of stenosis is still not fully understood. The investigators hypothesize that localized hemodynamic parameters is related to the sites of graft occlusion.
Hemodynamic parameters are propounded to be involved in localization of arterial stenosis in literatures. High wall shear stress was found to lead abnormal endothelia cells by Fry on the study of thoracic aorta in dogs. Intimal thicken and atherosclerosis was found to be developed in the low WSS region when studying stenosis on postmortem human carotid bifurcations, synthetic grafts on dog's carotid arteries and human coronary arteries. Both high and low WSS segments was found to interplay with plaque development on human coronary arteries. Bovine aortic endothelial cells density was found to increase in the high wall shear stress gradient regions by Depaola and colleagues. Significantly increased WSSG was found at the throat of the cervical carotid stenosis by Schirmer and colleagues for 8 patients. Stress phase angle was proposed to be a useful indicator in predicting sites prone to atherosclerosis by Torii et al. when investigating a patient's right coronary artery with stenosis. Low-density lipoprotein transportation was proposed to be a useful indicator in predicting sites prone to atherosclerosis on human left coronary artery by Olgac and colleagues.
All of these hemodynamic parameters are related to the forces acting on the endocellar cells, especially the wall shear stress. Signaling pathways have been proposed, which mediate the mechano- chemical transduction in endothelial cells in response to disturbed WSS. Among the WSS-related parameters, WSSG and SPA may be the most important, as WSSG measures the impact of changes in surface forces, while SPA refers to the phase angle between WSS and WCS. Therefore direct study on the human with CABG is necessary to provide strong correlation between graft stenosis and hemodynamic parameters, which would be helpful in identifying the patients at high risk of re-stenosis and optimizing the surgery from a mechanical standpoint. The current project aims to fill in this gap.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Coronary Artery Disease for CABG | – | Other: Computed Tomography Angiography, Other: Intra-operative graft flow rate measurementPatients undergoing or underwent Coronary Bypass Surgery with at least one saphenous vein graft. Intra-operative graft flow rate measurement will be done during CABG surgery. |
| Stable/Unstable Angina | – | Other: Computed Tomography AngiographyPatients with no known history of coronary artery disease undergoing Computed Tomography Angiography scan due to stable/Unstable Angina. |
Who may qualify
- Ages
- 21 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Potential patients scheduled for Coronary Bypass Surgery identified at NHCS cardiology inpatient and patients with stable/unstable angina from cardiology inpatient and outpatient clinic.
Key inclusion criteria (3 listed)
- Aged 21-80.
- Undergoing or underwent CABG with at least one saphenous vein graft. (Only for recruitment of CABG patients)
- No known history of coronary artery disease (only for recruitment of volunteers with Stable/unstable angina).
Key exclusion criteria (8 listed)
- Individuals unable to provide informed consent.
- Non-cardiac illness with life expectancy <2 years.
- Pregnant state.
- Allergy to iodinated contrast.
- Significant arrhythmia; heart rate ≥ 100 beats/min; systolic blood pressure ≤90 mmHg.
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 |
|---|---|---|
| Computed Tomography AngiographyThe CTA is non-invasive and is used commonly for patients who have chest pain to assess the coronary artery disease, prior to the more invasive coronary angiogram. | Other | Coronary Artery Disease for CABG, Stable/Unstable Angina |
| Intra-operative graft flow rate measurementThis procedure involves the insertion of a Medistim Ultrasound Transit Time Flow Probe into the graft vessel to measure its flow rate. This technique is commonly used for evaluating graft opening during CABG surgery. | Other | Coronary Artery Disease for CABG |
Primary outcome
Evidence of allergic reaction due to CTA scan contrast
Time frame: Within first day after scan
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 7 Jun 2019.
- Individual participant dataSharing planned: No
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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.
Junmei Zhang principal investigator
National Heart Centre Singapore
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Coronary Artery Disease and Stable Angina, run by National Heart Centre Singapore at 1 site in Singapore.
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 3 inclusion and 8 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 7 Jun 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 Singapore. 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.
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?
Evidence of allergic reaction due to CTA scan contrast (time frame: Within first day after scan). 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 7 Jun 2019.