Circulation, CollateralPhase 1/2IMAONCT02475408
Effect of Permanent Internal Mammary Artery Occlusion on Extracardiac Coronary Collateral Supply
A Phase 1/2 study testing Amplatzer vascular plug in people with Circulation, Collateral and Coronary Artery Disease, run by Insel Gruppe AG, University Hospital Bern at 1 site in Switzerland.
Trial summary
Coronary artery disease and the benefit of bypasses: Despite considerable advances in medicine, cardiovascular diseases remain the number one cause of death globally, primarily consequence of myocardial infarction (MI). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Circulation, Collateral, Coronary Artery Disease, Internal Mammary-Coronary Artery Anastomosis
- What is being tested?
- Amplatzer vascular plug
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteSwitzerland
- Study dates
- Dec 2014to Apr 2016
- Phase
- Phase 1/2
- 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
- Age > 18 years
- Referred for elective coronary angiography
- Written informed consent to participate in the study
- Significant stenosis of right coronary artery (FFR ≤0.80)
Who cannot join
- Acute coronary syndrome; unstable cardiopulmonary conditions, unstable angina pectoris
- Collateral flow index of right IMA <0.25
- Severe cardiac valve disease
- Congestive heart failure NYHA III-IV
- Prior coronary artery bypass surgery / prior cardiac surgery
- Coronary artery disease best treated by coronary artery bypass grafting
Show all 10Show fewer
- Coronary artery disease unsuitable for intracoronary pressure measurements
- Prior Q-wave myocardial infarction in the vascular territory undergoing collateral function determination
- Severe renal or hepatic failure
- Women of childbearing age
Trial locations and contacts
1 site in 1 country.
About this study
Coronary artery disease and the benefit of bypasses:
Despite considerable advances in medicine, cardiovascular diseases remain the number one cause of death globally, primarily consequence of myocardial infarction (MI). Coronary collaterals exert a protective effect by providing an alternative source of blood flow to a myocardial territory potentially affected by an acute coronary occlusion. Coronary collaterals represent pre-existing inter-arterial anastomoses and as such are the natural counter-part of surgically created bypasses. Sufficient coronary collaterals have been shown to confer a significant benefit in terms of overall mortality and cardiovascular events. In this regard, the concept of augmenting coronary collateral function as an alternative treatment strategy to alter the course of CAD, as well as to control symptoms, is attractive.
Read more
Durable promotion of coronary collateral circulation:
Before the advent of coronary artery bypass grafting, permanent augmentation of coronary collateral supply by a single structural modification has already been attempted. Bilateral ligation of the internal mammary arteries (IMA) was performed in CAD patients to alleviate angina pectoris and electrocardiographic (ECG) signs of ischemia. The prevalent in vivo function of natural IMA-to-coronary artery bypasses and their anti-ischemic effect has - for the first time - been recently demonstrated by our research group. The acute functional changes observed in response to temporary distal IMA balloon occlusion are expected to result in larger chronic structural adaptations of the IMA-to-coronary-artery connections when the distal IMA is permanently occluded. In contrast to the previously employed arteriogenic approaches in humans, the attractiveness of such an intervention lies in the potential durability of the effect.
In a first step, catheter-based IMA occlusion ought to be conceptually investigated in the setting of the less frequently grafted right IMA among patients with ischemia in the right coronary artery territory.
Read the detailed description
Coronary artery disease and the benefit of bypasses:
Despite considerable advances in medicine, cardiovascular diseases remain the number one cause of death globally, primarily consequence of myocardial infarction (MI). Although widely used in stable CAD, percutaneous coronary intervention (PCI) has not been shown to reduce the incidence of myocardial infarction or death. In contrast, coronary artery bypass grafting (CABG) significantly reduced rates of death and myocardial infarction compared to PCI. Similarly, coronary collaterals exert a protective effect by providing an alternative source of blood flow to a myocardial territory potentially affected by an acute coronary occlusion. Coronary collaterals represent pre-existing inter-arterial anastomoses and as such are the natural counter-part of surgically created bypasses. Sufficient coronary collaterals have been shown to confer a significant benefit in terms of overall mortality and cardiovascular events. In this regard, the concept of augmenting coronary collateral function as an alternative treatment strategy to alter the course of CAD, as well as to control symptoms, is attractive.
Durable promotion of coronary collateral circulation:
While a multitude of interventions has been shown to be effective in collateral growth promotion, so far, the effect of current interventions is only temporary and therefore recurrent application is necessary to sustain the level of collaterals. However, before the advent of coronary artery bypass grafting, permanent augmentation of coronary collateral supply by a single structural modification has already been attempted. Bilateral ligation of the internal mammary arteries (IMA) was performed in CAD patients to alleviate angina pectoris and electrocardiographic (ECG) signs of ischemia. The prevalent in vivo function of natural IMA-to-coronary artery bypasses and their anti-ischemic effect has - for the first time - been recently demonstrated by our research group. Levels of collateral function and myocardial ischemia were determined during two coronary balloon occlusions, the first with, the second without distal IMA balloon occlusion. Coronary collateral function, was consistently increased in the presence vs the absence of distal ipsilateral IMA balloon occlusion. These findings were corroborated by the observed reduction in ischemia. Conversely, with distal contralateral IMA occlusion, collateral function and ECG signs of ischemia remained unchanged. The acute functional changes observed in response to temporary distal IMA balloon occlusion are expected to result in larger chronic structural adaptations of the IMA-to-coronary-artery connections when the distal IMA is permanently occluded. In contrast to the previously employed arteriogenic approaches in humans, the attractiveness of such an intervention lies in the potential durability of the effect.
In a first step, catheter-based IMA occlusion ought to be conceptually investigated in the setting of the less frequently grafted right IMA among patients with ischemia in the right coronary artery territory.
- Conditions
- Circulation, Collateral, Coronary Artery Disease, Internal Mammary-Coronary Artery Anastomosis, Ischemia
- Being tested
- Amplatzer vascular plug
- Keywords
- Circulation, Collateral, Coronary Artery Disease, Internal Mammary-Coronary Artery Anastomosis, Ischemia
- Medical subject headings
- Coronary Artery Disease, Ischemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Amplatzer vascular plugDevice
| Study group | Role | What they receive |
|---|---|---|
| Interventional Study Arm | Experimental | In the presence of a significant right coronary artery stenosis, catheter-based occlusion of the right IMA distal to the take-off of the pericardio-phrenic branch is performed at baseline using a dedicated occlusion device (Amplatzer vascular plug). Receives: Device: Amplatzer vascular plug |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline in right coronary Collateral Flow Index (CFI)
Change from baseline in right coronary Collateral Flow Index (CFI) at follow-up (week 6) vs baseline
Measured: Follow-up (week 6)
Secondary outcomes (4)
Change from baseline in left coronary CFI
Change from baseline in left coronary CFI at follow-up (week 6) vs baseline
Measured: Follow-up (week 6)
Change from baseline in intracoronary and surface ECG ST-segment shift during temporary right and left coronary balloon occlusion
Change from baseline in intracoronary and surface ECG ST-segment shift during temporary right and left coronary balloon occlusion at follow-up (week 6) vs baseline
Measured: Follow-up (week 6)
Number of patients with angiographic visibility of right IMA-to-coronary anastomoses
Angiographic visibility of right IMA-to-coronary anastomoses at follow-up
Measured: Follow-up (week 6)
Number of patients with catheter-based permanent right IMA occlusion
Measured: Baseline, Follow-up (week 6)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jun 2015 (estimated)
- Study startDec 2014
- Primary completionMar 2016
- Study completionApr 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Circulation, CollateralStudies of the same condition, open and under way.
- More trials run by Insel Gruppe AG, University Hospital BernThe 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 1/2
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Insel Gruppe AG, University Hospital Bern
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Seiler Christian, MD, Prof, Principal investigator, Bern University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02475408
- Sponsor's protocol ID
- SNCTP000000901
- Acronym
- IMAO
- Status last verified
- Jun 2015
- First submitted
- 5 Jan 2015
- Last updated
- 12 May 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Stoller M, de Marchi SF, Seiler C. Function of natural internal mammary-to-coronary artery bypasses and its effect on myocardial ischemia. Circulation. 2014 Jun 24;129(25):2645-52. doi: 10.1161/CIRCULATIONAHA.114.008898. Epub 2014 Apr 17.
PubMed 24744276Moberg A. Anastomoses between extracardiac vessels and coronary arteries. II. Via internal mammary arteries. Post-mortem angiographic study. Acta Radiol Diagn (Stockh). 1967 May;6(3):263-72. doi: 10.1177/028418516700600306. No abstract available.
PubMed 6025072BLAIR CR, ROTH RF, ZINTEL HA. Measurement of coronary artery blood-flow following experimental ligation of the internal mammary artery. Ann Surg. 1960 Aug;152(2):325-9. doi: 10.1097/00000658-196008000-00018. No abstract available.
PubMed 13801236Stoller M, Seiler C. Effect of Permanent Right Internal Mammary Artery Closure on Coronary Collateral Function and Myocardial Ischemia. Circ Cardiovasc Interv. 2017 Jun;10(6):e004990. doi: 10.1161/CIRCINTERVENTIONS.116.004990.
PubMed 28566292
Study at a glance
From the registry record, last updated by the sponsor on 12 May 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Permanent Internal Mammary Artery Occlusion on Extracardiac Coronary Collateral Supply
- ClinicalTrials.gov ID
- NCT02475408
- Acronym / sponsor ID
- IMAO / SNCTP000000901
- Conditions
- Circulation, Collateral, Coronary Artery Disease, Internal Mammary-Coronary Artery Anastomosis, Ischemia
- Keywords
- Circulation, Collateral, Coronary Artery Disease, Internal Mammary-Coronary Artery Anastomosis, Ischemia
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Insel Gruppe AG, University Hospital BernUniversity, hospital or other
- Study start
- Dec 2014
- Primary completion
- Mar 2016 (actual)
- Study completion
- Apr 2016 (actual)
- First posted
- 18 Jun 2015 (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.
Coronary artery disease and the benefit of bypasses:
Despite considerable advances in medicine, cardiovascular diseases remain the number one cause of death globally, primarily consequence of myocardial infarction (MI). Coronary collaterals exert a protective effect by providing an alternative source of blood flow to a myocardial territory potentially affected by an acute coronary occlusion. Coronary collaterals represent pre-existing inter-arterial anastomoses and as such are the natural counter-part of surgically created bypasses. Sufficient coronary collaterals have been shown to confer a significant benefit in terms of overall mortality and cardiovascular events. In this regard, the concept of augmenting coronary collateral function as an alternative treatment strategy to alter the course of CAD, as well as to control symptoms, is attractive.
Durable promotion of coronary collateral circulation:
Before the advent of coronary artery bypass grafting, permanent augmentation of coronary collateral supply by a single structural modification has already been attempted. Bilateral ligation of the internal mammary arteries (IMA) was performed in CAD patients to alleviate angina pectoris and electrocardiographic (ECG) signs of ischemia. The prevalent in vivo function of natural IMA-to-coronary artery bypasses and their anti-ischemic effect has - for the first time - been recently demonstrated by our research group. The acute functional changes observed in response to temporary distal IMA balloon occlusion are expected to result in larger chronic structural adaptations of the IMA-to-coronary-artery connections when the distal IMA is permanently occluded. In contrast to the previously employed arteriogenic approaches in humans, the attractiveness of such an intervention lies in the potential durability of the effect.
In a first step, catheter-based IMA occlusion ought to be conceptually investigated in the setting of the less frequently grafted right IMA among patients with ischemia in the right coronary artery territory.
Detailed description
Coronary artery disease and the benefit of bypasses:
Despite considerable advances in medicine, cardiovascular diseases remain the number one cause of death globally, primarily consequence of myocardial infarction (MI). Although widely used in stable CAD, percutaneous coronary intervention (PCI) has not been shown to reduce the incidence of myocardial infarction or death. In contrast, coronary artery bypass grafting (CABG) significantly reduced rates of death and myocardial infarction compared to PCI. Similarly, coronary collaterals exert a protective effect by providing an alternative source of blood flow to a myocardial territory potentially affected by an acute coronary occlusion. Coronary collaterals represent pre-existing inter-arterial anastomoses and as such are the natural counter-part of surgically created bypasses. Sufficient coronary collaterals have been shown to confer a significant benefit in terms of overall mortality and cardiovascular events. In this regard, the concept of augmenting coronary collateral function as an alternative treatment strategy to alter the course of CAD, as well as to control symptoms, is attractive.
Durable promotion of coronary collateral circulation:
While a multitude of interventions has been shown to be effective in collateral growth promotion, so far, the effect of current interventions is only temporary and therefore recurrent application is necessary to sustain the level of collaterals. However, before the advent of coronary artery bypass grafting, permanent augmentation of coronary collateral supply by a single structural modification has already been attempted. Bilateral ligation of the internal mammary arteries (IMA) was performed in CAD patients to alleviate angina pectoris and electrocardiographic (ECG) signs of ischemia. The prevalent in vivo function of natural IMA-to-coronary artery bypasses and their anti-ischemic effect has - for the first time - been recently demonstrated by our research group. Levels of collateral function and myocardial ischemia were determined during two coronary balloon occlusions, the first with, the second without distal IMA balloon occlusion. Coronary collateral function, was consistently increased in the presence vs the absence of distal ipsilateral IMA balloon occlusion. These findings were corroborated by the observed reduction in ischemia. Conversely, with distal contralateral IMA occlusion, collateral function and ECG signs of ischemia remained unchanged. The acute functional changes observed in response to temporary distal IMA balloon occlusion are expected to result in larger chronic structural adaptations of the IMA-to-coronary-artery connections when the distal IMA is permanently occluded. In contrast to the previously employed arteriogenic approaches in humans, the attractiveness of such an intervention lies in the potential durability of the effect.
In a first step, catheter-based IMA occlusion ought to be conceptually investigated in the setting of the less frequently grafted right IMA among patients with ischemia in the right coronary artery territory.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Interventional Study Arm | Experimental | Device: Amplatzer vascular plugIn the presence of a significant right coronary artery stenosis, catheter-based occlusion of the right IMA distal to the take-off of the pericardio-phrenic branch is performed at baseline using a dedicated occlusion device (Amplatzer vascular plug). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age > 18 years
- Referred for elective coronary angiography
- Written informed consent to participate in the study
- Significant stenosis of right coronary artery (FFR ≤0.80)
Key exclusion criteria (10 listed)
- Acute coronary syndrome; unstable cardiopulmonary conditions, unstable angina pectoris
- Collateral flow index of right IMA <0.25
- Severe cardiac valve disease
- Congestive heart failure NYHA III-IV
- Prior coronary artery bypass surgery / prior cardiac surgery
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 |
|---|---|---|
| Amplatzer vascular plug | Device | Interventional Study Arm |
Primary outcome
Change from baseline in right coronary Collateral Flow Index (CFI)
Time frame: Follow-up (week 6)
Change from baseline in right coronary Collateral Flow Index (CFI) at follow-up (week 6) vs baseline
4 secondary outcomes
Change from baseline in left coronary CFI
Time frame: Follow-up (week 6)
Change from baseline in intracoronary and surface ECG ST-segment shift during temporary right and left coronary balloon occlusion
Time frame: Follow-up (week 6)
Number of patients with angiographic visibility of right IMA-to-coronary anastomoses
Time frame: Follow-up (week 6)
Number of patients with catheter-based permanent right IMA occlusion
Time frame: Baseline, Follow-up (week 6)
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 12 May 2016.
- Background: PubMed 24744276Stoller M, de Marchi SF, Seiler C. Function of natural internal mammary-to-coronary artery bypasses and its effect on myocardial ischemia. Circulation. 2014 Jun 24;129(25):2645-52. doi: 10.1161/CIRCULATIONAHA.114.008898. Epub 2014 Apr 17.
- Background: PubMed 6025072Moberg A. Anastomoses between extracardiac vessels and coronary arteries. II. Via internal mammary arteries. Post-mortem angiographic study. Acta Radiol Diagn (Stockh). 1967 May;6(3):263-72. doi: 10.1177/028418516700600306. No abstract available.
- Background: PubMed 13801236BLAIR CR, ROTH RF, ZINTEL HA. Measurement of coronary artery blood-flow following experimental ligation of the internal mammary artery. Ann Surg. 1960 Aug;152(2):325-9. doi: 10.1097/00000658-196008000-00018. No abstract available.
- Derived from this study: PubMed 28566292Stoller M, Seiler C. Effect of Permanent Right Internal Mammary Artery Closure on Coronary Collateral Function and Myocardial Ischemia. Circ Cardiovasc Interv. 2017 Jun;10(6):e004990. doi: 10.1161/CIRCINTERVENTIONS.116.004990.
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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.
Seiler Christian, MD, Prof principal investigator
Bern University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Amplatzer vascular plug in people with Circulation, Collateral and Coronary Artery Disease, run by Insel Gruppe AG, University Hospital Bern at 1 site in Switzerland.
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 4 inclusion and 10 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 12 May 2016. 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 Switzerland. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 from baseline in right coronary Collateral Flow Index (CFI) (time frame: Follow-up (week 6)). 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 NCT02475408, which also lists 4 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 12 May 2016.