Clinical Efficacy of Permanent Internal Mammary Artery Occlusion in Stable Coronary Artery Disease

NCT03710070 | Completed DMC

• 1 other identifier: 2018-01480
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

Cardiovascular diseases remain the number one cause of death globally, primarily consequence of myocardial infarction. Although widely used in stable coronary artery disease (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 reduces rates of death and myocardial infarction compared to PCI, but at a higher rate of stroke. 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. 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, repeated application is necessary to sustain the level of collaterals. The prevalent in vivo function of natural internal mammary arteries (IMA)-to-coronary artery bypasses and their anti-ischemic effect has been recently demonstrated by the investigators' research group. Levels of collateral function and myocardial ischemia were determined in a prospective, open-label clinical trial of permanent IMA device occlusion. In this study, coronary collateral function, has been shown to be augmented in the presence vs the absence of distal permanent ipsilateral IMA occlusion. These findings have been corroborated by the observed reduction in ischemia in the intracoronary ECG. Coronary functional changes observed in response to permanent distal IMA occlusion have so far, not been related to clinical outcome parameters. Therefore, a controlled, randomized, double-blind comparison of clinical efficacy between a group of patients receiving permanent IMA occlusion vs. a sham-procedure will be consequently performed. Since single antianginal agents have been demonstrated to increase exercise time in comparison to placebo, an improvement of the physical performance due to the increased blood flow by the permanent distal IMA occlusion is expected.

Conditions

Coronary Artery Disease; Internal Mammary-Coronary Artery Anastomosis; Ischemia; Circulation, Collateral

Keywords

Collateral Flow Index; Permanent Internal Mammary Artery Occlusion

Outcome Measures

Primary Outcomes (1)

• Treadmill exercise time increment

  Treadmill exercise time at follow-up minus treadmill exercise time at baseline exam (difference measured in seconds)

  Follow-up (week 6)

Secondary Outcomes (6)

• Angina pectoris

  Follow-up (week 6)

• Collateral flow index

  Follow-up (week 6)

• Occlusive intracoronary ECG ST-segment shift

  Follow-up (week 6)

• Fractional flow reserve

  Follow-up (week 6)

• Seattle Angina Questionnaire scores

  Follow-up (week 6)

Study Arms (2)

Intervention

EXPERIMENTAL

In the presence of a significant coronary artery stenosis and randomization to the intervention group: Catheter-based permanent occlusion of the ipsilateral (to the culprit coronary lesion) IMA will be performed at the projected height of inferior vena cava confluence and right atrium using a dedicated occlusion device (Amplatzer vascular plug 4, CE0086).

Device: Amplatzer vascular plug 4

Sham-Control

SHAM COMPARATOR

In the presence of a significant coronary artery stenosis, and randomization to the sham-procedure: IMA will be selectively intubated using an appropriate catheter. Angiography of the IMA and the pericardiacophrenic branch will be performed.

Other: Sham Control

Interventions

Amplatzer vascular plug 4 DEVICE

See above

Intervention

Sham Control OTHER

Angiography of the IMA without occlusion

Sham-Control

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Chronic stable 1- to 3-vessel CAD
• Written informed consent to participate in the study

You may not qualify if:

• Absence of at least one coronary stenotic lesion ≥50% diameter narrowing.
• Acute coronary syndrome; unstable cardiopulmonary condition, unstable angina pectoris
• Severe valvular heart disease
• Congestive heart failure NYHA III-IV
• Prior coronary artery bypass surgery / prior cardiac surgery
• CAD best treated by coronary artery bypass grafting
• Prior Q-wave myocardial infarction in the vascular territory undergoing collateral function measurement
• Severe renal or hepatic failure
• Women of childbearing age

Sponsors & Collaborators

• Insel Gruppe AG, University Hospital Bern: lead

Study Sites (1)

University Hospital Inselspital, Bern

Bern, Switzerland

Location

Related Publications (2)

• 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.

  PMID: 24744276 BACKGROUND

• Stoller 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.

  PMID: 28566292 BACKGROUND

MeSH Terms

Conditions

Coronary Artery Disease; Ischemia

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Christian Seiler, Prof

  Sponsor-Investigator

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 11, 2018
• First Posted: October 17, 2018
• Study Start: March 8, 2019
• Primary Completion: April 1, 2022
• Study Completion: April 1, 2022
• Last Updated: February 14, 2023

Record last verified: 2023-02

Locations

CH (1)