Clinical trial NCT03115580: Side Branch FFR After Provisional Stenting
Official title: Optical Coherence Tomography Predictors of Functionally Significant Side Branch Compromise After Provisional Main Vessel Stenting In Calcific Coronary Artery Disease Assessed by Fractional Flow Reserve
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Coronary Artery Disease
Lead sponsor: Icahn School of Medicine at Mount Sinai
Sponsor class: OTHER
First posted: 2017-04-14
Enrollment: 71
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to predict any changes in the side branch after stenting the main branch blood vessel using three dimensional intravascular images. (Frequency domain optical coherence tomography FD OCT).

Optical coherence tomography (OCT) is an established medical imaging technique that uses light to capture high-resolution, three-dimensional images of blood vessels. These images will be used before and after implanting the stent in the main blood vessel. Fractional Flow Reserve (FFR) test, which makes it possible for the interventional cardiologist to calculate blood flow across an area of a coronary artery, will be done after stenting and will help to determine if there are any changes in the side branch blood flow.

Detailed description: Coronary artery bifurcation lesion is a common lesion subset in PCI accounting for 15-20% of the total number of interventions. Treatment of coronary artery bifurcation lesions represents a challenging area in interventional cardiology. When compared with non-bifurcation interventions, bifurcation interventions have a lower rate of procedural success, higher procedural costs, longer hospitalization and a higher clinical and angiographic restenosis. Factors contributing to this adverse outcome include limitations of angiography in assessment of side-branch (SB) disease severity and the lack of established angiographic predictors of SB patency and lumen compromise. Better understanding of the underlying plaque morphology and plaque composition may facilitate more effective treatment of bifurcation lesions.

Intravascular imaging has provided new understanding of mechanisms associated with SB compromise following bifurcation PCI. Plaque shift has been traditionally considered as the principal mechanism for side-branch compromise after main vessel intervention. Rotational atherectomy(RA) has been advocated for the treatment of bifurcation lesions, since it can effectively remove plaque with minimal injury to adjacent normal arterial segments and potentially reduce plaque shifting, the "snow plow" effect. Intravascular ultrasound (IVUS) has been used for guidance in bifurcation lesions, aiding the visualization of plaque morphology at the main vessel and the side-branches and helping the selection of stent size and length as well as the selection of stenting strategy. However, due to the low spatial resolution of IVUS, all attempts for three-dimensional visualization have only focused on visualization of the luminal contour and not on the vessel morphology or the vessel-stent interaction. Optical coherence tomography (OCT) has \~10 times higher resolution than IVUS, which allows precise evaluation of the microstructure of the vessel wall including lipid pool, fibrous cap, calcification, and thrombus. OCT has been shown to constitute a valuable tool for PCI guidance and also the utility of three-dimensional (3D) renderings for assessing the mechanism of side-branch compromise following intervention in bifurcation lesions. The recent development of OCT with online 3D reconstruction allows the operator to obtain a 3D visualization of the lesion and may provide a unique tool for guidance during complex bifurcation PCI and potentially improve stenting results. 3D OCT has been used to visualize jailed side branches after implantation of bioresorbable scaffolds in the main branch and develop a new classification system based on the number of SB compartments. In addition, its potential clinical application in guiding the rewiring of the distal compartment of the SB ostium (jailed with stent struts after MB stenting) to minimize the risk of floating struts was demonstrated It is important to note that while OCT, 3D-OCT, and 3D-QCA (such as that used in the ORBID trial) are imaging modalities that can be used to answer important research questions, their wide-spread adoption in daily clinical practice has been very limited. Intravascular ultrasound (IVUS) is used more frequently as part of a PCI guidance strategy in daily clinical practice.

Fractional flow reserve (FFR) is a pressure-derived, lesion specific index used to determine the functional significance of coronary artery stenosis. Several studies showed that FFR is a safe and feasible method to assess the significance of an ostial SB stenosis after provisional stenting. Quantitative coronary angiography (QCA) has been shown to be unreliable in assessing the functional significance of SB after stent implantation in MV (the area under the curve 0.64, 41.5% sensitivity and 83.1% specificity) suggesting that treatment decisions for jailed SB should not be based on angiographic findings alone. A recent report demonstrated a better ability of post-PCI 3D-OCT to predict the functional significance for SB ostial lesions caused by a jailed SB outcome.

A previous study (ORBID) of 30 patients was done at Mount Sinai Hospital and aimed to identify the predictors of side branch (SB) ostial stenosis developed after provisional stenting of the main vessel (MV) using Optical Coherence Tomography (OCT). The study Showed that High lipid content of the MV lesion and a contralateral location of lipid in the bifurcation area may contribute to SBOS after provisional stenting.

The objective of this study is to analyze the incidence of SB compromise after provisional main vessel stenting in calcified bifurcation lesions of CAD patients, determine the incidence and OCT predictors of functionally significant SB stenosis defined as FFR ≤ 0.8 and to compare the FFR values with 3D-OCT measurements of jailed SB ostium after MV stenting.

Stable CAD patients with bifurcation lesions in whom provisional stenting strategy is planned, who have moderate or severe calcification in the main vessel lesion identified by angiography, SB stenosis 30-70% and SB reference diameter \> 2mm will be enrolled in the study.

Moderate calcification will be defined as radiopaque density observed only during the cardiac cycle and typically involving only one side of the vascular wall, and severe calcification will be defined as radiopaque density noted without cardiac motion prior to contrast injection and involving both sides of the arterial wall. After completion of diagnostic angiogram and confirmation of subject eligibility, subjects will be randomly assigned to Rotational Atherectomy (RA) or Cutting Balloon Angioplasty (CBA)/Percutaneous Transluminal Coronary Angioplasty (PTCA) group in a 1:1 fashion.

Patients in both groups will undergo PCI with stent implantation according to current standards of care. Lesion preparation including lesion pre-dilation, scoring or sculpting balloon angioplasty, and use of atherectomy and protection devices will be performed at the operator's discretion, followed by MV stenting. The operator will also decide in both groups about the length and size of the implanted stent. Procedural optimization, such as post-dilation or additional stent implantation will be performed based only on the angiographic findings, according to the discretion of the operator.

Eligibility criteria: Inclusion Criteria:

* All patients over 18 years of age presenting with stable coronary artery disease.
* Patients must have a clinical indication for coronary intervention.
* Creatinine Kinase Myocardial-Band Isoenzyme (CK-MB) must be less than or equal to the upper limit of lab normal (ULN) value within eight hours prior to the procedure.
* The target lesion must be a de novo calcified bifurcation coronary lesion that hasn't been previously treated with any interventional procedure for which provisional main vessel stenting strategy is planned after reviewing angiogram.
* The target vessel must be a native coronary artery with

  1. stenosis ≥70% and \<100%, or
  2. Stenosis ≥50% and \<70% with evidence of clinical ischemia via positive stress test, or FFR ≤ 0.8, or IVUS or OCT minimal lumen area ≤ 4.0 mm2.
* The target lesion should have SB DS 30 - 70%.
* The target main vessel reference diameter must be ≥2.5 mm and ≤ 4.0 mm.
* The SB reference diameter must be \> 2 mm by coronary angiogram.
* The target vessel must have a Thrombolysis in Myocardial Infarction (TIMI) flow grade 3 at baseline.

Exclusion Criteria:

* Patients with ostial left main artery lesions or ostial right coronary artery lesions
* Female patients with child bearing potential not taking adequate contraceptives or currently breastfeeding
* Known allergy to acetylsalicylic acid or clopidogrel.
* Planned surgery within 12 months.
* History of bleeding diathesis
* Major surgery within 15 days
* Life expectancy \< 12 months.
* Patients with kidney dysfunction (CrCl\<30)

Primary outcomes:
measure: Number of Participants With Side Branch Compromise
timeFrame: Day 1
Secondary outcomes:
measure: Number of Participants With SB Dissection
timeFrame: Day 1
measure: Number of Participants With TIMI < 3
timeFrame: Day 1
measure: Number of Participants With SB DS >70%
timeFrame: Day 1
measure: Number of Participants With FFR Device Success
timeFrame: Day 1
measure: Number of Patients With FFR Wire Workhorse Capability
timeFrame: Day 1
Other outcomes:
Locations:
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai and the Mount Sinai Hospital
state: New York
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: Annapoorna Kini, MD, MRCO, FACC
role: PRINCIPAL_INVESTIGATOR
References: