Atherosclerosis, Coronary Artery Disease, Coronary Stenosis, NSTEMI - Non-ST Segment Elevation Myocardial Infarction (MI), STEMI, STEMI - ST Elevation Myocardial Infarction
Conditions
Keywords
ABT-CIP-10233, ILUMIEN OPTIS OCT Imaging System, Dragonfly, Optical Coherence Tomography (OCT), Coronary Stent IMplantation, Angiography
Brief summary
The objective of this prospective, single-blind clinical investigation is to demonstrate the superiority of an Optical Coherence Tomography (OCT)-guided stent implantation strategy as compared to an angiography-guided stent implantation strategy in achieving larger post-PCI lumen dimensions and improving clinical cardiovascular outcomes in patients with high-risk clinical characteristics and/or with high-risk angiographic lesions.
Interventions
Stent implantation in high-risk or complex lesions in patients with coronary artery disease using OCT guidance
Stent implantation in high-risk or complex lesions in patients with coronary artery disease using angiography guidance
Sponsors
Abbott
Abbott Medical Devices
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
(all must be present) 1. Subject must be at least 18 years of age. 2. Subject must have evidence of myocardial ischemia (e.g., stable angina, silent ischemia (ischemia in the absence of chest pain or other anginal equivalents), unstable angina, or acute myocardial infarction) suitable for elective PCI. 3. Patients undergoing planned XIENCE stent implantation during a clinically indicated PCI procedure meeting one or more of the following criteria: A) High clinical-risk, defined as; i. Medication-treated diabetes mellitus, AND/OR B) High angiographic-risk lesion(s), with at least one target lesion in each target vessel planned for randomization meeting at least one of the following criteria; i. Target lesion is the culprit lesion responsible for either: * NSTEMI, defined as a clinical syndrome consistent with an acute coronary syndrome and a minimum troponin of 1 ng/dL (may or may not have returned to normal), OR * STEMI \>24 hours from the onset of ischemic symptoms ii. long or multiple lesions (defined as intended total stent length in any single target vessel ≥28 mm), Note: For a long target lesion, this would permit treatment by a single long stent or overlapping stents. Note: For up to two target lesions located in a single target vessel and treated with non-overlapping stents, they may be located in a continuous vessel or split up between a main vessel and a side branch. iii. bifurcation intended to be treated with 2 planned stents (i.e. in both the main branch and side branch), and where the planned side branch stent is ≥ 2.5 mm in diameter by angiographic visual estimation. iv. angiographic severe calcification (defined as angiographically visible calcification on both sides of the vessel wall in the absence of cardiac motion), v. chronic total occlusion (CTO) (enrolment and randomization in this case performed only after successful antegrade wire escalation crossing and pre-dilatation) vi. in-stent restenosis of diffuse or multi-focal pattern. Lesion must be at or within the existing stent margin(s) and have angiographically visually-assessed DS ≥70% or DS ≥50% with non-invasive or invasive evidence of ischemia 4. All target lesions (those lesions to be randomized) must have a visually estimated or quantitatively assessed %DS of either ≥70%, or ≥50% plus one or more of the following: an abnormal functional test (e.g. fractional flow reserve, stress test) signifying ischemia in the distribution of the target lesion(s) or biomarker positive ACS with plaque disruption or thrombus. Note: For purposes of study eligibility, a minimum troponin of 1 ng/dL at the time of screening will be considered biomarker positive. 5. All target lesions must be planned for treatment with only ≥2.5 mm and ≤3.5 mm stents and post-dilatation balloons based on pre-PCI angiographic visual estimation. 6. No more than 2 target lesions requiring PCI are present in any single vessel., and no more than 2 target vessels are allowed. Thus, up to 4 randomized target lesions per patient in a maximum of 2 target vessels are allowed, including branches. The intended target lesions will be declared just prior to randomization. Note: A lesion is defined as any segment(s) of the coronary tree, no matter how long, which is planned to be covered with one contiguous length of stent, whether single or overlapped. A bifurcation counts as a single lesion even if the side branch is planned to be treated. Note: All lesions in a randomized target vessel that are intended to be treated by PCI are designated as target lesions, and at least one target lesion in each randomized target vessel must meet angiographic high-risk inclusion criteria summarized above in 3B). The only exception is for patients who qualify for the trial on the basis of medication-treated diabetes, in which case no target lesion is required to meet angiographic high-risk inclusion criteria. 7. All target lesions intended to be treated by PCI in the target vessel are amenable to OCT-guided PCI. Example: If a qualifying angiographic high-risk lesion is in the proximal LAD, and there is a second target lesion in the distal LAD which is a focal lesion not otherwise meeting high-risk criteria, both the proximal LAD and distal LAD lesions must be amenable to OCT (e.g. no excessive tortuosity or calcification precluding delivering the OCT catheter), and each lesion must undergo OCT-guided stenting. Otherwise the vessel should be excluded from randomization. 8. Subject must provide written Informed Consent prior to any study related procedure.
Exclusion criteria
(none may be present) Clinical
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Imaging Outcome (Powered): Minimal Stent Area (MSA) | Final Post-PCI Measurement (average of 24 hours). | Minimal Stent Area (per target lesion basis) assessed by OCT in each randomized arm, measured at an independent OCT core laboratory blinded to imaging modality assignment. |
| Number of Participants With Target Vessel Failure (TVF) | At 2 years | Time-to-first event rate of the composite outcome of cardiac death, target vessel myocardial infarction (TV-MI), or ischemia-driven target vessel revascularization (ID-TVR), will be assessed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Target Vessel Failure (TVF) Excluding Periprocedural MI (Powered) | At 2 years | Time-to-first event rate of composite outcome of cardiac death, target vessel-related spontaneous myocardial infarction, or ischemia-driven target vessel revascularization (ID-TVR) will be assessed. |
| The Results of Adjudicated Clinical Outcomes to 2 Years in the Randomized Population | 2 years | The results of adjudicated clinical outcomes to 2 years in the randomized population by Kaplan-Meier assessment. |
| The Number of Participants With Stent Thrombosis | 2 years | The results of adjudicated clinical outcomes to 2 years in the randomized population by Kaplan-Meier assessment. |
Countries
Australia, Belgium, Canada, Denmark, France, Germany, Hong Kong, India, Italy, Japan, Netherlands, New Zealand, Portugal, Singapore, Spain, Sweden, Switzerland, Taiwan, United Kingdom, United States
Participant flow
Recruitment details
The first randomized subject was enrolled in the study on May 17, 2018. The trial completed enrollment on December 29, 2020 with a total of 2487 randomized subjects. The randomized subjects, who were enrolled at 80 sites in 18 countries, were comprised of 1233 subjects assigned to the OCT-guided PCI arm and 1254 subjects in the angiography-guided PCI arm.
Pre-assignment details
In this study, the total number of randomized participants were 2487, out of which 1233 were assigned to OCT guidance and 1254 were assigned to angiography guidance.
Participants by arm
| Arm | Count |
|---|---|
| Coronary PCI Guided by OCT Intervention = Coronary stenting with planned drug eluting stent (DES).
Stenting will be performed with OCT guidance according to the algorithm described in the protocol. OCT imaging is required pre and post stent implantation.
At the end of the procedure, a final OCT imaging run must be performed.
Coronary PCI guided by OCT: Stent implantation in high-risk or complex lesions in patients with coronary artery disease using OCT guidance | 1,233 |
| Coronary PCI Guided by Angiography Intervention = Coronary stenting with planned drug eluting stent (DES).
Stenting will be performed with angiography guidance according to local standard practice.
At the end of the procedure, a blinded OCT shall be performed to document final stent dimensions and results.
Coronary PCI guided by Angiography: Stent implantation in high-risk or complex lesions in patients with coronary artery disease using angiography guidance | 1,254 |
| Total | 2,487 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 30 | 44 |
| Overall Study | Lost to Follow-up | 5 | 7 |
| Overall Study | Other Reasons | 3 | 8 |
| Overall Study | Withdrawal by Subject | 6 | 11 |
Baseline characteristics
| Characteristic | Total | Coronary PCI Guided by Angiography | Coronary PCI Guided by OCT |
|---|---|---|---|
| Age, Continuous | 65.6 Years STANDARD_DEVIATION 10.4 | 65.7 Years STANDARD_DEVIATION 10.3 | 65.5 Years STANDARD_DEVIATION 10.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 128 Participants | 67 Participants | 61 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1737 Participants | 867 Participants | 870 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 622 Participants | 320 Participants | 302 Participants |
| Hypertension req. Medication | 1808 participants | 928 participants | 880 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 7 Participants | 4 Participants | 3 Participants |
| Race (NIH/OMB) Asian | 308 Participants | 156 Participants | 152 Participants |
| Race (NIH/OMB) Black or African American | 85 Participants | 43 Participants | 42 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 3 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 12 Participants | 6 Participants | 6 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 569 Participants | 298 Participants | 271 Participants |
| Race (NIH/OMB) White | 1503 Participants | 744 Participants | 759 Participants |
| Region of Enrollment Canada | 108 participants | 55 participants | 53 participants |
| Region of Enrollment Europe | 1093 participants | 553 participants | 540 participants |
| Region of Enrollment Pacifica | 377 participants | 188 participants | 189 participants |
| Region of Enrollment United States | 909 participants | 458 participants | 451 participants |
| Sex: Female, Male Female | 563 Participants | 298 Participants | 265 Participants |
| Sex: Female, Male Male | 1924 Participants | 956 Participants | 968 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 33 / 1,233 | 44 / 1,254 |
| other Total, other adverse events | 71 / 1,233 | 73 / 1,254 |
| serious Total, serious adverse events | 405 / 1,233 | 411 / 1,254 |
Outcome results
Primary
Imaging Outcome (Powered): Minimal Stent Area (MSA)
Minimal Stent Area (per target lesion basis) assessed by OCT in each randomized arm, measured at an independent OCT core laboratory blinded to imaging modality assignment.
Time frame: Final Post-PCI Measurement (average of 24 hours).
Population: The number of participants analyzed includes subjects who were available at that time of analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Coronary PCI Guided by OCT | Imaging Outcome (Powered): Minimal Stent Area (MSA) | 5.72 mm^2 | Standard Deviation 2.04 |
| Coronary PCI Guided by Angiography | Imaging Outcome (Powered): Minimal Stent Area (MSA) | 5.36 mm^2 | Standard Deviation 1.87 |
p-value: <0.0001Linear mixed model
Primary
Number of Participants With Target Vessel Failure (TVF)
Time-to-first event rate of the composite outcome of cardiac death, target vessel myocardial infarction (TV-MI), or ischemia-driven target vessel revascularization (ID-TVR), will be assessed.
Time frame: At 2 years
Population: The number of participants analyzed includes subjects who were available at that time of analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Coronary PCI Guided by OCT | Number of Participants With Target Vessel Failure (TVF) | 88 participants who experienced the event |
| Coronary PCI Guided by Angiography | Number of Participants With Target Vessel Failure (TVF) | 99 participants who experienced the event |
p-value: 0.2487A Cox regression model
Secondary
Number of Participants With Target Vessel Failure (TVF) Excluding Periprocedural MI (Powered)
Time-to-first event rate of composite outcome of cardiac death, target vessel-related spontaneous myocardial infarction, or ischemia-driven target vessel revascularization (ID-TVR) will be assessed.
Time frame: At 2 years
Population: The number of participants analyzed includes subjects who were available at that time of analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Coronary PCI Guided by OCT | Number of Participants With Target Vessel Failure (TVF) Excluding Periprocedural MI (Powered) | 74 participants who experienced the event |
| Coronary PCI Guided by Angiography | Number of Participants With Target Vessel Failure (TVF) Excluding Periprocedural MI (Powered) | 82 participants who experienced the event |
p-value: 0.2952A Cox regression model
Secondary
The Number of Participants With Stent Thrombosis
The results of adjudicated clinical outcomes to 2 years in the randomized population by Kaplan-Meier assessment.
Time frame: 2 years
Population: The number of participants analyzed includes subjects who were available at that time of analysis
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Coronary PCI Guided by OCT | The Number of Participants With Stent Thrombosis | Definite | 5 participants |
| Coronary PCI Guided by OCT | The Number of Participants With Stent Thrombosis | Definite/Probable | 6 participants |
| Coronary PCI Guided by Angiography | The Number of Participants With Stent Thrombosis | Definite | 14 participants |
| Coronary PCI Guided by Angiography | The Number of Participants With Stent Thrombosis | Definite/Probable | 17 participants |
Secondary
The Results of Adjudicated Clinical Outcomes to 2 Years in the Randomized Population
The results of adjudicated clinical outcomes to 2 years in the randomized population by Kaplan-Meier assessment.
Time frame: 2 years
Population: The number of participants analyzed includes subjects who were available at that time of analysis
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Coronary PCI Guided by OCT | The Results of Adjudicated Clinical Outcomes to 2 Years in the Randomized Population | TLF | 76 participants |
| Coronary PCI Guided by OCT | The Results of Adjudicated Clinical Outcomes to 2 Years in the Randomized Population | All Death | 32 participants |
| Coronary PCI Guided by OCT | The Results of Adjudicated Clinical Outcomes to 2 Years in the Randomized Population | All MI | 57 participants |
| Coronary PCI Guided by OCT | The Results of Adjudicated Clinical Outcomes to 2 Years in the Randomized Population | All Revascularization | 112 participants |
| Coronary PCI Guided by OCT | The Results of Adjudicated Clinical Outcomes to 2 Years in the Randomized Population | All Death, All MI, All Revascularization (DMR) | 171 participants |
| Coronary PCI Guided by OCT | The Results of Adjudicated Clinical Outcomes to 2 Years in the Randomized Population | TVF | 88 participants |
| Coronary PCI Guided by OCT | The Results of Adjudicated Clinical Outcomes to 2 Years in the Randomized Population | TVF excluding PPMI | 74 participants |
| Coronary PCI Guided by Angiography | The Results of Adjudicated Clinical Outcomes to 2 Years in the Randomized Population | TLF | 86 participants |
| Coronary PCI Guided by Angiography | The Results of Adjudicated Clinical Outcomes to 2 Years in the Randomized Population | All Death, All MI, All Revascularization (DMR) | 187 participants |
| Coronary PCI Guided by Angiography | The Results of Adjudicated Clinical Outcomes to 2 Years in the Randomized Population | All Death | 44 participants |
| Coronary PCI Guided by Angiography | The Results of Adjudicated Clinical Outcomes to 2 Years in the Randomized Population | TVF excluding PPMI | 82 participants |
| Coronary PCI Guided by Angiography | The Results of Adjudicated Clinical Outcomes to 2 Years in the Randomized Population | All MI | 72 participants |
| Coronary PCI Guided by Angiography | The Results of Adjudicated Clinical Outcomes to 2 Years in the Randomized Population | TVF | 99 participants |
| Coronary PCI Guided by Angiography | The Results of Adjudicated Clinical Outcomes to 2 Years in the Randomized Population | All Revascularization | 120 participants |