Clinical trial NCT01308346: ABSORB PHYSIOLOGY Clinical Investigation
Official title: ABSORB PHYSIOLOGY Clinical Investigation: Clinical Evaluation of the Short and Long-Term Effects of the Abbott Vascular Everolimus-Eluting Bioresorbable Vascular Scaffold on Coronary Artery Blood Flow and Physiological Responsiveness
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Coronary Artery Disease
Keywords: Bioabsorbable
Coronary Stent
Everolimus
drug eluting stents
stents
angioplasty
coronary artery disease
total coronary occlusion
coronary artery restenosis
stent thrombosis
myocardial ischemia
coronary artery stenosis
Lead sponsor: Abbott Medical Devices
Sponsor class: INDUSTRY
First posted: 2011-03-04
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL

Brief summary: The target enrollment goal for the trial was to enroll 36 subjects. However due to a challenging protocol inclusion/ exclusion criteria, only one subject was enrolled since the trial was initiated in June 2011.

To evaluate the following in participants undergoing coronary artery scaffolding/stenting for significant coronary artery disease:

* The acute (post-implantation) effect of an implanted bioresorbable vascular scaffold (BVS) or metallic drug eluting stent (mDES) on coronary blood flow and physiological responsiveness of the target coronary artery
* The long-term (2 years) effect of an implanted BVS or mDES on coronary blood flow and physiological responsiveness of the target coronary artery

Detailed description: * Prospective, randomized, single-blinded, multi-center clinical investigation comparing target vessel and non-intervened, self-control vessel within participants and between participants undergoing BVS or mDES deployment for the treatment of a single de novo native coronary artery lesion
* The investigation will include two arms:

  * Study device (BVS) arm: Abbott Vascular's Everolimus-Eluting Bioresorbable Vascular Scaffold
  * Control device (mDES) arm: Abbott Vascular's Everolimus-Eluting XIENCE V or XIENCE PRIME

Eligibility criteria: Inclusion Criteria:

1. Participant must be a male of at least 18 years of age or a female that is post-menopausal and not on hormone replacement therapy.
2. Participant is able to verbally confirm understanding of risks, benefits and treatment alternatives and he/she or his/her legally authorized representative must provide written informed consent prior to any clinical investigation related procedure, as approved by the appropriate Ethics Committee of the respective clinical site.
3. Participant must have evidence of myocardial ischemia (e.g., stable or unstable angina, silent ischemia with a positive functional study).
4. Participant must be an acceptable candidate for coronary artery bypass graft (CABG) surgery.
5. Participant must agree to undergo all clinical investigation plan-required follow-up visits.
6. Participant must agree not to participate in any other clinical investigation for a period of 2 years following the index procedure. This includes clinical trials of medications and invasive procedures. Only questionnaire-based studies are allowed.

Angiographic Inclusion Criteria:

1. A single de novo native coronary artery lesion suitable to be treated by either a BVS or a mDES.
2. Target lesion must be located in a native coronary artery in which the mean proximal and distal vessel diameter of the target lesion (Dmean) fall within the range of ≥ 2.25 mm and ≤ 3.25 mm and the target lesion length measures ≤ 22 mm as assessed by IVUS.
3. Target lesion must be located in the main branch of a major epicardial vessel (i.e., LAD, LCX, or RCA) with a visually estimated diameter stenosis of ≥ 50% and \< 100% with a TIMI flow of ≥ 1.
4. Participant must have an additional angiographically smooth (\< 40% diameter stenosis) non-target vessel to act as an intra-participant control vessel (self-control vessel). The self-control vessel must be the main branch of a major epicardial vessel (i.e., LAD, LCX, or RCA).
5. Coronary anatomy must be suitable for IVUS, OCT, and pressure and flow wire instrumentation.

General Exclusion Criteria:

1. Participant has a known diagnosis of spontaneous acute myocardial infarction (AMI) within 14 days preceding the index procedure.
2. Participant has high-risk acute coronary syndrome (e.g., dynamic ST-T wave change on ECG or recurrent chest pain/nitrate-unresponsive prolonged chest pain at rest within 48 hours prior to the index procedure).
3. Participant has any evidence of myocardial infarct in the territory subtended by the proposed target vessel or self-control vessel.
4. Participant has current unstable arrhythmias.
5. Participant has chronic atrial fibrillation.
6. Participant has a known left ventricular ejection fraction (LVEF) \< 40%.
7. Participant has received a heart transplant or any other organ transplant or is on a waiting list for any organ transplant.
8. Participant has previously had CABG or mitral or aortic valve repair/replacement.
9. Participant is receiving or scheduled to receive chemotherapy for malignancy within 30 days prior to or after the index procedure.
10. Participant is receiving immunosuppressant therapy or has known immunosuppressive or autoimmune disease (e.g., human immunodeficiency virus, systemic lupus erythematosus, etc.).
11. Participant has a chronic systemic condition or medication likely to interfere with coronary physiology and/or conduit artery function (e.g., chronic inflammatory condition, chronic renal failure, or chronic obstructive pulmonary disease).
12. Participant has known renal insufficiency.
13. Participant is receiving or scheduled to receive any planned radiotherapy.
14. Participant is receiving chronic anticoagulation therapy (e.g., heparin, coumadin) at the onset of the clinical investigation.
15. Participant has a known hypersensitivity or contraindication to aspirin, heparin/bivalirudin, anti-platelet medications specified for use in the study (clopidogrel, prasugrel and ticlopidine, inclusive), everolimus, poly (L-lactide), poly (DL-lactide), cobalt, chromium, nickel, platinum, tungsten, acrylic and fluoro polymers, or contrast sensitivity that cannot be adequately pre-medicated.
16. Elective surgery is planned within the first 6 months after the index procedure that will require discontinuing aspirin, clopidogrel, prasugrel, or ticlopidine.
17. Participant has a platelet count \< 100,000 cells/mm3 or \> 700,000 cells/mm3, a WBC of \< 3,000 cells/mm3, or documented or suspected liver disease (including laboratory evidence of hepatitis) within 7 days prior to the index procedure.
18. Participant has a history of bleeding diathesis or coagulopathy or will refuse blood transfusions.
19. Participant has had a cerebrovascular accident/stroke (CVA) or transient ischemic neurological attack (TIA) within the past 6 months.
20. Participant has had a significant gastro-intestinal or significant urinary bleed within the past 6 months.
21. Participant has extensive peripheral vascular disease that precludes safe 6 French sheath insertion.
22. Participant has a history of paradoxical exercise-induced vasoconstriction that is consistent with myocardial bridging in the coronary anatomy.
23. Participant has other medical illness (e.g., cancer or congestive heart failure) or known history of substance abuse (alcohol, cocaine, heroin etc.) that in the judgment of the Investigator may cause non-compliance with the clinical investigation plan, confound the data interpretation or is associated with a limited life expectancy.
24. Participant is currently participating in another clinical investigation that has not yet reached its primary endpoint.
25. Percutaneous interventions for lesions in the third major epicardial vessel (the one that does not contain the target or the self-control vessel) were performed within 30 days preceding the index procedure or are planned to be done within 6 months following the index procedure.
26. Planned PCI procedures in the target vessel (and/or any of its side branches) or the self-control vessel (and/or any of its side branches) within 2 years following the index procedure.
27. Participant who does not suspend drugs that will influence vaso-function.

Angiographic Exclusion Criteria

1. Target lesion meets any of the following criteria:

   1. Left main location;
   2. RCA aorto-ostial location (within 10 mm from expected proximal stent/scaffold edge);
   3. LAD or LCX ostial location (within 10 mm from expected proximal stent/scaffold edge);
   4. Involves a bifurcation with a side branch ≥ 2 mm in diameter, an ostial lesion \> 40% stenosed by visual estimation, or a side branch requiring pre-dilatation;
   5. Total occlusion (TIMI flow 0) prior to wire crossing;
   6. Excessive tortuosity proximal to or within the lesion;
   7. Extreme angulation (≥ 90°) proximal to or within the lesion;
   8. Heavy calcification in the lesion;
   9. Located in a side branch.
2. Participant has a high probability that a procedure other than pre-dilatation, scaffold/stent implantation, and post-dilatation (if applicable) will be required at the time of index procedure for treatment of the target vessel (e.g., atherectomy, cutting balloon or brachytherapy).
3. The target vessel (and/or any of its side branches) or the self-control vessel (and/or any of its side branches) contains visible thrombus.
4. The target vessel or the self-control vessel has previously been treated by any PCI procedures.
5. A side branch of the target vessel or a side branch of the self-control vessel has received any percutaneous interventions within 30 days prior to the index procedure.
6. Another clinically significant lesion is located in the target vessel (and/or any of its side branches) or the self-control vessel (and/or any of its side branches) that may require PCI treatments within 2 years following the index procedure.
7. Participant has evidence of myocardial bridging in the coronary anatomy during the angiographic evaluation.

Primary outcomes:
measure: Coronary artery endothelial responsiveness
timeFrame: Post procedure
Secondary outcomes:
measure: Coronary artery cross-sectional compliance and cross-sectional distensibility
timeFrame: Post procedure
measure: Target artery endothelial shear stress distribution
timeFrame: Post procedure
measure: Wave intensity patterns in the coronary arteries
timeFrame: Post procedure
measure: Systolic and diastolic coronary artery impedance
timeFrame: Post procedure
measure: Clinical device success
timeFrame: Post procedure
measure: Clinical Procedure Success
timeFrame: during the hospital stay with a maximum of 7 days post index procedure.
measure: Cardiac Death (CD)
timeFrame: 180 days
measure: Cardiac Death (CD)
timeFrame: 1 year
measure: Cardiac Death (CD)
timeFrame: 2 years
measure: Myocardial Infarction (MI)
timeFrame: 180 days
measure: Myocardial Infarction (MI)
timeFrame: 1 year
measure: Myocardial Infarction (MI)
timeFrame: 2 years
measure: Target Vessel Myocardial Infarction (TV-MI)
timeFrame: 180 days
measure: Target Vessel Myocardial Infarction (TV-MI)
timeFrame: 1 year
measure: Target Vessel Myocardial Infarction (TV-MI)
timeFrame: 2 years
measure: All Death, All MI, All Revascularization (DMR)
timeFrame: 180 days
measure: All Death, All MI, All Revascularization (DMR)
timeFrame: 1 year
measure: All Death, All MI, All Revascularization (DMR)
timeFrame: 2 years
measure: Ischemia-Driven MACE (ID-MACE)
timeFrame: 180 days
measure: Ischemia-Driven MACE (ID-MACE)
timeFrame: 1 year
measure: Ischemia-Driven MACE (ID-MACE)
timeFrame: 2 years
measure: Ischemia-Driven Target Vessel Failure (ID-TVF)
timeFrame: 180 days
measure: Ischemia-Driven Target Vessel Failure (ID-TVF)
timeFrame: 1 year
measure: Ischemia-Driven Target Vessel Failure (ID-TVF)
timeFrame: 2 years
measure: Ischemia-Driven Target Vessel Revascularization (ID-TVR)
timeFrame: 180 days
measure: Ischemia-Driven Target Vessel Revascularization (ID-TVR)
timeFrame: 1 year
measure: Ischemia-Driven Target Vessel Revascularization (ID-TVR)
timeFrame: 2 years
measure: Ischemia-Driven Self-Control Vessel Revascularization (ID-SCVR)
timeFrame: 180 days
measure: Ischemia-Driven Self-Control Vessel Revascularization (ID-SCVR)
timeFrame: 1 year
measure: Ischemia-Driven Self-Control Vessel Revascularization (ID-SCVR)
timeFrame: 2 years
measure: Ischemia-Driven Non-Target, Non-Self-Control Vessel Revascularization (ID-NTNSCVR)
timeFrame: 180 days
measure: Ischemia-Driven Non-Target, Non-Self-Control Vessel Revascularization (ID-NTNSCVR)
timeFrame: 1 year
measure: Ischemia-Driven Non-Target, Non-Self-Control Vessel Revascularization (ID-NTNSCVR)
timeFrame: 2 years
measure: Ischemia-Driven Target Lesion Revascularization (ID-TLR)
timeFrame: 180 days
measure: Ischemia-Driven Target Lesion Revascularization (ID-TLR)
timeFrame: 1 year
measure: Ischemia-Driven Target Lesion Revascularization (ID-TLR)
timeFrame: 2 years
measure: Scaffold/Stent thrombosis
timeFrame: 180 days
measure: Scaffold/Stent thrombosis
timeFrame: 1 year
measure: Scaffold/Stent thrombosis
timeFrame: 2 years
measure: Coronary artery endothelial responsiveness
timeFrame: 2 years
measure: Coronary artery cross-sectional compliance and cross-sectional distensibility
timeFrame: 2 years
measure: Target artery endothelial shear stress distribution
timeFrame: 2 years
measure: Wave intensity patterns in the coronary arteries
timeFrame: 2 years
measure: Systolic and diastolic coronary artery impedance
timeFrame: 2 years
Other outcomes:
Locations:
city: Heidelberg
country: Australia
facility: Austin Health
state: Victoria
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
city: Melbourne
country: Australia
facility: Monash Medical Centre
city: Hong Kong
country: China
facility: Queen Elizabeth
city: Rotterdam
country: Netherlands
facility: Maasstad Ziekenhuis
city: Singapore
country: Singapore
facility: National Heart Centre Singapore
Study officials:
affiliation: Monash Medical Center
name: Ian Meredith, Prof, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Monash Medical Center
name: James Cameron, Prof, MD
role: PRINCIPAL_INVESTIGATOR
References: