• Scaffold retrieval methods (use of additional wires, snares, and / or forceps) may
result in additional trauma to the coronary vasculature and / or the vascular access
site. Complications may include bleeding, hematoma, or pseudoaneurysm.
• When multiple Absorb GT1 Bioresorbable Vascular Scaffolds and drug-eluting stents
are required, only Absorb GT1 Bioresorbable Vascular Scaffolds, Absorb Bioresorbable
Vascular Scaffolds or everolimus-eluting stents must be used. Potential interaction
with other drug-eluting stents or coated stents has not been evaluated and should
be avoided.
• The extent of the patient’s exposure to drug and polymer is directly related to the
number of scaffolds implanted. A patient can receive up to a total scaffolding length
of 94 mm.
• The safety and effectiveness of the Absorb GT1 BVS in patients with prior
brachytherapy of the target lesion or the use of brachytherapy for treated site
restenosis in an Absorb GT1 BVS have not been established. Both vascular
brachytherapy and the Absorb GT1 BVS alter arterial remodeling. The combination
between these two treatments has not been established.
•
Postdilatation with a noncompliant balloon is recommended
following instructions in
section
10.7 Further Expansion of the Deployed Scaffold,
as long as the postdilated
segment is within the allowable expansion limits of the scaffold.
• An unexpanded scaffold may be retracted into the guiding catheter
one time only.
An
unexpanded scaffold should not be reintroduced into the artery once it has been pulled
back into the guiding catheter. Subsequent movement in and out through the distal end
of the guiding catheter should not be performed, as the scaffold may be damaged or
dislodged during retraction back into the guiding catheter.
• Should resistance be felt at any time during removal of the undeployed Absorb GT1
BVS System, please refer to the steps provided in section
6.4 Scaffold / System
Removal – Precautions.
• In the rare event of acute occlusion following scaffold placement, a bailout implant
may be inserted and deployed within the scaffold such that the Absorb GT1 BVS is
completely covered by the bailout implant. All abrupt closures must be treated as an
emergency per the hospital standard of care.
Note:
It is recommended that bailouts be done with a metallic everolimus-eluting stent
of appropriate size.
6.3
Use in Conjunction with Other Procedures
• While vessel preparation in complex lesions may include the use of various mechanical
atherectomy devices, the safety and effectiveness have not been formally established
in clinical trials with use of either mechanical atherectomy devices (directional
atherectomy catheters, rotational atherectomy catheters) or laser angioplasty catheters
in conjunction with Absorb GT1 BVS implantation.
6.4
Scaffold / System Removal – Precautions
• Scaffold delivery system removal prior to scaffold deployment
If removal of a scaffold system is required prior to deployment, ensure that the guide
catheter is coaxially positioned relative to the scaffold delivery system and cautiously
withdraw the scaffold delivery system into the guiding catheter. Should
unusual
resistance
be felt
at any time
when withdrawing the scaffold into the guide catheter,
the scaffold delivery system and the guide catheter should be
removed as a single
unit.
This should be done under direct visualization with fluoroscopy.
• Withdrawal of the scaffold delivery system / postdilatation balloon from the deployed
scaffold
1. Deflate the balloon by pulling negative on the inflation device. Larger and longer
balloons will take more time (up to 30 seconds) to deflate than smaller and
shorter balloons. Confirm balloon deflation under fluoroscopy.
2. Position the inflation device to “negative” or “neutral” pressure.
3. Stabilize guide catheter position just outside coronary ostium and anchor in place.
Maintain guide wire placement across scaffold segment.
4. Gently remove the scaffold delivery system with slow and steady pressure.
5. Tighten the rotating hemostatic valve.
Notes:
1)
If, during withdrawal of the catheter from the deployed scaffold, resistance is
encountered, use the following steps to improve balloon rewrap:
°
Re-inflate the balloon up to nominal pressure, deflate and change pressure
to neutral.
°
Repeat steps 1 through 5 above.
2) After successful withdrawal of the balloon from the deployed scaffold, should
any resistance be felt
at any time
when withdrawing the scaffold delivery system
or postdilatation balloon into the guide catheter,
remove the entire system as a
single unit.
• Failure to follow these steps and / or applying excessive force to the delivery system
can potentially result in loss or damage to the scaffold and / or delivery system
components.
• If it is necessary to retain guide wire position for subsequent artery / lesion access,
leave the guide wire in place and remove all other system components.
6.5
Post Implant – Precautions
•
If necessary to cross a newly deployed scaffold
with a guide wire, balloon, delivery
system, or imaging catheters, exercise care to avoid disrupting the scaffold geometry.
• Antiplatelet therapy should be administered post-procedure (see section
9.1
Individualization of Treatment
).
6.6
MRI Statement
Comparison to the XIENCE PRIME metallic stents* indicates that the Absorb GT1 BVS is MR
Conditional and can be scanned safely under the following conditions:
• Static magnetic field of 3 Tesla or less
• Spatial gradient of 2500 Gauss/cm or less
• Maximum whole-body-averaged specific absorption rate (SAR) of 2.0 W/kg (normal
operating mode) for up to 15 minutes of scanning for each sequence
The Absorb GT1 BVS should not migrate in this MRI environment, nor should there be safety
concerns related to scaffold or marker heating. No concerns related to the effect of the
above MRI environment on the drug content or drug release rate are anticipated. Due to its
material properties, the same MR condition restrictions appropriate for the XIENCE PRIME
stent apply more conservatively to the Absorb GT1 BVS. It is unknown if MR image quality
will be compromised if the area of interest is in the exact same area or relatively close to the
position of the Absorb GT1 BVS.
*Nonclinical testing was completed on XIENCE PRIME units in single and in overlapped
configurations up to 71 mm in length and is on file with Abbott Vascular.
6.7
Drug Interactions
Everolimus is extensively metabolized by the cytochrome P4503A4 (CYP3A4) in the gut
wall and liver, and is a substrate for the countertransporter P-glycoprotein. Everolimus has
also been shown to reduce the clearance of some prescription medications when it was
administered orally along with cyclosporine (CsA). Hence, everolimus, when prescribed as
an oral medication, may interact with other medications that include (but are not restricted
to) inhibitors and inducers of CYP3A4 isozymes; absorption and subsequent elimination of
everolimus may be influenced by drugs that affect these pathways. Formal drug interaction
studies have not been performed with the Absorb GT1 BVS System. Therefore, due
consideration should be given to the potential for both systemic and local drug interactions in
the vessel wall, when deciding to place the Absorb GT1 BVS in a subject taking a drug with
known interaction with everolimus.
Everolimus, when prescribed as an oral medication, may interact with some drugs or
foods
1,2,3,4,5
including, but not limited to:
• CYP3A4 / PgP inhibitors that may increase everolimus blood concentrations:
°
Immunosuppressant cyclosporine
°
Antifungal agents (e.g., fluconazole, ketoconazole, itraconazole ketoconazole)
°
Macrolide antibiotics (e.g., clarithromycin, erythromycin)
°
Calcium channel blockers (e.g., verapamil, nicardipine, diltiazem)
°
Protease inhibitors (e.g., nelfinavir, indinavir, amprenavir)
°
Other substances (e.g., cisapride, metoclopramide, bromocriptine, cimetidine,
danazol)
• CYP3A4 inducers that may decrease everolimus drug concentrations:
°
Antibiotics (e.g., rifampin, rifabutin)
°
Anticonvulsants (e.g., carbamazepine, phenobarbital, phenytoin)
°
Non-nucleoside reverse transcriptase inhibitors (e.g., efavirenz, nevirapine)
°
Glucocorticoids (e.g., dexamethasone, prednisone, prednisolone)
°
HMGCoA reductase inhibitors (e.g., simvastatin, lovastatin)
°
Other (e.g., St. John’s Wort)
For more detailed drug interaction information, please reference the most recent everolimus
drug label
1, 2, 3 ,4, 5
.
6.8 Pregnancy
This product (the Absorb GT1 BVS System) and everolimus have not been tested in pregnant
or nursing women or in men intending to father children. Effects on the developing fetus have
not been studied. While there is no contraindication, the risks and reproductive effects are
unknown at this time.
7.0
ADVERSE EVENTS
7.1
Observed Adverse Events
Adverse events observed in the ABSORB clinical trials that are related to the key clinical
outcomes of death, cardiac death, myocardial infarction (MI)(Q-wave and non-Q-wave),
target lesion revascularization (TLR) (by percutaneous coronary intervention [PCI] or
coronary artery bypass graft), scaffold thrombosis, and ischemia-driven Major Adverse
Cardiac Event (MACE) (composite of cardiac death, MI, ischemia-driven TLR [ID-TLR]) are
presented in section
8.0 Clinical Investigations of Absorb BVS System.
All other adverse
events are included in section
7.2 Potential Adverse Events.
7.2
Potential Adverse Events
Adverse events that may be associated with PCI, treatment procedures, and the use of a
coronary scaffold in native coronary arteries include the following, but are not limited to:
• Abrupt closure
• Access site complications
• Allergic reaction or hypersensitivity
to contrast agent or polymer poly
(L-lactide) (PLLA), polymer poly (D,L-
lactide) (PDLLA), and drug reactions to
antiplatelet drugs or contrast agent
• Aneurysm
• Arrhythmias, including atrial and
ventricular
• Arterial perforation
• Arterial rupture
• Arteriovenous fistula
• Bleeding complications, which may
require transfusion
• Cardiac arrest
• Cardiac, pulmonary, or renal failure
• Cardiac tamponade
• Coronary artery spasm
• Coronary or scaffold embolism
• Coronary or scaffold thrombosis
• Death
• Dissection of the coronary artery
• Distal emboli (air, tissue, or thrombotic)
• Emergent or non-emergent surgery
• Fever
• Hypotension / hypertension
• Infection and pain
• Injury to the coronary artery
• Ischemia, myocardial
• Myocardial infarction
• Nausea and vomiting
• Palpitations
• Pericardial effusion
• Pericarditis
• Peripheral ischemia (due to vascular
injury)
• Peripheral nerve injury
• Pulmonary edema
• Pseudoaneurysm
• Renal insufficiency / failure
• Restenosis of scaffolded segment
• Shock
• Stroke / cerebrovascular accident
and TIA
• Total occlusion of coronary artery
• Unstable or stable angina pectoris
• Vascular complications, including entry
site, which may require vessel repair
• Ventricular arrhythmias, including
ventricular fibrillation and ventricular
tachycardia
• Vessel dissection
Adverse events associated with daily oral administration of everolimus in doses varying
from 1.5 mg to 10 mg daily can be found in the Summary of Product Characteristics (SPC)
and labels for the drug
1,2,3,4,5
. The risks described below include the anticipated adverse
events relevant for the cardiac population referenced in the contra-indications, warnings and
precaution sections of the everolimus labels / SPCs and/or observed at incidences ≥ 10% in
clinical trials with oral everolimus for different indications. Please refer to the drug SPCs and
labels
1,2,3,4,5
for more detailed information and less frequent adverse events.
• Abdominal pain
• Anemia
• Angioedema
• Arterial thrombotic events
• Bleeding and coagulopathy (including
Hemolytic uremic syndrome, thrombotic
thrombocytopenic purpura and
thrombotic microangiopathy)
• Constipation
• Cough
• Diabetes mellitus
• Diarrhea
• Dyspnea
• Embryo-fetal toxicity
• Headache
• Hepatic artery thrombosis
• Hepatic disorders (including hepatitis
and jaundice)
• Hypersensitivity to everolimus active
substance, to other rapamycin derivates
1
Certican
®
UK label Nov 2014
2
Afinitor
®
EU authorization SPC Dec 2014
3
Votubia
®
EU SPC Sept 2014
4
Afinitor
®
US label Dec 2014
5
Zortress
®
US label Feb 2013
Refer to www.MHRA.gov.uk, www.ema.europa.eu, and www.fda.gov for the most recent
versions of these SPC/labels.
• Hypertension
• Infection (bacterial, fungal, viral or
protozoan infections, including infections
with opportunistic pathogens. Polyoma
virus-associated nephropathy (PVAN),
JC virus associated progressive
multiple leukoencephalopathy (PML),
fatal infections and sepsis have been
reported in patients treated with oral
everolimus)
• Kidney arterial and venous thrombosis
• Laboratory test alterations
(elevations of serum creatinine,
proteinuria, hypokalemia;
hyperglycemia, dyslipidemia
including hypercholesterolemia and
hypertriglyceridemia; liver function tests
abnormal; decreases in hemoglobin,
lymphocytes, neutrophils, and platelets)
• Lymphoma and skin cancer
• Male infertility
• Nausea
• Nephrotoxicity (in combination with
cyclosporine)
• Non-infectious pneumonitis (including
interstitial lung disease)
• Oral ulcerations
• Pain
• Pancreatitis
• Pericardial effusion
• Peripheral oedema
• Pleural effusion
• Pneumonia
• Pyrexia
• Rash
• Renal failure
• Upper respiratory tract infection
• Urinary tract infection
• Venous thromboembolism
• Vomiting
• Wound healing complications (including
wound infections and lymphocele)
8.0
CLINICAL INVESTIGATIONS OF ABSORB BVS SySTEM
The Absorb GT1 BVS is based on the predicate device, Absorb BVS. The clinical
investigations outlined in section
8.0
were performed on the Absorb BVS.
The Absorb GT1 BVS has the same mode of expansion, backbone material, scaffold coating,
drug density, permanent scaffold markers, and scaffold design as the Absorb BVS. The
Absorb GT1 BVS differs from the Absorb BVS only in the scaffold delivery system. The
Absorb GT1 scaffold delivery system utilizes the same principle of operation and materials as
other Abbott Vascular RX stent / scaffold systems and coronary dilatation catheters.
Based on the identical nature of the Absorb GT1 scaffold to the Absorb scaffold,
performance of the Absorb GT1 BVS can be predicted to be similar to the performance of
Absorb BVS. Therefore, clinical trial data for Absorb BVS are summarized in this section.
8.1
ABSORB Clinical Trial
The ABSORB clinical investigation is a prospective, single-arm, open-label, multicenter,
international clinical study to evaluate safety and performance of the Absorb BVS in coronary
arteries. The study was designed to enroll up to 30 patients (Cohort A) at 4 clinical sites
followed by approximately 101 patients (Cohort B) at 12 clinical sites in Europe and Asia
Pacific region.
Eligible Criteria:
Patients at least 18 years of age with evidence of angina, myocardial
ischemia, or a positive functional test; female patients with childbearing potential with
a negative pregnancy test within 7 days prior to the index procedure and effective
contraception during participation in this clinical investigation; and patients who signed
an informed consent prior to enrollment. Angiographic inclusion criteria included: Nominal
vessel diameter of 3.0 mm; lesion length ≤ 8 mm by visual estimation extended to ≤ 14 mm
for the 3.0 x 18 mm scaffold; % diameter stenosis (%DS) of ≥ 50% and < 100%; TIMI flow
of ≥ 1. Key angiographic exclusion criteria included: aorto-ostial location; left main location
within 2 mm of the origin of the LAD or LCX; excessive tortuosity proximal to or within the
lesion; extreme angulation (≥ 90°); heavy calcification; restenotic from previous intervention;
target vessel containing thrombus; other clinically significant lesions in the target vessel or
side branch.
Treatment Strategy:
Predilatation of the target lesion was mandatory. Planned overlapping
of Absorb BVS was disallowed. Any bailout must be done with overlapping a XIENCE V stent
of appropriate length, and if not available, a CYPHER
®
sirolimus-eluting stent; bailout with
Absorb BVS was not permitted. Postdilatation was performed at operator discretion, but only
using balloons sized to fit within the boundaries of the scaffold.
Antiplatelet Regimen:
Subjects not on chronic antiplatelet medications had to receive a
loading dose of clopidogrel bisulfate ≥ 300 mg and aspirin ≥ 300 mg 6 to 72 hours prior to
the index procedure if possible, but no later than 1 hour after the procedure. All patients were
required to receive anticoagulation and other therapy during scaffold implantation according
to the standard of care at the clinical site. All patients were to be maintained on 75 mg
clopidogrel bisulfate daily for a minimum of 6 months and ≥ 75 mg of aspirin daily for the
length of the clinical investigation (5 years). Patients who developed sensitivity to clopidogrel
bisulfate were to be switched to ticlopidine hydrochloride at a dose in accordance with
standard hospital practice.
8.2
ABSORB Cohort A
8.2.1 Methodology and Current Status
A total of 30 patients in Cohort A were enrolled between March 7, 2006 and July 18, 2006 at
four clinical sites in Europe and New Zealand.
The ABSORB Cohort A Trial implanted the Absorb Cohort A BVS in patients with a single
de novo
native coronary artery lesion. Enrollment started with the 3.0 x 12 mm size. The
3.0 x 18 mm size became available later during enrollment and was used in only two
patients.
Clinical follow-up through 30 days, 180 days, 270 days, 1 year, 18 months, 2 years, 3 years,
4 years, and 5 years, and angiographic, IVUS, IVUS-VH, palpography, OCT data at 180 days
and 2 years are available. MSCT data at 18 months and coronary vasomotor test data at
2 years are also available. No further clinical observations will be performed for ABSORB
Cohort A since 5-year follow-up was the last visit time point.
8.2.2 Clinical Outcome at 5 Years
At 5 years, the ischemia-driven MACE (defined as the composite endpoint of cardiac death,
MI or ID-TLR) rate was 3.4% (
Table 4
). There was only one non-Q-wave MI (peak troponin
2.21 μg/L) related to the treatment of a non-flow-limiting stenosis (QCA diameter stenosis
42%) of an Absorb BVS implanted 46 days earlier, in a patient who had one episode of
angina at rest without electrographic evidence of ischemia. For a perceived safety reason,
the polymeric scaffold was covered by a drug-eluting metallic stent. No new MACE was
recorded between 6 months and 5 years. No instances of scaffold thrombosis arose
according to the protocol or the Academic Research Consortium (ARC) definitions.
Table 4: Clinical Outcome at 5 years
Hierarchical
Rates
6 Months
(N = 30)
12 Months
(N = 29)
†
2 years
(N = 29)
†
3 years
(N = 29)
†
4 years
(N = 29)
†
5 years
(N = 29)
†
Cardiac
Death, %
0
0
0
0
0
0
MI, % (n)
3.3 (1)*
3.4 (1)*
3.4 (1)*
3.4 (1)*
3.4 (1)*
3.4 (1)*
Q-Wave MI
0
0
0
0
0
0
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