Spectranetics AngioSculpt X Mode D'emploi page 5

• Appropriate dual antiplatelet, anticoagulant and coronary
vasodilator therapy should be administered before, during, and after
treament with the AngioSculpt®X catheter. Antiplatelet therapy for
less than 3 months following treatment with the AngioSculpt®X
catheter has not been studied and patients in the rst-in-human
study were administered dual antiplatelet therapy consisting of
aspirin plus either clopidogrel or ticlopidine for a minimum of
3 months following treatment with the AngioSculpt®X catheter.
• Do not rotate the catheter shaft in excess of 180 degrees when the
tip is constrained.
• Do not rotate the catheter luer hub in excess of ve (5) turns
during use.
• Do not advance or retract the AngioSculpt®X catheter over the
oppy portion of the guide wire.
• Catheter manipulation, including advancement and retraction,
should be performed by grasping the hypotube shaft.
• If unusual resistance is felt when the catheter is being manipulated
or if it is suspected that the guide wire has become kinked, carefully
remove the entire catheter system (AngioSculpt®X catheter and
steerable guide wire) as a unit.
• If uoroscopic guidance indicates that the AngioSculpt®X catheter
has advanced beyond the end of the guide wire, withdraw the
catheter and reload the wire before advancing again.
• It is not recommended that the AngioSculpt®X catheter be used in
conjunction with other drug coated balloons or drug eluting stents
to treat the same lesion in the same procedure or within 90 days.
The safety of combinations of di erent drug-device products has
not been assessed.
• DO NOT resterilize or reuse this device, as these actions can
compromise device performance or increase the risk of cross-
contamination due to inappropriate reprocessing.
• Reuse of this single use device could lead to serious patient injury
or death and voids manufacturer warranties.
VI. DRUG INFORMATION
Mechanism of Action
The AngioSculpt®X Drug-Coated PTCA Scoring Balloon Catheter coating
contains paclitaxel, an anti-proliferative pharmaceutical agent that
speci cally binds to and stabilizes microtubules. By blocking microtubule
depolymerization, paclitaxel a ects inhibition of smooth muscle cell and
broblast proliferation and migration as well as secretion of extracellular
matrix. The combination of these e ects results in the inhibition of
neointimal hyperplasia and therefore prevents restenosis.
Pharmacokinetics
The maximum paclitaxel plasma level measured after 10 minutes
in the porcine model was 4.6 ng/mL, signi cantly lower than the
myelosuppression level of ≥85 ng/mL. After 24 hours, the paclitaxel
plasma level dropped to less than 0.4 ng/mL. The excipient NDGA could
not be detected in plasma (LOQ: 2 ng/mL). The observed peak levels
and total serum exposure of the AngioSculpt®X catheter are therefore
roughly 50 to 200-fold lower than that reported for pharmaceutical
paclitaxel (3 h. infusion, Taxol™ package insert: T1/2 = 12.1 to 20.2 hours,
Cmax = 2170 to 3650 ng/mL, and AUC = 7952 to 15007 ng*h/mL).
After 10 minutes, paclitaxel tissue levels at the target lesion reached 7.1%
of the nominal drug dose, or 142 ng/mg. Between 1 and 28 days, the tissue
level stabilized at 1.1% of the nominal drug dose, or 15 ng/mg. The mean
concentration of paclitaxel in coronary arteries was approximately 10 µM
which is within the range of paclitaxel concentrations (0.1 to 10 µM/L)
known to inhibit the proliferation of human arterial smooth muscle
cells (Axel et al., 1997). The excipient NDGA could not be detected in the
artery wall.
Drug Interactions
No peer-reviewed drug interaction studies have evaluated the
AngioSculpt®X catheter. Therefore, the instructions for use of all
concurrent drug therapies should be consulted for interactions with
paclitaxel. When using the AngioSculpt®X catheter on a patient who is
taking a drug with known paclitaxel interactions or when initiating a
drug therapy in a patient who has recently undergone treatment with
the AngioSculpt®X catheter, the potential for both local and systemic
drug interactions should be considered. Paclitaxel is metabolized by
cytochrome P450 isoenzymes CYP2C8 and CYP3A4, and is a substrate of
P-glycoprotein. Agents that compete with or inhibit these isoenzymes
P009923-D 22NOV19 (2019-11-22)
may lead to increased levels of paclitaxel. Caution should be exercised
when administering paclitaxel with known substrates or inhibitors of the
cytochrome P450 isoenzymes CYP2C8 and CYP3A4, especially when no
reliable clinical data exists to describe the e ects of the drug interactions.
Carcinogenicity, Genotoxicity, and Reproductive Toxicology
No long-term animal studies have been published in which the
carcinogenic potential of paclitaxel was assessed. Similarly, there are
no adequate and well-controlled studies on the e ects of paclitaxel in
pregnant women or in men intending to father children. Paclitaxel's
mechanism of action involves interfering with cell proliferation through
microtubule stabilization, which may result in the loss of chromosomes
during cell division. Although paclitaxel was not mutagenic in the Ames
test or in the CHO/HGPRT and salmonella assays, this indirect action
has been shown to cause DNA fragmentation within in vitro and in vivo
micronucleus genotoxicity assays. Paclitaxel has also been reported to
cause chromosomal aberrations in primary human lymphocytes.
The treating physician should weigh the potential medical bene ts
of the AngioSculpt®X catheter against these potential genotoxic and
reproductive risks.
VII. ADVERSE EFFECTS
Possible adverse e ects include, but are not limited to, the following:
• Death
• He art Attack (acute
myocardial infarction)
• Total occlusion of the treated
coronary artery
• Coronary artery dissection,
perforation, rupture, or injury
• Pericardial tamponade
• No/slow re ow of
treated vessel
• Emergency coronary artery
bypass (CABG)
• Emergency percutaneous
coronary intervention
• CVA/stroke
• Pseudoaneurysm
• Restenosis of the
dilated vessel
• Unstable angina
• Thromboembolism or
retained device components
There may be other potential adverse events that are unforeseen at
this time.
VIII. SUMMARY OF CLINICAL STUDY
Multi-Center First-In-Human Clinical Trial
STUDY DESIGN
PATENT-C was a rst-in-human, multi-center, controlled, randomized,
single-blind, prospective clinical investigation comparing novel
paclitaxel-coated AngioSculpt scoring balloon with otherwise identical
commercially available bare AngioSculpt balloons in patients with
signi cant (≥70%) coronary artery bare metal in-stent restenosis.
The study evaluated the e cacy, safety and acute tolerance of
paclitaxel-coated AngioSculpt balloons in inhibiting bare metal stent
(BMS) restenosis.
A total of 61 patients were enrolled at ve clinical sites: 4 sites in
Germany and 1 site in Brazil. Thirty-three patients were randomized
to paclitaxel-coated balloon and 28 patients were randomized to the
bare control group. Protocol required follow-up included quantitative
coronary angiography (QCA) performed at 6 months following the index
procedure and clinical follow-up at 30 days and 6, 12, and 24 months
after the index procedure.
A blinded, independent core lab performed QCA analysis of all the lms
for the interventional procedure, all 6 month follow-up angiographies,
target lesion revascularization up to 6 month follow-up, and other
unscheduled angiographies or reinterventions up to 6 months.
Additionally, a blinded, independent Clinical Events Committee (CEC)
adjudicated all deaths; myocardial infarctions; target lesion and target
vessel revascularizations; and device failures.
• Irregular heart rhythm
(arrhythmias, including
life-threatening
ventricular arrhythmias)
• Severe low (hypotension)/
high (hypertension)
blood pressure
• Coronary artery spasm
• Hemorrhage or hematoma
• Need for blood transfusion
• Surgical repair of vascular
access site
• Creation of a pathway for
blood ow between the
artery and the vein in the
groin (arteriovenous stula)
• Drug reactions, allergic
reactions to x-ray dye
(contrast medium)
• Infection
• Allergic reaction to the
drug coating drug coating
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