1 1
PUFs
PUFs
Trial
Trial
Overview
Overview
™
™
(Pipeline
(Pipeline
Embolization
Embolization
Device
Device
for for
Uncoilable
Uncoilable
or Failed
or Failed
Aneurysms)
Aneurysms)
TheThe
multi-center,
multi-center,
prospective
prospective
clinical
clinical
trialtrial
thatthat
led led
to the
to the
pre-market
pre-market
approval
approval
(PMA)
(PMA)
of the
of the
Pipeline
Pipeline
embolization
embolization
device.
device.
Pipeline
Pipeline
Embolization
Embolization
Device
Device
™
™
Pipeline
Pipeline
Embolization
Embolization
Device
Device
forfor
Uncoilable
Uncoilable
or Failed
or Failed
Aneurysms
Aneurysms
(PUFs):
(PUFs):
Results
Results
of aofMulticenter
a Multicenter
Clinical
Clinical
Trial
Trial
TiborTibor
Becske,
Becske,
David
David
Kallmes,
Kallmes,
Isil Saatci,
Isil Saatci,
Cameron
Cameron
McDougall,
McDougall,
Istvan
Istvan
Szikora,
Szikora,
Giuseppe
Giuseppe
Lanzino,
Lanzino,
Christopher
Christopher
Moran,
Moran,
Henry
Henry
Woo,Woo,
Demetrius
Demetrius
Lopes,
Lopes,
Aaron
Aaron
Berez,
Berez,
Daniel
Daniel
Cher,Cher,
Adnan
Adnan
Siddiqui,
Siddiqui,
EladElad
Levy,Levy,
Felipe
Felipe
Albuquerque,
Albuquerque,
David
David
Fiorella,
Fiorella,
ZsoltZsolt
Berentei,
Berentei,
Saruhan
Saruhan
Cekirge
Cekirge
and and
PeterPeter
Kim Kim
Nelson
Nelson
STUDY
STUDY
DESIGN
DESIGN
DualDual
Anti-Platelet
Anti-Platelet
Protocol
Protocol
t
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t
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A
t t*ODMVTJPO$SJUFSJB
*ODMVTJPO$SJUFSJB
A
o-BSHFHJBOUTJ[FȴNN
BOEXJEFOFDLFEȴNN
o-BSHFHJBOUTJ[FȴNN
BOEXJEFOFDLFEȴNN
o4BDDVMBSPSGVTJGPSN
o4BDDVMBSPSGVTJGPSN
o1FUSPVTUPTVQFSJPSIZQPQIZTFBM*$"
o1FUSPVTUPTVQFSJPSIZQPQIZTFBM*$"
t t4BGFUZBOEFďDBDZPVUDPNFTXFSFDPNQBSFEUPBIJTUPSJDBMDPOUSPMXIJDI
4BGFUZBOEFďDBDZPVUDPNFTXFSFDPNQBSFEUPBIJTUPSJDBMDPOUSPMXIJDI
XBTCBTFEPOBOFYUFOTJWFMJUFSBUVSFSFWJFXPGUIFOBUVSBMIJTUPSZBOE
XBTCBTFEPOBOFYUFOTJWFMJUFSBUVSFSFWJFXPGUIFOBUVSBMIJTUPSZBOE
PVUDPNFTGPSUSBEJUJPOBMUSFBUNFOUTGPSUIJTQPQVMBUJPOPGBOFVSZTNT
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t
t"OHJPHSBQIJDPVUDPNFTJOUFSQSFUFECZBOJOEFQFOEFOUDPSFMBC
"OHJPHSBQIJDPVUDPNFTJOUFSQSFUFECZBOJOEFQFOEFOUDPSFMBC
PRE TREATMENT
PRE TREATMENT
- Aspirin
- Aspirin
325 mg
325orally
mg orally
daily for
daily2 for
days2 days
prior and
priorclopidogrel
and clopidogrel
75 mg75daily
mg for
daily for
7 days7 prior
days to
prior
treatment
to treatment
OR OR
- 600
- mg
600loading
mg loading
dose dose
of clopidogrel
of clopidogrel
1 day1prior
day to
prior
treatment
to treatment
POSTPOST
TREATMENT
TREATMENT
- Aspirin
- Aspirin
325 mg
325daily
mg for
dailyatfor
least
at least
6 months
6 months
post treatment
post treatment
- Clopidogrel
- Clopidogrel
75 mg75daily
mg for
dailyatfor
least
at least
3 months
3 months
post treatment
post treatment
- Most
- Most
were were
maintained
maintained
on combination
on combination
therapy
therapy
for 6 for
months
6 months
ANEURYSM
ANEURYSM
CHARACTERISTICS
CHARACTERISTICS
MeanMean
Size Size Range
Range
(mm)(mm)
(mm)(mm)
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16'TXBTDPNQSJTFEPGDIBMMFOHJOHBOFVSZTNTUIBUBSFEJďDVMUUPUSFBU
2,3
2,3
TVDDFTTGVMMZXJUIUSBEJUJPOBMUSFBUNFOUT
TVDDFTTGVMMZXJUIUSBEJUJPOBMUSFBUNFOUT
20%20%
giant
giant 80%80%
largelarge
(≥ 25(≥mm)
25 mm)(10 -(10
< 25
- <mm)
25 mm)
B
Aneurysm
Aneurysm 18.2 18.2 6.2B –6.2
36.1
– 36.1
NeckNeck
4.1 –4.1
36.1
– 36.1
Aneurysm
Aneurysm
Location
Location
#
#
%
Intra-Dural:
Intra-Dural:
(Paraopthalmic,
(Paraopthalmic,
Superior
Superior
Hypophyseal,
Hypophyseal,
Supraclinoid,
Supraclinoid,
Carotid
Carotid
Cave,Cave,
Lateral
Lateral
Clinoidal)
Clinoidal)
58
58
54% 54%
Extra-Dural:
Extra-Dural:
(Cavernous,
(Cavernous,
Petrous)
Petrous)
49
49
45% 45%
1
1
1% 1%
C
C
Off-Target
Off-Target
Location:
Location:
(Posterior
(Posterior
Communicating)
Communicating)
TOTALTOTAL
A. See A.
publication
See publication
for complete
for complete
list of alllist
inclusion
of all inclusion
and exclusion
and exclusion
criteria. criteria.
8.8 8.8
B. OneB.6.2One
mm 6.2
aneurysm
mm aneurysm
was treated
was but
treated
excluded
but excluded
from efficacy
from efficacy
analysisanalysis
108 108
%
100%100%
C. Excluded
C. Excluded
from efficacy
from efficacy
analysisanalysis
Pipeline Embolization Device
™
EFFICACY, TECHNICAL SUCCESS & FOLLOW-UP OUTCOMES:
The PUFs trial proved the effectiveness of the Pipeline device by achieving a 73.6%
rate of complete aneurysm occlusion at 180 days (without >50% stenosis or alternative
treatment), which was significantly higher than the pre-set target of >50%.
PRIMARY EFFICACY ENDPOINT
SECONDARY EFFICACY ENDPOINT
% of Aneurysms with Complete Occlusion without
>50% Stenosis or Alternative Treatment
% of Aneurysms with Complete Occlusion
73.6% = 78/106
75
50
D
PRE-SET TARGET RATE
50
25
180 days
0
DEFINITION
3BUFPGDPNQMFUFBOFVSZTNPDDMVTJPOBUEBZTXJUI
PVUNBKPS
TUFOPTJTPSVTFPGBMUFSOBUJWFUSFBUNFOU
180 days
0
CBTFEPOFYUFOTJWFSFWJFXPGPVUDPNFTJO
DMJOJDBMMJUFSBUVSF
RIGOROUS SUCCESS CRITERIA
t
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BEKVEJDBUFE
UPCFDPOTJEFSFEBTVDDFTT
t
"OFVSZTNTXJUIPVUEBZBOHJPHSBNTXFSF
DPOTJEFSFEGBJMVSFT
1 year
TECHNICAL SUCCESS RATE
—
TARGET RATE
t
85.7% = 78/91
F
E
75
25
t
81.8% = 81/99
Pipeline device placement was technically
successful in 107 of 108 cases (99%)
FOLLOW-UP RATES
—
At 180 days, PUFs had a 96.2% rate of follow-up
D. The study enrolled 110 aneurysms. 4 were excluded because of wrong location/size or
access not obtained. 106 aneurysms were included in the primary efficacy endpoint analysis.
E. 7 patients without 6-month angiographic follow-up were excluded from this analysis.
F. 8 additional patients did not have 1-year angiographic follow-up were excluded from this analysis.
SAFETY
SAFETY
OUTCOMES:
OUTCOMES:
™
™
TheThe
PUFs
PUFs
trialtrial
proved
proved
the the
safety
safety
of the
of the
Pipeline
Pipeline
device
device
withwith
a 5.6%
a 5.6%
raterate
of major
of major
ipsilateral
ipsilateral
stroke
stroke
or neurologic
or neurologic
death
death
at 180
at 180
daysdays
(without
(without
alternative
alternative
treatment),
treatment),
which
which
waswas
significantly
significantly
lower
lower
thanthan
the the
pre-set
pre-set
target
target
of <20%.
of <20%.
PRIMARY
PRIMARY
SAFETY
SAFETY
ENDPOINT
ENDPOINT
CONCLUSIONS
CONCLUSIONS
% of%Patients
of Patients
withwith
Major
Major
Stroke
Stroke
or or
Neurologic
Neurologic
Death
Death
at 180
at 180
DaysDays
25 25
20 20
PRE-SET
PRE-SET
TARGET
TARGET
RATERATE
15 15
10 10
5 5
0 0
5.6%
5.6%
= 6/107
= 6/107
G
G
180180
daysdays
DEFINITION
DEFINITION
— —PUFs
PUFs
included
included
a cohort
a cohort
of challenging
of challenging
to treat
to treat
aneurysms
aneurysms
including
including
giant
giant
andand
fusiform
fusiform
aneurysms
aneurysms
(18.2
(18.2
mmmm
average
average
size)
size)
t t3BUFPGNBKPSJQTJMBUFSBMTUSPLFPSOFVSPMPHJDEFBUI
3BUFPGNBKPSJQTJMBUFSBMTUSPLFPSOFVSPMPHJDEFBUI
BUEBZT
BUEBZT
TARGET
TARGET
RATERATE
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CBTFEPOFYUFOTJWFSFWJFXPGPVUDPNFTJO
DMJOJDBMMJUFSBUVSF
DMJOJDBMMJUFSBUVSF
PRIMARY
PRIMARY
SAFETY
SAFETY
ENDPOINT
ENDPOINT
DESCRIPTIONS
DESCRIPTIONS N
N % %
Hemorrhages
Hemorrhages
(parenchymal
(parenchymal
not SAH)
not SAH)
2
2 1.9 1.9
>50%>50%
stenosis
stenosis
with major
with major
strokestroke
1
1 0.9 0.9
Thrombosis
Thrombosis
with major
with major
strokestroke
2
2 1.9 1.9
H
H
Probable
Probable
neurologic
neurologic
deathdeath
1
1 0.9 0.9
TOTALTOTAL
6
6 5.6 5.6
— —PUFs
PUFs
achieved
achieved
high
high
rates
rates
of complete
of complete
aneurysm
aneurysm
occlusion
occlusion
(81.8%
(81.8%
at 180
at 180
days,
days,
85.7%
85.7%
at 1atyear)
1 year)
— —PUFs
PUFs
hadhad
reasonably
reasonably
lowlow
rates
rates
of major
of major
complications
complications
(5.6%
(5.6%
at 180
at 180
days)
days)
G. Includes
G. Includes
all patients
all patients
with attempted
with attempted
treatment.
treatment.
108 patients
108 patients
were enrolled.
were enrolled.
1 patient
1 patient
was excluded
was excluded
from from
analysisanalysis
becausebecause
of an access
of anfailure.
access 107
failure.
patients
107 patients
were included
were included
in the primary
in the primary
safety endpoint
safety endpoint
analysis.analysis.
H. Event
H. was
Event
classified
was classified
as probably
as probably
neurologic
neurologic
death ofdeath
unknown
of unknown
cause. No
cause.
headNoCThead
or autopsy
CT or autopsy
completed.
completed.
PRE-PROCEDURE
6 MONTHS FOLLOW-UP
1 YEAR FOLLOW-UP
3 YEAR FOLLOW-UP
Images courtesy of Tibor Becske, MD and Peter Kim Nelson, MD.
SOURCES
1
Tibor Becske, David Kallmes,Isil Saatchi, Cameron McDougall, Istvan Szikora, Giuseppe Lanzino, Christopher Moran, Henry Woo, Demetrius Lopes, Aaron Berez, Daniel Cher, Adnan Siddiqui, Elad Levy, Felipe
Albuquerque, David Fiorella, Zsolt Berentei, Saruhan Cekirge and Peter Kim Nelson. Pipeline Embolization Device for Uncoilable or Failed Aneurysms (PUFs) Results of a Multicenter Clinical Trial. Submitted March 2012
2
PUFs FDA Summary of Safety and Effectiveness Data (SSED)
3
The International Study of Unruptured Intracranial Aneurysms Investigators. Unruptured Intracranial Aneurysms – Risk of Rupture and Risks of Surgical Intervention. Neuroradiology. N Engl J Med 1998; 339:1725-1733
4
ISAT: International Subarachnoid Aneurysm Trial (ISAT) of neurosurgical clipping vs endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomized trial. The Lancet, Vol 360, Oct 2002
The Pipeline™ embolization device should be used only by physicians trained in percutaneous, intravascular techniques and procedures at medical facilities with the appropriate fluoroscopy equipment.
The Pipeline embolization device is indicated for the endovascular treatment of adults (22 years of age and older) with large or giant wide-necked intracranial aneurysms in the internal carotid artery from the petrous to
the superior hypophyseal segments.
CAUTION: Federal (USA) law restricts this device to sale, distribution and use by or on the order of a physician. Contraindications: The use of the Pipeline embolization device is contraindicated for patients with any of the
following conditions: 1) Patients with an active bacterial infection; 2) Patients in whom dual antiplatelet therapy (aspirin and clopidogrel) is contraindicated; 3) Patients who have not received dual anti-platelet agents prior
to the procedure; or 4) Patients in whom a pre-existing stent is in place in the parent artery at the target aneurysm location. WARNING: Persons with known allergy to platinum or cobalt/chromium alloy (including the major
elements Platinum, Cobalt, Chromium, Nickel or Molybdenum) may suffer an allergic reaction to the Pipeline embolization device.
Covidien
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