THERAPY TRIAL
ESO CONFERENCE
GLASGOW, SCOTLAND
APRIL 17, 2015
J MOCCO1, OSAMA ZAIDAT2, RÜDIGER VON KUMMER3, ALBERT YOO4, RISHI
GUPTA5, DEMETRIUS LOPES6, DON FREI7, POOJA KHATRI8
FOR THE PENUMBRA THERAPY TRIAL
INVESTIGATORS
1MOUNT SINAI HEALTH SYSTEM, NEW YORK, 2MEDICAL COLLEGE OF WISCONSIN,
MILWAUKEE, WI, 3UNIVERSITÄTSKLINIKUM DRESDEN,DRESDEN, GERMANY,
4MASSACHUSETTS GENERAL HOSPITAL/HARVARD, BOSTON, MA, 5WELLSTAR HEALTH
SYSTEM, MARIETTA, GA, 6RUSH UNIVERSITY, CHICAGO, IL, 7SWEDISH MEDICAL CENTER,
DENVER, CO, 8UNIVERSITY OF CINCINNATI, CINCINNATI, OH.
Personal Disclosures
• NIH:
• NIH 1U01NS086492-01 (CO-PI)
• NIH 1R01NS078828-01A1 (CO-Inv)
• National/International PI/Co-PI:
• COAST (Co-PI)
• THERAPY (PI)
• FEAT (PI)
• LARGE (Co-PI)
• POSITIVE (Co-PI)
• Steering Committee: MAPS
• Consultant: Lazarus Effect, Medina, Pulsar, Edge Therapeutics
• Investor: Blockade Medical, Medina Medical, Lazarus Effect
• Advisory Board: Codman Neurovascular
THERAPY Trial
Trial Disclosures
THERAPY funded by Penumbra, Inc.
THERAPY Trial
THERAPY Background
THERAPY sought to evaluate
the Penumbra System in a population
of LVO patients thought to be particularly
at risk for poor outcome from IV tPA
®
Clot length > 8mm from thin-sliced NCCT
THERAPY Trial
Study Design
Prospective, RCT, randomized 1:1
Control: Monotherapy IV rtPA
Intervention: Combined IV rtPA + IA Penumbra System
692 patients to be enrolled at up to 75
centers
Powered by an expected 10.6% absolute
difference in 90 day mRS 0-2
1, 2, 3
1.Bhatia R, Hill MD, Shobha N, et al. Low Rates of acute recanalization with intravenous recombinant tissue plasminogen activator in ischemic stroke:
Real-world experience and a call for action. Stroke. 2010;41:2254-2258.
2.Tarr R, Hsu D, Kulcsar Z, et al. The POST Trial: Initial post-market experience of the Penumbra System. Revascularization of large vessel occlusion
in acute ischemic stroke in the United States and Europe. J Neurointerv Surg. 2010;2:341-344.
3.Penumbra Pivotal Stroke Trial Investigators. The Penumbra Pivotal Stroke Trial: Safety and effectiveness of a new generation of mechanical devices
for clot removal in intracranial large vessel occlusive disease. Stroke. 2009;40:2761-2768.
THERAPY Trial
Study Design
Enrollment halted on October 29, 2014
108 patients enrolled
Trial halted by steering committee secondary to
external evidence from MR CLEAN, EXTEND IA,
and ESCAPE that indicated a lack of equipoise.
Not due to DSMB review of data for evaluation of
stopping rules.
THERAPY Trial
Study Design
Patient presents with acute ischemic stroke
from LVO within 4.5hrs from onset, treated
with IV rtPA
Informed Consent, Screened for eligibility,
>8mm clot length from thin-sliced NCCT,
IA initiated within 5 hours, Randomized 1:1
Monotherapy IV rtPA
Combined IV rtPA + IA
Penumbra
24 Hour and 7
Day/Discharge
24 Hour and 7
Day/Discharge
30 Day Follow Up
30 Day Follow Up
90 Day Follow Up
90 Day Follow Up
THERAPY Trial
Pre Specified Endpoints
Efficacy (ITT and PP)
Primary
Good functional outcome at 90 days
follow-up as defined by a mRS of 02
Secondary
Ordinal improvement in 90-day mRS
Good clinical outcome at 30 days
post-procedure*
24-hour infarct volume
Safety
Primary
Incidence of serious adverse
events up to 90 days from
enrollment
Secondary
Mortality
Incidence of symptomatic and
asymptomatic hemorrhage
*Good clinical outcome at 30 days post-procedure as defined by a 10
points or more improvement in the NIHSS at Discharge, NIHSS score
or 0-1 at Discharge; or a 30-day mRS score of 0-2.
Note: All primary and secondary efficacy endpoints pre-specified for both
THERAPY Trial
the intent-to-treat (ITT) population and per-protocol (PP) population.
Blinded Core Lab Assessments
Imaging:
• mTICI reperfusion scores
• ASPECTS
• MCA territory infarct size
• Intracerebral hemorrhage (ICH)
• Clot Length
Clinical Outcomes:
• Video adjudication of Modified Rankin Score (mRS)
THERAPY Trial
mRS Video Assessments
• In-person visit recorded using study camcorder
• Standard interview questionnaire for data reliability
1,2,3
• Rankin Focused Assessment Tool (RFAT)
• Independent blinded adjudication
• HIPAA compliant
1.Saver JL, Filip B, Hamilton S, et al. Improving the reliability of stroke disability grading in clinical trials and clinical practice: the Rankin Focused Assessment (RFA). Stroke. 2010;41:992-995.
2.Quinn TJ, McArthur K, Dawson J, Walters MR, Lees KR. Reliability of structured modified rankin scale assessment. Stroke. 2010;41:e602.
3.Quinn TJ, McArthur K, Dawson J, Walters MR, Lees KR. Reliability of structured modified rankin scale assessment. Stroke. 2010; 41:e603.
THERAPY Trial
Trial Organization
Academic Steering
Committee
J Mocco, MD, MS
Mount Sinai Health System, USA
Pooja Khatri, MD, MSc
University of Cincinnati, USA
Osama Zaidat, MD, MSc
Medical College of Wisconsin, USA
Prof. Dr. med. Rüdiger
von Kummer
Universitätsklinikum Carl Gustav Carus
Technical University
of Dresden, Germany
Core Labs
CEC and DSMB
Albert Yoo, MD
Imaging Core Lab
Thanh Nguyen, MD
Boston University, USA
Massachusetts General Hospital, USA
Darren Orbach, MD, PhD
Randy Edgell, MD
US mRS Adjudicator
The Univ of Texas HS Center, USA
Boston Children’s Hospital, USA
William Mack, MD
University of Southern California, USA
Prof. Dr. med. E. Bernd
Ringelstein
EU mRS Adjudicator
University Hospital Münster, Germany
Scott Hamilton, PhD
Stanford University School
of Medicine, USA
Rishi Gupta, MD, MBA
Wellstar Health System, USA
THERAPY Trial
Participating Centers
US Centers
Patients enrolled / planned sample size
Enrolling / Activated
EU Centers
108 / 692
36 / 48
THERAPY Trial
Inclusion Criteria
• 18 - 85 years of age
• IV tPA treated
• CTA confirmed Large Vessel Occlusion (LVO)
• Clot length > 8mm
• Anterior circulation (ICA, M1, M2)
• NIHSS > 8
• Signed informed consent
THERAPY Trial
Exclusion Criteria
• History of stroke in the past 3 months
• Females who are pregnant
• Pre-stroke mRS score >2
• Known severe allergy to contrast media
• Uncontrolled hypertension (systolic blood pressure >185 mmHg
or diastolic blood pressure >110 mmHg)
• CT evidence of the following conditions at randomization:
• Significant mass effect with midline shift
• Acute ischemic changes in >1/3 of the affected middle cerebral
artery territory
• Evidence of intracranial hemorrhage
THERAPY Trial
Exclusion Criteria
• Angiographic evidence of tandem extracranial
occlusion or an arterial stenosis proximal to the
occlusion that requires treatment prior to thrombus
removal
• Angiographic evidence of preexisting arterial injury
• Rapidly improving neurological status prior to
randomization
• Bilateral stroke
• Intracranial tumors
• Known history of cerebral aneurysm or
arteriovenous malformation
THERAPY Trial
RESULTS
THERAPY Trial
Randomization and Follow-up
Randomized
(n=108)
Allocation:
Penumbra System + IV tPA (n=55)
90 Day Follow-Up
Final Evaluation n=50:
Final Evaluation not available n=5:
- Lost to follow-up* n=3
- Withdrew consent n=2
Allocation:
IV tPA alone (n=53)
90 Day Follow-Up
Final Evaluation n=46:
Final Evaluation not available n=7:
- Lost to follow-up* n=5
- Withdrew consent n=2
*If there is no response after 3 failed attempts to contact the patient, the site mails a certified letter
to the patient’s last known address.
THERAPY Trial
Baseline Characteristics: Demographics
Variable
IA + IV
IV Alone
Age, mean
67.4
70.1
(SD)
(11.4)
(10.3)
38.2%
56.6%
(21/55)
(30/53)
17
18
[13,22]
[14,22]
110.5
116.0
[99.0,151.0]
[103.0,133.0]
148.2
150.4
(22.3)
(19.1)
Female
Admission NIHSS,
median [IQR]
Glucose mg/dL,
median [IQR]
Systolic BP mmHg,
mean (SD)
p-value
0.2257
0.0823
0.4254
0.9305
0.4664
THERAPY Trial
Baseline Characteristics: Medical History
Characteristics
Previous stroke
Previous transient ischemic
attack (TIA)
Myocardial infarction
Angina/CAD
Hypertension
CHF (congestive heart failure)
Dyslipidemia
Diabetes
Atrial fibrillation
Peripheral artery disease
Extracranial cerebral artery
disease
Current or former smoker
IA + IV
(N=55)
9.6%
IV Alone
(N=53)
7.5%
6.1%
3.8%
0.6692
8.0%
29.1%
77.8%
13.2%
43.4%
32.1%
30.9%
2.0%
1.9%
15.1%
78.8%
7.7%
49.0%
37.3%
49.1%
3.8%
0.1964
0.1058
1.0
0.5260
0.6942
0.6810
0.0765
1.0
8.3%
11.5%
0.7429
59.6%
38.8%
0.0655
p-value
0.7415
THERAPY Trial
Imaging Characteristics
Characteristica
IA + IV
60.0%
IV Alone
58.5%
(33/55)
(31/53)
Intracranial ICA
32.7%
22.6%
(18/55)
(12/53)
MCA M1
56.4%
67.9%
(31/55)
(36/53)
MCA M2
10.9%
9.4%
(6/55)
(5/53)
7.5
8.0
[6.0,9.0]
[7.0,9.0]
0 to 4
11.1%
7.5%
(6/54)
(4/53)
5 to 7
38.9%
35.8%
(21/54)
(19/53)
8 to 10
50.0%
56.6%
(27/54)
(30/53)
12.9
14.1
[9.4,22.2]
[10.1,18.6]
Location of stroke: Left hemisphere
p-value
1.0
Site of primary occlusion
ASPECTS, median
(IQR)
Clot length, median
(IQR)
a
As adjudicated by the core laboratory; imaging ASPECTS not available for 1 subject
0.4365
0.4867
0.7140
0.8925
THERAPY Trial
Key Time Metrics (minutes)
64 [40,133] a
Onset to ED
57 [30,118] a
108 [86,138] a
Onset to IV tPA
102 [80,154] a
181 [129,221] a
Onset to Randomization
169 [132,224] a
123 [80,166] a
CT to Groin Puncture
226 [184,263] a
Onset to Groin Puncture b
0
50
100
150
200
250
a
Median [IQR]
b Initial protocol allowed up to 8 hours,
protocol revision for up to 5 hours (6.5% were > 5 hours)
IA+IV
IV Alone
THERAPY Trial
Devices Used
Separator: 54%
Separator 3D: 25%
Ace: 27%
Ace64: 0%
Other: 13%
THERAPY Trial
Core Lab Assessed Reperfusion Results
60%
mTICI Score
51%
Patients (%)
50%
IA + IV
mTICI 2/3
after Penumbra System®
86%
mTICI 2b/3
after Penumbra System
70%
Final mTICI 2b/3
after additional treatment
73%
Patients with additional
treatmenta
13%
40%
30%
20%
10%
19%
16%
7%
7%
0%
a
0
1
2a
2b
Use of Solitaire or Trevo in 7 patients
3
mTICI after Penumbra System
THERAPY Trial
SAFETY OUTCOME
THERAPY Trial
Safety Outcomes: As Treated
Outcome
IA + IV
IV Alone
42%
48%
(18/43)
(30/62)
12.0%
23.9%
(6/50)
(11/46)
9.3%
9.7%
(4/43)
(6/62)
p-value
Primary Endpoint:
Serious Adverse Event at 90 days
0.55
Pre-Specified Secondary Endpoints:
Mortality at 90 days (ITT)
Symptomatic ICH - Core Lab with ≥ 4 point
change in NIHSS
0.1811
1.0
THERAPY Trial
INTENT TO TREAT EFFICACY:
PRE-SPECIFIED
THERAPY Trial
Efficacy Outcomes: Intent to Treat
Outcome
IA + IV
IV Alone
p-value
38%
30%
(19/50)
(14/46)
0.44
Primary Endpoint:
mRS 0-2 at 90 days
THERAPY Trial
Efficacy Outcomes: Intent to Treat
IA + IV
Outcome
IV Alone
p-value
Primary Endpoint:
Unadjusted Ordinal Outcome Analyses
0.5206
mRS 0-2 at 90 days
38.0%
30.4%
(19/50)
(14/46)
Secondary
Endpoint: ITT Ordinal mRS
Pre-Specified Secondary Endpoint: Ordinal mRS
IV Alone
IA + IV
2.2%
13.0%
6.0%
0.0%
15.2%
20.0%
10.0%
15.2%
12.0%
20.0%
30.0%
21.7%
16.0%
40.0%
50.0%
8.7%
23.9%
30.0%
60.0%
70.0%
4.0% 12.0%
80.0%
90.0%
100.0%
OR 1.76 (95% CI: 0.86 to 3.59) p-value = 0.1216
Secondary Endpoint: PP Ordinal mRS
THERAPY Trial
Efficacy Outcomes: Intent to Treat
Outcome
IA + IV
IV Alone
p-value
38.0%
30.4%
(19/50)
(14/46)
0.5206
45.3%
32.1%
(24/53)
(17/53)
26.0%
15.2%
(13/50)
(7/46)
6.0
1.0
[-3.0,11.0]
[-1.0,9.0]
40.9%
29.5%
(18/44)
(13/44)
Primary Endpoint:
mRS 0-2 at 90 days
Pre-specified Secondary Endpoint:
Good outcome at 30 daysa
0.2313
Additional Outcomes:
mRS 0-1 at 90 days
NIHSS improvement at 24 hours,
median [IQR]
NIHSS 0 to 2 at 90 days
0.2182
0.3036
0.3722
a. Good clinical outcome at 30 days post-procedure as defined by a 10 points or more improvement in the NIHSS
at Discharge, NIHSS score or 0-1 at Discharge; or a 30-day mRS score of 0-2.
THERAPY Trial
PER-PROTOCOL EFFICACY:
PRE-SPECIFIED
THERAPY Trial
Per-Protocol Enrollment
Randomized
(n=108)
Allocation:
Penumbra System + IV tPA (n=55)
Allocation:
IV tPA alone (n=53)
Per-Protocol Enrollment n=43
Excluded from Per-Protocol analysis n=12
- Stenosis proximal to occlusion that requires
treatment prior to thrombus removal (n=5)
- Infarct > 1/3 MCA territory (n=5)
- Pre-existing neurologic deficit (n=1)
- Clot length < 8mm (n=1)
Per-Protocol Enrollment n=47
Excluded from Per-Protocol analysis n=6
- Stenosis proximal to occlusion that requires
treatment prior to thrombus removal (n=1)
- Infarct > 1/3 MCA territory (n=4)
- Pre-existing neurologic deficit (n=1)
90 Day Follow-Up
Final endpoint data available n=41
Final endpoint data not available n=2
- Lost to follow-up n=2
90 Day Follow-Up
Final endpoint data available n=41
Final endpoint data not available n=6
- Lost to follow-up n=4
- Withdrew consent n=2
THERAPY Trial
Efficacy Outcomes: Per-Protocol
Outcome
IA + IV
IV Alone
41.5%
29.3%
(17/41)
(12/41)
p-value
Primary Endpoint:
mRS 0-2 at 90 days
0.3557
THERAPY Trial
Secondary Endpoint: ITT Ordinal mRS
2.2%
IV Alone
13.0%
15.2%
15.2%
21.7%
8.7%
23.9%
Efficacy Outcomes: Per-Protocol
IA + IV
Outcome
IA + IV
6.0%
20.0%
12.0%
IV Alone
16.0%
p-value
30.0%
4.0% 12.0%
Primary Endpoint:
10.0%
mRS 0.0%
0-2 at 90
days
20.0%
30.0%
40.0%
41.5%
50.0%
29.3%70.0%
60.0%
(17/41)
(12/41)
80.0%
0.3557
90.0%
100.0%
OR 1.76 (95% CI: 0.86 to 3.59) p-value = 0.1216
Pre-Specified Secondary Endpoint: Ordinal mRS
Secondary Endpoint: PP Ordinal mRS
2.4%
IV Alone
IA + IV
a
0.0%
12.2%
8.1%
14.6%
17.1%
21.6%
10.0%
20.0%
10.8%
30.0%
19.5%
21.6%
40.0%
50.0%
9.8%
24.4%
24.3%
60.0%
70.0%
OR 2.25 (95% CI: 1.01, 5.00) p-value = 0.047
5.4%
80.0%
8.1%
90.0%
THERAPY Trial
100.0%
Efficacy Outcomes: Per-Protocol
Outcome
IA + IV
IV Alone
41.5%
29.3%
(17/41)
(12/41)
51.2%
34.0%
(22/43)
(16/47)
29.3%
14.6%
(12/41)
(6/41)
6.0
1.0
[-2.0,10.5]
[-2.0,9.0]
47.2%
30.0%
(17/36)
(12/40)
p-value
Primary Endpoint:
mRS 0-2 at 90 days
0.3557
Pre-Specified Secondary Endpoint:
Good outcome at 30 daysa
0.1352
Additional Outcomes:
mRS 0-1 at 90 days
NIHSS improvement at 24 hours,
median [IQR]
NIHSS 0 to 2 at 90 days
0.1813
0.2359
0.1580
a. Good clinical outcome at 30 days post-procedure as defined by a 10 points or more improvement in the NIHSS
at Discharge, NIHSS score or 0-1 at Discharge; or a 30-day mRS score of 0-2.
THERAPY Trial
Discussion
Early termination secondary to MR CLEAN,
ESCAPE, EXTEND-IA severely limits data
interpretation
Natural imbalances occur in small cohorts
THERAPY Trial
Discussion
Early termination secondary to MR CLEAN,
ESCAPE, EXTEND-IA severely limits data
interpretation
Natural imbalances occur in small cohorts
THERAPY Trial
Discussion
Early termination secondary to MR CLEAN,
ESCAPE, EXTEND-IA severely limits data
interpretation
Natural imbalances occur in small cohorts
Pre-specified Secondary Outcome:
Multivariable adjusted ordinal analysis
ITT: OR 2.4, 95% CI 1.1,5.1; p-value=0.02
PP: OR 2.4, 95%CI: 1.1,5.8; p-value=0.03
THERAPY Trial
Discussion
THERAPY used unique selection criteria
Impact is difficult to asses across this small population
THERAPY Trial
Discussion
THERAPY used unique selection criteria
Impact is difficult to asses across this small population
Symptomatic ICH
IA + IV
Symptomatic ICH
IV Alone
3.6%
2.7%
SWIFT-PRIME (n=196)
1%
3.1%
EXTEND IA (n=70)
0%
6%
MR CLEAN (n=500)
7.7%
6.4%
THERAPY (n=108)
10.9%
11.3%
Study
ESCAPE (n=315)
THERAPY Trial
Discussion
THERAPY used unique selection criteria
Impact is difficult to asses across this small population
Symptomatic ICH
IA + IV
Symptomatic ICH
IV Alone
3.6%
2.7%
SWIFT-PRIME (n=196)
1%
3.1%
EXTEND IA (n=70)
0%
6%
MR CLEAN (n=500)
7.7%
6.4%
THERAPY (n=108)
10.9%
11.3%
Study
ESCAPE (n=315)
THERAPY Trial
Discussion
THERAPY used unique selection criteria
Impact is difficult to asses across this small population
Symptomatic ICH
IA + IV
Symptomatic ICH
IV Alone
3.6%
2.7%
SWIFT-PRIME (n=196)
1%
3.1%
EXTEND IA (n=70)
0%
6%
MR CLEAN (n=500)
7.7%
6.4%
THERAPY (n=108)
10.9%
11.3%
2.3%
4.8%
Study
ESCAPE (n=315)
THERAPY using Swift Prime Definition
THERAPY Trial
Discussion
However, despite being underpowered
THERAPY demonstrates consistent suggestion
of superiority for the endovascular arm
THERAPY Trial
Discussion
Pre-specified PP analysis of ordinal mRS
OR 2.25 95% CI (1.0, 5.0) p-value=0.047
Pre-specified adjusted ITT analysis of ordinal mRS
OR 2.4
95% CI (1.1, 5.1) p-value=0.02
Pre-specified adjusted PP analysis of ordinal mRS
OR 2.4
95% CI (1.1, 5.8) p-value=0.03
Data demonstrate an effect size indicating benefit for
the endovascular arm across all measured parameters
THERAPY Trial
Internal Validity: general trend in data
IA Worse
IA Better
Prespecified Primary
and Secondary
Endpoints
THERAPY Trial
External Validity
THERAPY’s relative effect size is
consistent with MR CLEAN and other
recent early-terminated trials
THERAPY Trial
Endovascular Trials: Mortality (ITT)
30%
24%
25%
20%
20%
19%
18%
19%18%
16%
15%
12%
10%
9%
10%
12%
9%
5%
0%
a
ESCAPE
a
SWIFT
PRIME
ESCAPE adjusted analysis p<0.05
EXTEND-IA REVASCAT MR CLEAN THERAPY
IA+IV
IV Alone
THERAPY Trial
Endovascular Trials: Mortality (ITT)
30%
24%
25%
20%
20%
19%
18%
19%18%
16%
15%
12%
10%
9%
10%
12%
9%
5%
0%
a
ESCAPE
a
SWIFT
PRIME
ESCAPE adjusted analysis p<0.05
EXTEND-IA REVASCAT MR CLEAN THERAPY
IA+IV
IV Alone
THERAPY Trial
Endovascular Trials: Ordinal mRS
IA Worse
IA Better
THERAPY Trial
Endovascular Trials: Ordinal mRS
IA Worse
IA Better
THERAPY Trial
Endovascular Trials: Ordinal mRS
IA Worse
IA Better
THERAPY Trial
Conclusion
While limited due to small sample size
following early termination, THERAPY
demonstrates a consistent direction towards
benefit across all outcome measures and an
effect size comparable with current modern
thrombectomy trials
THERAPY Trial
Enrolling Centers
United States
Europe
Site
Investigator
Rush University
Swedish Medical Center
Central DuPage Hospital
University of Cincinnati
Kaiser Los Angeles
St. Joseph's Regional Medical Center
Riverside Methodist Hospital
Vanderbilt
Sunrise Hospital and Medical Center
St. Joseph’s BNI
Erlanger Health System
Lutheran Medical Center
Medical College of Wisconsin
University of Chicago Medical Center
Miami Valley
Jackson Memorial Hospital
Cedars-Sinai
The Valley Hospital
Methodist Hospital
Forsyth Medical Center
Sparrow Hospital
JFK Medical Center
Alexian Brothers
Holy Cross
WellStar Research Institute
Shands at University of Florida
Abbott Northwestern
UCSD
Kaleida Health
Grady Memorial Hospital
Lehigh Valley Hospital
Stony Brook Medical Center
Demetrius Lopes
Don Frei
Harish Shownkeen
Aaron Grossman
Zahra A. Ajani
Dorothea Altschul
Ron Budzik
J.Mocco
Lindsey Blake
Cameron McDougall
Blaise Baxter
Jeffrey Farkas
Brian Fred Fitzsimmons
Seon Kyu Lee
John Terry
Dileep Yavagal
Michael Alexander
Dorothea Altschul
David Chiu
Don Heck
Syed Hussain
Jawad Kirmani
Tim Malisch
Laszlo Miskolczi
Rishi Gupta
Spiros Blackburn
Josser Delgado
Alexander Khalessi
Elad Levy
Raul Nogueira
Christian Schumacher
Henry Woo
Site
Universitätsklinikum Dresden
Universitätsmedizin Göttingen
Universitätsklinikum Aachen
Charité Berlin
Investigator
Rüdiger von Kummer
Michael Knauth
Martin Wiesmann
Christian Nolte
THERAPY Trial
THANK YOU
THERAPY Trial
ASPECTS Analysis
Core Lab Determined (ITT)
Variable
IA + IV
Day 90 mRS 0-2
IV Alone
Day 90 mRS 0-2
0%
33.3%
(0/4)
(1/3)
42.2%
30.2%
(19/45)
(13/43)
ASPECTS 0 to 4
ASPECTS 5 to 10
p-value*
0.2514
*p-value from logistic regression treatment interaction
**IA+IV group unable to read ASPECTS in 1 subject
THERAPY Trial
Exploratory Analysis:
mTICI and Outcome (ITT)
mTICIa
mTICI 0 to 2a
after Penumbra System
IA + IV
Day 90 mRS 0-2
p-value
9%
0.0668
mTICI 2b to 3
after Penumbra System
a
42%
As adjudicated by the core laboratory
THERAPY Trial
Pre-specified Subgroups (ITT)
Group
Age
< 65
≥ 65
NIHSS
< 20
≥ 20
Occlusion Location
ICA
M1
M2
Geographic Location
US
Europe
a
IA + IV
IV Alone
Day 90 mRS 0-2 Day 90 mRS 0-2
N = 50
N = 46
p-valuea
41.2% (7/17)
36.4% (12/33)
45.5% (5/11)
25.7% (9/35)
0.3101
32.3% (10/31)
47.4% (9/19)
38.5% (10/26)
20.0% (4/20)
0.1793
26.7% (4/15)
34.5% (10/29)
83.3% (5/6)
10.0% (1/10)
33.3% (11/33)
66.7% (2/3)
0.4946
36.4% (16/44)
50.0% (3/6)
27.9% (12/43)
66.7% (2/3)
0.9958
p-value from logistic regression treatment interaction
THERAPY Trial
Intracranial ICA occlusion percentage
Intracranial ICA
IA + IV
Intracranial ICA
IV Alone
27.6% (with M1)
26.5% (with M1)
18.3%
16%
EXTEND IA (n=70)
31%
31%
MR CLEAN (n=500)
25.7% (with/without M1)
29.3% (with/without M1)
THERAPY (n=108)
32.7%
22.6%
Study
ESCAPE (n=315)
SWIFT-PRIME (n=196)
THERAPY Trial
Pre-specified Endpoint: Ordinal mRS (ITT)
mRS at 90 days
2.2%
IV Alone
13.0%
IA + IV a 6.0%
0.0%
15.2%
20.0%
10.0%
mRS 0
15.2%
12.0%
20.0%
30.0%
mRS 1
16.0%
40.0%
mRS 2
a
21.7%
50.0%
mRS 3
8.7%
23.9%
30.0%
60.0%
70.0%
mRS 4
4.0%
80.0%
mRS 5
12.0%
90.0%
100.0%
mRS 6
OR 1.76 (95% CI: 0.86 to 3.59)
THERAPY Trial
Pre-specified Endpoint: Ordinal mRS (PP)
mRS at 90 days
2.4%
IV Alone
12.2%
IA + IV a 7.3%
0.0%
14.6%
17.1%
22.0%
10.0%
mRS 0
20.0%
mRS 1
12.2%
30.0%
40.0%
mRS 2
a
19.5%
9.8%
19.5%
50.0%
mRS 3
24.4%
26.8%
60.0%
70.0%
mRS 4
4.9% 7.3%
80.0%
mRS 5
90.0%
100.0%
mRS 6
2.28 OR 95% CI (1.05, 4.96)
p value = 0.0384
THERAPY Trial