ESOC @ wagers TRAGE-III
Tenecteplase for Ischemic Stroke Due to Large
Vessel Occlusion at 4.5 to 24 Hours with Rentuslen
Imaging Selection
Yunyun Xiong and Yongjun Wang
for the TRACE-Il investigators
(NCT 05141305)
Department of Neurology,
Beijing Tiantan Hospital,
Capital Medical University
eso-conference.orgDisclosures
‘Competing)interests)
> Dr. Schwamm serves as a scientific consultant regarding trial design and conduct to Genentech and
Member of steering committee (TIMELESS NCT03785678); consultant on user interface design and
usabllity to Lifelmage; and a member of a Data Safety Monitoring Boards (DSMB) for Penumbra
(MIND NCT03342664).
> Dr. Fisher serves as a consultant for Simcere USA and Lumosa; and a member of DSMB for Moleac.
eS] elas
> National Natural Science Foundation of China
> Beijing Municipal Science & Technology Committee
> China Shijiazhuang Pharmaceutical Company Recomgen Pharmaceutical (Guangzhou) supplied
tenecteplase without charge
ESOC @> aes caeTenecteplase in Ischemic Stroke Trials =
NOR-TEST, Phase 3
Parsons, Phase 2b O.4mgfkg Tenecteplase ___AcT, Phase 3
0.25 maikg tenecteplase ‘was not superior to 0.25mg/kg tenecteplase_—_‘TRACE-2, Phase 3
was superior fo 0.1 mg/kg alteplase and showed a __isareasonable —_0.25mg/kg tenecteplase is,
tenecteplase similar safety alternative o alteplase _non-inferior to alteplase
Haley EC, Pilot dose- ATTEST, Phase 2 NOR-TEST 2 PartA, Phase 3
escalation study No diference between 0.4mg/kg Tenecteplase yeilded worse
Tenecteplase doses of 0.25mgikg tenecteplase ‘safety and functional outcomes
0.1 to 0.4 mg/kg are safe and alteplase compared with alteplase in moderate or
ischemic stroke severe stroke
IC ‘we yote or srnone
ESOC @ nae eso-conterence.orgLate Tenecteplase for Stroke Patients With
Large Vessel Occlusion?
‘The WEW ENGLAND JOURNAL of MEDICINE
ORIGINAL ARTICLE
Tenecteplase for Stroke at 4.5 to 24 Hours
with Perfusion-Imaging Selection
Sore onthe Modified Rankin Seal 29 Day
onl? 0) gems m6
is
uss | ae Ta)
(rezae}| eos) glade) (es
Percenage of Pent:
‘THE voIce oF stROKE
IweuROPE
Esoc &
TIMELESS 2.
‘A study of magingeterbn tous ontment
+ N=458
+ EVT performed: ~77%
* Comprehensive stroke center (median lytic
to puncture 16min)
* Shift analysis: aOR 1.13, 95% Cl 0.82-1.57
* sICH: 3.2% vs. 2.3%
esorconference.org
10:701-711.
N Engl J Med. 2024;Late Tenecteplase for Stroke Patients With |
Large Vessel Occlusion?
Global Thrombectomy Access
+ Median thrombectomy access was
2.79% global, and 21% in high
income countries
* Thrombectomy access is <1% in
27% of countries and 10% of
countries have no thrombectomy
access at all
+ The effect of late administration of
tenecteplase in patients without
immediate access to thrombectomy
is currently unknown
ce ca THE VOICE OF STROKE
ESOC hahaa Circulation. 2023;147:1208-1220. _ese-conterenceorgLate Tenecteplase for Stroke Patients With &
Large Vessel Occlusion?
Global Thrombectomy Access
+ Median thrombectomy access was
2.79% global, and 21% in high
income countries
+ Thrombectomy access is <1% in
27% of countries and 10% of
countries have no thrombectomy
access at all
+ The effect of late administration of
tenecteplase in patients without
immediate access to thrombectomy
is currently unknown
cenr {THe voice oF STROKE
ESOC @& menor. Circulation. 2023;147:1208-1220. _-6s
Mismatch volume: Hyperfusion
volume-core volume
Mismatch ratio: Hyperfusion
volume/core volume
NICE OF STROKE Neurol Ther. 2022;11:1777-1788.
ESOC GB esr SSroke Voss Neural, 024.omn-2629-002064, _earconencearsKey Exclusion Criteria TRACE ll Gps
+ Intention to proceed to endovascular treatment
+ Allergy to tenecteplase
+ NIHSS consciousness score 1a >2, or epileptic seizure, hemiplegia after
seizures (Todd's palsy) or other neurological/mental illness such that the
patient is not able to cooperate or unwilling to cooperate
+ Any contraindication to intravenous thrombolysis
+ Multiple arterial occlusion (bilateral MCA occlusion, MCA occlusion
accompanied with basilar occlusion, NB tandem carotid occlusion was
eligible)
THE VOICE OF STROKE
ESOC > Newt csorconterenceargIntervention and Control TRACE: Geass
Tenecteplase (0.25 mg/kg) is given as a single,
intravenous bolus (within 510 s) immediately |
on randomisation. Maximum dose is 25 mg.
Aspirin combined with clopidogrel, aspirin
alone, or clopidogrel alone after randomization
at the discretion of local neurologists. |
ESOC @ mame CoenOutcomes
Primary/Outcome)
MRS/score’S1/at 90 days (unadjusted)
Secondary The ordinal distribution of mRS at 90 days:
Outcomes
MRS score $2 at 90 days
Early neurological recovery at 72 hours (defined as a reduction of 28
points on NIHSS compared with baseline or a score of <1)
Reperfusion at 24 hours (defined as >90% reduction in Tmax >6s lesion
volume)
Change from baseline to 7-day NIHSS score
Safety Outcomes Symptomatic intracranial hemorrhage within 36 hours (ECASS II)
Death from any cause
Systemic bleeding within 90 days (GUSTO: moderate or severe bleeding)
Adverse events or severe adverse events within 90 daysSample Size
Aprespecified promising zone adaptive sample size re-estimation procedure
(Mehta and Pocock)*
Assumptions:
Standard medical treatment group mRS 0-1: 25%
Power: 80%
One-sided alpha of 0.025
Attrition rate of 10%
Minimum: 516 (12% difference), Maximum: 808 (9.5% difference)
Interim analysis (258 patients) determined no sample size increase was required
and the final sample size remained 516.
ESOC GD maison srrore ns
*Stat Med 2011;30:3267-3284.Results
esac
953 Wer ecb
ee fa inreereel henge
ready recived erombolie stan exter
211 Were tended to reeed to enerselst
‘+50 1ad npedesiy in>172 CA team
2726 Were wb prem or winerpeabe CTP
20 id echemie stoke or moc fein in
previous 3 months
> 16Notmecingtrget mismatch profile
‘on CTP er MRIOMR prison
ete beol ge 2802223 mat
any kaw impairment inconuaion
‘S16 Point vnerael randomization
264 Were sped to tereteplae and
252 Wereassgnedo sandard meio
treme andincaded inte
I
T
2 Were inca inthe fy popon
1252 Were inca inthe fy popusion
TRAGE-IIl
Time period: January,
2022, to November, 2023
Screening: 1469 patients
Enrolled: 516 patients
eso-conference.orgBaseline Characteristics
GIES
fenecteplase)
TRAGE “II ess
‘Standard Medical Treatment:
(N=264) (N=252)
Median age (IQR) — yr 67 (58-75) 68 (59-76)
Male sex — no. (%) 183 (69.3) 167 (66.3)
Hypertension’ 177 (67.1) 180 (71.4)
Diabetes mellitus 69 (26.1) 74 (28.2)
Atrial fibrillation 49 (18.6) 48 (19.1)
Median NIHSS score at admission — | 44 (7.45) 407-14)
(]QR)
Type of stroke onset — no. (%)
Known onset time 4143 (54.2) 149 (59.1)
Unwitnessed onset 20 (7.6) 19 (7.5)
Wake-up stroke 101 (38.3) 84 (33.3)Baseline Characteri
Cire etsttss
Median volume of ischemic core (IQR)
mi
Median volume of perfusion lesion
(QR) — mI
stics
Tener
(N=264)
119.1 (79.8-177.2) 123.2 (74.6-180.1)
16.4 (5.7-28.4)
—
TRAGE-I @3-
Renee ice rere tens
(N=252)
14.9 (6.0-29.3)
Occlusion site — no. (%)
randomization — hr
Internal carotid artery 87 (33.0) 84 (33.3)
Middle cerebral artery — M1 119 (45.1) 130 (51.6)
‘Middle cerebral artery — M2 58 (22.0) 38 (15.1)
Door-to-needle time — min. 139 (94-190) :
Time from symptom onset to 422(85-160) 42.4 (8517.5)
Endovascular treatment — no. (%)
4 (1.5)
5 (2.0)TRAGEMII Sa
THEWOICE OF stROKE
we eso-conferenceorgFree
Primary Outcome TRACE-I] Gb=ges
Modiied Rankin Seale Scoro
we
Tereza ” By
‘ose
ESOC > was —Primary Outcome
‘Moained Rankin Seale Score
. os
‘oat
Pane On Con ONE Lecee Ten Seireelmeriee! Relative|Riskyy||P)Values
(N=264) iTreatment(N=252) (95%1CI)
mRS <1 at 90 days | 87 (33.0) 61 (24.2) 1.37 (1.04-1.81) |0.03
* Two-sided P value
sac tHevoice or stRoKE
€soc IWeunore eso-conference.rgSecondary Outcomes
Standard)
ee Tenses | |iiecrect Effect size
(N=264) Treatment CaACiy
(N=252)
Ordinal distribution of mRS.
1.33 (0.98-1.81) 0.06
at 90 days
MRS s2 at 90 days 115 (43.6) 84 (33.3) 1.31 (1.05-1.63) 0.02
Early neurological recovery at 72
hours (1-499) 40/250 (16.0) | 15/249 (6.0) 2.66 (1.51-4.69) 0.001
herr 290% at 24 hours | 4g/939 (20.1) | 27/229 (11.8) 4.70 (1.10-2.64) 0.02
‘Change from baseline to 7-day
Nise score -4 (6 to-1) -2(-5 to 0) -1.47 (-2.30 to-0.64) | 0.001.
* Common odds ratio is shown for the ordinal score on mRS; B coefficient with its 95% Cl is shown for the outcome of NIHSS
change from baseline to 7-day, and Relative Risks are shown for other outcomes.Safety Outcomes
Safety outcomes
Tenecteplase
(N=264)
(Standard
NCL
Treatment
Relative Risk
CAC
Pyalue:
(N=252))
SICH within 36 hours * | 8 (3.0) 20.8) 3.82 (0.82-17.87) 0.09
Death within 90 days | 35 (13.3) 33 (13.1) 1.01 (0.65-1.58) 0.96
‘Severe or moderate
| systemic bleeding 5(1.9) 20.8) 2.36 (0.46-12.09) 0.07
‘Adverse events 134 (50.8) 129 (51.2) 0.99 (0.84-1.17) 0.89
Serious adverse events | 53 (20.1) 43,(17.1) 1.18 (0.82-1.69) 0.38
* ECASS Ill: any extravascular blood in the brain or within the cranium associated with clinical deterioration, defined by an
increase of 4 points or more on the NIHSS from the baseline or within 36 hours; or that led to death and that was identified as the
predominant cause of the neurological deterioration.
ESOC @ maser
‘eso-conference.org—
Subgroups TRA\ Ell Gees
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eso-conference.org—
Limitations TRACE mga
+ Open-label, blinded outcome
+ Results do not apply to patients who can immediately access thrombectomy
* Trial was performed in China where patients have a lower proportion of atrial
fibrillation than in Western countries
oar THE VOICE OF STROKE
€sac EUROPE eso-conferenceorgConclusions TRACE MII ges
Tenecteplase reduced disability for Chinese patients with LVO 4.5-24h after onset |
+ No safety concerns
— SICH 3% similar to TIMELESS and 0-4.5 hr trials
— no difference in mortality
The results apply to patients who cannot immediately access thrombectomy,
including those requiring interhospital transfer in whom there is no guarantee they
will remain eligible for EVT on arrivalomen)
Acknowledgement TRACE Gem
Thanks to TRACE-II trial participants, investigators, steering committee,
DSMB, core lab and event adjudication committee.
in revorce or sox
ESOC @> nage éAcknowledgement TRAGE-Il @bngexs
WYTRAGE-II
Thank you
—*
ESOC