Stroke: Vascular and Interventional Neurology

ORIGINAL RESEARCH

TESLA Trial: Rationale, Protocol, and

Design
Osama O. Zaidat, MD, MS † ; Sami Al Kasab, MD; Sunil Sheth, MD; Santiago Ortega-Gutierrez, MD, MSc;
Ansaar T. Rai, MD; Curtis A. Given II; Ramesh Grandhi, MD; Maxim Mokin, MD, PhD; Jeffrey M. Katz, MD;
Alberto Maud, MD; Rishi Gupta, MD; Wade S. Smith, MD,PhD; Diederik W. Dippel, MD, PhD; Daryl Gress, MD;
Thanh N. Nguyen, MD; Scott Brown; Ashutosh P. Jadhav, MD, PhD; Lucas Eljovich, MD; Charles Majoie, MD;
Mary S. Patterson; Hannah Slight; Kristine Below; Albert J. Yoo, MD, PhD †

BACKGROUND: Mechanical thrombectomy has been shown to be effective in patients with acute ischemic stroke secondary to
large-vessel occlusion and small to moderate infarct volume. However, there are no randomized clinical trials for large-core
infarct volume comparing mechanical thrombectomy to medical therapy in the population selected based solely on noncontrast
computed tomography brain scan. The TESLA (Thrombectomy for Emergent Salvage of Large Anterior Circulation Ischemic
Stroke) randomized clinical trial is designed to address this clinical question.
METHODS: The TESLA trial aim is to demonstrate the efficacy (3-month and 1-year disability following stroke) and safety of intraar-
terial mechanical thrombectomy in patients with large-volume infarction assessed with a noncontrast computed tomography
scan. The TESLA trial design is a prospective, randomized controlled, multicenter, open-label, assessor-blinded anterior circu-
lation acute ischemic stroke trial with adaptive enrichment design, enrolling up to 300 patients. Patients with anterior circulation
large-vessel occlusion who meet the imaging and clinical eligibility criteria with a large-core infarction on the basis of noncontrast
computed tomography Alberta Stroke Program Early CT Score (2–5) adjudicated by a site investigator will be randomized in a
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1:1 ratio to undergo intraarterial thrombectomy or best medical management up to 24 hours from last known well.
RESULTS: The primary efficacy outcome is utility-weighted modified Rankin Scale (mRS) score distribution at 90 days between
the groups. The results will be based on an intention-to-treat analysis that will examine the Bayesian posterior probability that,
adjusted for Alberta Stroke Program Early CT Score, patients with large-core infarct volume treated with intra-arterial thrombec-
tomy have higher expected utility-weighted mRS than those treated with best medical management alone. The primary safety
outcome is the 90-day death rate. Key secondary outcomes are dichotomized mRS 0 to 2 and 0 to 3 outcomes, ordinal
mRS scores, and quality of life (EuroQol 5 Dimension 5 Level survey) at 90 days and 1 year, utility-weighted mRS at 1 year,
hemicraniectomy rate, and rate of 24-hour symptomatic intracranial hemorrhage in both groups.
CONCLUSION: TESLA is a pragmatic trial, designed to address the unanswered question of the efficacy and safety of intra-arterial
thrombectomy in patients with large infarcts diagnosed by the site investigator only on noncontrast computed tomography scan
secondary to anterior circulation large-vessel occlusion up to 24 hours from stroke symptoms onset.

Key Words: clinical trial  design  large-core infarct  large-vessel occlusion  stroke  TESLA trial  thrombectomy

Correspondences to: Albert J. Yoo, MD, PhD, Texas Stroke Institute, Dallas, TX 75075. E-mail: ajyoo74@gmail.com
This manuscript was sent to Dr. Andrei V. Alexandrov, Guest Editor, for review by expert referees, editorial decision, and final disposition.
†
O.O. Zaidat and A.J. Yoo are co-first authors and contributed equally to the design and conduct of the study, Registration: ClinicalTrials.gov Identifier: NCT03805308,
FDA Investigational Device Exemption: G190006
© 2023 The Authors. Published on behalf of the American Heart Association, Inc., and the Society of Vascular and Interventional Neurology by Wiley Periodicals
LLC. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction
in any medium, provided the original work is properly cited and is not used for commercial purposes.
Stroke: Vascular and Interventional Neurology is available at: www.ahajournals.org/journal/svin

Stroke Vasc Interv Neurol. 2023;3:e000787. DOI: 10.1161/SVIN.122.000787 1

 Zaidat et al The TESLA Trial

ecent randomized intraarterial treatment tri-

R als demonstrated that intra-arterial thrombec-

tomy (IAT) improves clinical outcome in selected
patients with acute ischemic stroke (AIS) who present
Nonstandard Abbreviations and Acronyms
AIS acute ischemic stroke
with emergent large-vessel occlusions within 0 to ASPECTS Alberta Stroke Program
24 hours from stroke onset.1–6 The MR CLEAN (Multi- Early CT Score
center Randomized Clinical Trial of Endovascular Treat- BMM best medical manage-
ment for Acute Ischemic Stroke in the Netherlands) ment
trialists reported that this benefit was maintained at DSMB Data Safety Monitoring
2 years.7 Board
Although these randomized controlled trials (RCTs) FDA Food and Drug Admin-
used varying selection criteria, a meta-analysis of these istration
RCTs showed that the treatment benefit extended IAT intra-arterial thrombec-
broadly to the majority of patient subgroups.8 Subse- tomy
quently, 2 RCTs established the benefit of IAT in care- IV-rtPA intravenous recom-
fully selected patients beyond 6 hours, with an upper binant tissue-type
limit of 16 hours in 1 trial and 24 hours in the other.9,10 plasminogen activator
However, guidelines acknowledge that numerous ques- LCI large-core infarct
tions remain regarding how best to deliver this treat- MR CLEAN Multicenter Random-
ment, including whether patients with Alberta Stroke ized Clinical Trial
Program Early CT Score (ASPECTS) <6 would ben- of Endovascular
efit from IAT. Specifically, these early- and late-time- Treatment for Acute
window RCTs avoided patients with large-core infarct Ischemic Stroke in the
(LCI) volume, by excluding patients with ASPECTS Netherlands
<6, or computed tomography (CT) perfusion-estimated mRS modified Rankin Scale
core infarct >50 to 70 cc. As a result, these trials did not mTICI modified Thrombolysis
answer the question: What is the baseline infarct vol- in Cerebral Infarction
ume above which the clinical benefit of IAT is lost or cost NCCT noncontrast computed
ineffective?6 Moreover, the very low numbers needed tomography
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to treat for benefit (2.8–3.6 for 90-day modified Rankin NIHSS National Institutes of
Scale [mRS] score 0–2) attest to the likelihood that Health Stroke Severity
there are more patients outside of the current guideline- Scale
recommended treatment population who might benefit RESCUE-Japan LIMIT Recovery by Endovas-
by identifying the core infarct volume beyond which IAT cular Salvage for
is not beneficial.11 This is confirmed by a single-center Cerebral Ultra-Acute
cohort study that reported that a very low percentage Embolism–Japan Large
(1.7%) of patients with stroke satisfy currently published Ischemic Core Trial
RCT criteria.12 The TESLA (Thrombectomy for Emer- TENSION Efficacy and Safety
gent Salvage of Large Anterior Circulation Ischemic of Thrombectomy in
Stroke) randomized clinical trial is designed to address Stroke With Extended
this clinical question. For TESLA, the primary imag- Lesion and Extended
ing modality for patient selection is noncontrast CT Time Window
(NCCT) brain scan, using ASPECTS for determination TESLA Thrombectomy for
of infarct volume. This choice is intended to enhance Emergent Salvage of
the pragmatic design and generalizability of the TESLA Large Anterior Cir-
trial worldwide. culation Ischemic
Stroke

TRIAL DESIGN AND METHODS

Trial Objectives
The trial primary objective is to establish the effec-
tiveness and safety of IAT (versus best medical man-
agement [BMM] alone) in patients with large baseline
infarcts (defined by NCCT ASPECTS 2–5), with adap-
tive enrichment to better define the upper limit of infarct
volume for treatment benefit in anterior circulation AIS
within 24 hours of symptoms onset and with National
Institutes of Health Stroke Scale (NIHSS) score of ≥6.

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 Zaidat et al
CLINICAL PERSPECTIVE
TESLA (Thrombectomy for Emergent Salvage of
Large Anterior Circulation Ischemic Stroke) large
core infarct randomized clinical trial protocol and
design is unique; being the only large core infarct
randomized clinical trial that enrolled subjects
based on non-contrast head computed tomog-
raphy scan with Alberta Stroke Program Early CT
Score (ASPECTS) as low as 2 up to 24 hours from
symptoms onset.
Study Design
TESLA is an investigator-designed and -initiated, prag-
matic, phase III, prospective, randomized, open-label,
blinded end point, multicenter trial. Patients with large
infarcts will be assigned to either BMM alone (includ-
ing intravenous recombinant tissue-type plasminogen
activator [IV-rtPA]) or IAT added to BMM. Mechanical
thrombectomy will be performed with Food and Drug
Administration (FDA)-approved thrombectomy devices
in accordance with the instructions for use and under
FDA Investigational Device Exemption G190006. The
first patient was enrolled in July 2019 and the last
patient was enrolled in October 2022 with pending 90-
day and 1-year clinical follow-ups. Data are available
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at the cenral coordinator center for the study prinicipal
investigators (Yoo A, Zaidat OO).
Primary Trial End Points
1. Primary efficacy end point: comparing utility-
weighted 90-day mRS between BMM versus
IAT+BMM
2. Primary safety end point: comparing 90-day death
rate between BMM versus IAT+BMM
Prespecified Secondary End Points in
BMM and IAT+BMM Groups
• 1-year utility-weighted mRS
• 1-year mRS ordinal shift (mRS 5 and 6 combined)
• 1-year dichotomized mRS 0 to 2 outcome
• 1-year dichotomized mRS 0 to 3 outcome
• 90-day mRS ordinal shift (mRS 5 and 6 combined)
• 90-day dichotomized mRS 0 to 2 outcome
• 90-day dichotomized mRS 0 to 3 outcome
• NIHSS at 24 hours (16–36 hours) from randomization
• NIHSS at 6±1 days or discharge (whichever is earlier)
Stroke Vasc Interv Neurol. 2023;3:e000787. DOI: 10.1161/SVIN.122.000787
The TESLA Trial
• NIHSS of 0 to 2 or improvement of ≥8 points at
6±1 day or discharge (whichever is earlier)
• Length of hospital stay
• Discharge disposition
• Quality of life (EuroQol 5 Dimension 5 Level survey)
at 90 days
• Quality of life (EuroQol 5 Dimension 5 Level survey)
at 1 year
• 24-hour (16–36 hours) NCCT or diffusion-weighted
imaging ASPECTS
• 24-hour (16–36 hours) NCCT or diffusion-weighted
imaging infarct volume
• Procedural/time metrics: door to qualifying image,
door to needle (for IV-rtPA), door to puncture (for IAT),
image to puncture, puncture to modified Thrombol-
ysis in Cerebral Infarction (mTICI) 2b to 3, puncture
to end of the procedure (for subjects who achieve
final mTICI 0 to 2a, and defined as the final cerebral
angiogram on the affected hemisphere)
• Comparison of site, core lab, software ASPECTS
estimation (e-ASPECTS13–14; Brainomix, Oxford,
England, for sites that installed the software)
• Correlation of baseline CT perfusion results with 90-
day and 1-year outcomes
Prespecified Secondary End Points in IAT
Group
• Rate of first-pass effect to TICI 2c or 3 (ie, from first
treatment attempt)
• Rate of substantial reperfusion (mTICI 2b–3), excel-
lent reperfusion (TICI 2c–3), and complete reperfu-
sion (TICI 3), in the intra-arterial treatment arm
Prespecified Secondary Safety End Points
in BMM and IAT+BMM Groups
• Rate of symptomatic intracranial hemorrhage:
parenchymal hematoma type 2 with ≥4 points
NIHSS worsening (from immediate predeterio-
ration NIHSS) at 24 hours (16–36 hours) from
randomization
• Any neurological deterioration of ≥4 points on NIHSS
(from immediate predeterioration NIHSS) before day
6±1 or discharge (whichever is earlier) and unrelated
to symptomatic intracranial hemorrhage or seda-
tion (In addition to the routine 24-hour CT scan,
repeat neuroimaging is mandatory for any subse-
quent neurological deterioration at any time during
hospitalization.)
3
 Zaidat et al
• Rate of decompressive hemicraniectomy
• All serious adverse events, including serious adverse
device events, serious adverse procedural events,
and unanticipated serious adverse events
Prespecified Secondary Safety End Points
in IAT Group
• Emboli to new territory, in the intra-arterial treatment
arm
• Major vessel injury (perforation, dissection), in the
intraarterial treatment arm
Participating Centers and Center
Selection
Up to 65 centers in the United States and 15 cen-
ters in Europe may be invited to participate in the trial.
Center selection is determined by the following fac-
tors using site qualification questionnaires: AIS clini-
cal trial experience, endovascular case volume, stroke
center accreditation, operator experience with neu-
rointerventional procedures and mechanical thrombec-
tomy, and stroke triage imaging availability. Participat-
ing members of the neurointerventional team must per-
form at least 20 intracranial mechanical thrombectomy
cases annually. The neurointerventional credentialing
committee will review and approve the neurointerven-
tionalist on the basis of their training and experience
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via the neurointerventionalist-completed TESLA clini-
cal trial credentialing form. At least 1 investigator per
site should be trained and certified by the TENSION
(Efficacy and Safety of Thrombectomy in Stroke With
Extended Lesion and Extended Time Window () trial
web-based ASPECTS training module; only ASPECTS-
certified investigators may assess ASPECTS on the
baseline NCCT for trial eligibility. All sites must obtain
approval from the institutional review board.
Study Population
Inclusion and Exclusion Criteria
A complete screening form with inclusion and exclusion
criteria is provided in Table 1. Patients must be 18 to
85 years of age, presenting with AIS within 24 hours
of symptoms onset, with NIHSS score ≥6, and pre-
stroke mRS score 0 to 1. Eligible occlusions involve
the internal carotid artery terminus or middle cerebral
artery M1 segment. Patients must have evidence of
a large baseline infarct defined as NCCT ASPECTS
2 to 5. Key exclusion criteria are similar to IV-rtPA
criteria except for time window. Additionally, patients
cannot have imaging evidence of midline shift or her-
niation, intracranial hemorrhage, and mass effect with
Stroke Vasc Interv Neurol. 2023;3:e000787. DOI: 10.1161/SVIN.122.000787
The TESLA Trial
Table 1. TESLA Trial Inclusion and Exclusion Criteria.
Inclusion criteria
1 18–85 years of age
2 Presenting with symptoms consistent with an acute
ischemic stroke
3 Imaging evidence of an anterior circulation occlusion of
the ICA terminus or MCA M1 segment
4 NIHSS score ≥6 at the time of randomization
5 Ability to randomize within 24 hours of stroke onset
(stroke onset is defined as the time the patient was
last known to be at his/her neurologic baseline.
Wake-up strokes are eligible if they meet the above
time limits.)
6 Prestroke mRS score 0–1
7 Ability to obtain signed informed consent
8 If indicated, IV-rtPA should be administered as soon as
possible and no later than 3 hours from symptom
onset
Imaging inclusion criterion
Imaging evidence of moderate-large infarct defined as: NCCT ASPECTS
2–5
Exclusion
criteria
1 Women who are pregnant, or those of childbearing
potential with positive urine or serum beta human
chorionic gonadotropin test
2 Known severe allergy (more than a rash) to contrast
media uncontrolled by medications
3 Refractory hypertension (defined as persistent systolic
blood pressure >185 mm Hg or diastolic blood
pressure >110 mm Hg)
4 CT evidence of the following conditions:
Midline shift or herniation
Evidence of intracranial hemorrhage
Mass effect with effacement of the ventricles
5 CT angiography evidence suggestive of difficult
endovascular access per the treating interventionalist
6 Presence of cervical ICA complete occlusion (eg,
related to atherosclerotic disease or dissection)
7 Rapidly improving neurological status prior to
randomization to NIHSS <6
8 Bilateral strokes or multiple intracranial occlusions in
multiple territories
9 Intracranial tumors (except small meningiomas [≤3 cm])
10 Known hemorrhagic diathesis or coagulation factor
deficiency or on anticoagulant therapy with an
international normalized ratio of >3.0 or partial
thromboplastin time >3 times of normal
11 Baseline platelet count <30 000/μL
12 Life expectancy <1 year before stroke onset
13 Participation in another randomized clinical trial that
could confound the evaluation of the study
14 Any other condition (in the opinion of the site
investigator) that precludes an endovascular
procedure or poses a significant hazard to the patient
if an endovascular procedure was performed
ASPECTS indicates Alberta Stroke Program Early CT Score; ICA, internal
carotid artery; IV-rtPA, intravenous recombinant tissue-type plasminogen acti-
vator; MCA, middle cerebral artery; mRS, modified Rankin Scale; NCCT, non-
contrast computed tomography; NIHSS, National Institute of Health Stroke
Scale; and TESLA, Thrombectomy for Emergent Salvage of Large Anterior
Circulation Ischemic Stroke.
4
 Zaidat et al
effacement of the ventricles, cervical internal carotid
artery complete occlusion, and bilateral strokes.
STUDY PROCEDURES
Patient Screening and Enrollment
A signed informed consent form will be obtained for
those who meet inclusion criteria and none of the exclu-
sion criteria, and the patient will be randomized using
the RedCap Cloud web-based randomization mod-
ule. Patients with a signed informed consent form but
who are not randomized will undergo routine imag-
ing evaluation and receive standard therapy according
to local guidelines. The reason for no randomization
will be recorded. Patients with a signed informed con-
sent form who are randomized will be followed for the
entire 1-year study duration, regardless of whether they
received the assigned study intervention (ie, crossover).
Only patients who are randomized will be included in
the primary analysis. Up to 500 patients will be con-
sented during the screening process to identify 300 eli-
gible patients to undergo randomization. For patients
who undergo multiple imaging studies, the most recent
imaging study will be used for trial eligibility. Similarly,
for patients with multiple NIHSS scores, the one before
randomization will be used for trial eligibility (Figure, Trial
Consort Chart).
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Imaging Evaluation for Study Eligibility
NCCT ASPECTS Determination
Study eligibility will be based on the site investiga-
tor’s determination of ASPECTS on the baseline NCCT
scan. e-ASPECTS is an automated artificial intelligence
software that estimates the ASPECTS score in real
time.13–15 e-ASPECTS will be provided to the partici-
pating centers. Data output from the software will not
be used for patient selection and will be collected only
for secondary analyses. Feedback on ASPECTS reads
will be provided to the site investigators, when their
ASPECTS scores differ from the core lab by ≥2 points.
CT Angiography Evaluation for Vessel Occlusion
Baseline CT angiography of the head and neck ves-
sels must be performed to determine whether there
is an eligible large-vessel occlusion, the presence of
extracranial internal carotid artery complete occlusion,
or presence of occlusions in multiple vascular territories.
Additional Baseline Imaging
Additional neuroimaging studies (such as CT perfusion)
are not required but may be performed as standard of
Stroke Vasc Interv Neurol. 2023;3:e000787. DOI: 10.1161/SVIN.122.000787
The TESLA Trial
Figure. TESLA trial consortium chart: randomization will be
stratified for the following factors:
(1) age (≤70 or >70), 2) baseline ASPECTS (2–3 vs 4–5), 3) base-
line NIHSS (≤16 or >16), and 4) time from onset to imaging (0–6
vs >6–24 hours). ASPECTS indicates Alberta Stroke Program Early
CT Score; CTA, computed tomography angiography; ICA, internal
carotid artery; ICA-T, internal carotid artery terminus; MCA/M1, mid-
dle cerebral artery/M1 segment; NIHSS, National Institutes of Health
Stroke Scale; and TESLA, Thrombectomy for Emergent Salvage of
Large Anterior Circulation Ischemic Stroke.
care. However, they should not delay patient consent
and randomization.
Randomization and Stratification
Stratified randomization with permuted blocks will be
used. Randomization will be stratified by (1) age (≤70
or >70), (2) baseline ASPECTS (2–3 versus 4–5),
(3) baseline NIHSS (≤16 or >16), and (4) time from
onset to imaging (0–6 hours versus >6–24 hours).
Patients will be assigned (1:1 randomization) to either
the BMM arm or the IAT arm. Crossover from medi-
cal to endovascular therapy is not allowed; however,
crossover from endovascular to medical therapy is
allowed only if an endovascular contraindication arises
after randomization has occurred.
TREATMENT ARMS
IAT Arm
Sites will use local protocols for arterial access, seda-
tion, heparin infusion, monitoring, and the like. The
recommended time metrics for arterial puncture are
within 45 minutes of randomization, and within 60 min-
utes of qualifying imaging. IAT will be performed with
FDA-approved devices under Investigational Device
Exemption G190006. Residual middle cerebral artery
5
 Zaidat et al
second-order branch (M2) occlusions may be treated
using FDA-approved devices. Use of adjunctive tech-
niques such as balloon guide catheters or local
aspiration catheters will be at the discretion of the
site interventionalist. The use of adjuvant intra-arterial
thrombolytic medication is not approved by the FDA
and considered a protocol violation. Following IAT, it
is recommended that blood pressure be maintained
at 110 to 140/60 to 90 mmHg in subjects reperfused
to mTICI 2b to 3, and the same as the control sub-
jects, when no to minimal reperfusion (mTICI 0–2a) is
achieved.
BMM Arm
The BMM group will receive standard medical ther-
apy based on institutional standard protocols and path-
ways. The enrolling site’s post-IV-rtPA protocol will be
followed. Patients who do not receive IV-rtPA will be
treated with aspirin unless anticoagulation is indicated
(investigator’s preference). Dual antiplatelet therapy is
prohibited unless carotid stenting is performed. In sub-
jects who received IV-rtPA, blood pressure should be
managed according to the post–IV-rtPA protocol of
<185/105 mm Hg within the first 24 hours.
SCHEDULED ASSESSMENTS AND
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FOLLOW-UP VISITS
Timing of assessments is outlined in Table 2.
Blinding of Assessments and Statistical
Analysis for Safety Board Reporting
Assessment of outcome on NIHSS and mRS will be
performed by a certified rater blinded to the treat-
ment allocation and not involved in the procedure. Neu-
roimaging core lab evaluation will also be assessed in a
blinded manner, except for angiographic revasculariza-
tion grading. An unblinded independent statistician will
combine treatment allocation data with the clinical data
to report to the Data Safety Monitoring Board (DSMB).
A second blinded statistician will be part of the steering
committee.
Neurological Deterioration
Neurological deterioration is defined as ≥4-point wors-
ening of the immediate predeterioration NIHSS. NCCT
scan or magnetic resonance imaging (MRI) of the
brain should be obtained to adjudicate the underlying
deterioration cause.
Stroke Vasc Interv Neurol. 2023;3:e000787. DOI: 10.1161/SVIN.122.000787
The TESLA Trial
DATA SAFETY AND MONITORING
BOARD
An independent and unblinded DSMB was appointed
to oversee study safety (5 members, including 1 statis-
tician). An unblinded independent statistician will pro-
duce the reports on a regular basis, and at the request
of the DSMB along with the help of the coordinating
center. Another study statistician will remain blinded
throughout the study and serve on the steering commit-
tee. The DSMB will meet following each interim analysis
and on an as-needed basis but at a minimum of every
12 months.
TRIAL MONITORING
Trial site monitoring will be performed by the coordinat-
ing center in person or via virtual visits. The trial moni-
tors will review the source documents for accuracy and
for any protocol violation and will meet with the site
principal investigator following the monitoring visit for
reporting and whether a corrective action plan is nec-
essary with 100% confirmation of key study values (all
outcomes and adverse events). The coordinating cen-
ter will provide a semiannual report to the FDA on the
trial progress as per the FDA regulations.
STATISTICAL ANALYSIS
TESLA employs an intention-to-treat principle with an
adaptive enrichment design with a planned sample size
of 300 randomized patients (90% power). With 150
patients in each group, and an assumed odds ratio of
2.0 for improvement in 90-day mRS score with intra-
arterial treatment, the power is 90% with 1-sided alpha
of 0.025. The mRS distributions in the IAT and control
groups that are used for the sample-size calculation are
derived from the EVT and medical management groups
with ASPECTS 0 to 5 patients in the MR CLEAN RCT of
IAT and in the prospective MR CLEAN registry.1 Interim
analyses are to be performed with 150 and 225 sub-
jects to allow for enrichment and potential removal of
ASPECTS 2 to 3 subjects, as well as early stopping
for efficacy or futility, or continuation of the trial design
as is.
The primary analysis will be based on the Bayesian
posterior probability that, adjusted for ASPECTS score,
subjects in the IAT group have higher expected utility-
weighted mRS than subjects in the BMM-alone group.
A sensitivity analysis will be performed to examine the
results after subjects are allocated using core lab–
adjudicated ASPECTS. The secondary analysis will
determine whether there is modification of IAT effect
on the primary outcome by prespecified subgroups. All
6
 Zaidat et al The TESLA Trial

Table 2. TESLA Schedule of Assessments.

Procedure/ 24 hours Day 6 (±1 day) 30 days 90 days 1 year
Assessment/action Baseline postprocedure (16–36 hours) or DC# (±7 days) (±30 days) (±60 days)
Medical history X
Blood labs∗ X∗
Inclusion/exclusion X
Informed consent X
NCCT† X† X†
† †
CTA X X‡
† ‡
MRI /MRA X†
‡ ‡ ‡
CTP /MRP X X‡
Randomization X
Vital signs X X¶ X
NIHSS X X X
Modified Rankin scale X X X X X
Discharge disposition X
ASPECTS score X
Angiogram X¶
Procedure details X¶
§
ICH classification X§
¶
Adverse events X X X X X X
EQ-5D-5L|| X|| X||

Time points are from randomization. All assessments should be performed for both arms unless otherwise indicated. ASPECTS indicates Alberta Stroke Program
Early CT Score; CTA, computed tomography angiography; ‡ CTP, computed tomography perfusion; # DC, discharge; || EQ-5D-5L, EuroQol 5 Dimension 5 Level
survey; IAT, intraarterial thrombectomy; § ICH, intracranial hemorrhage; INR, international normalized ratio; ‡ MRA, magnetic resonance angiography; † MRI, magnetic
resonance imaging; ‡ MRP, magnetic resonance perfusion; NCCT, noncontrast computed tomography; NIHSS, National Institute of Health Stroke Scale; PTT, partial
thromboplastin time; and TESLA, Thrombectomy for Emergent Salvage of Large Anterior Circulation Ischemic Stroke.
∗
Platelets, INR (for patient on warfarin) and activated PTT (for patient on heparin or novel anticoagulants), and pregnancy test (if applicable).
†
NCCT/CTA must be performed at baseline according to a site’s standard of care. NCCT or MRI is mandatory at 24 hours and with any neurological serious
adverse event reporting.
¶
For IAT arm only.
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analyses will be performed on the intention-to-treat and ers and noninvasive imaging readers for NCCT, CT
per-protocol populations. angiography, and MRI assessments, led by Dr Charles
Majoie.

TRIAL ORGANIZATION AND FUNDING Clinical Event Monitoring Committee

TESLA is an industry-funded, investigator-initiated trial.
The overall principal investigators for the trial are Dr
Albert J. Yoo (Texas Stroke Institute, Dallas, TX) and
Dr Osama O. Zaidat (Mercy Health St. Vincent Medical
Center, Toledo, Ohio). The Central Coordinating Cen-
ter is Mercy Health St. Vincent Medical Center. The trial
is advised by an executive committee, steering com-
mittee, neurointerventionalist credentialing committee,
independent medical monitors, and an independent
DSMB. Data will be managed using an electronic data
capture system and housed at the coordinating center
(St. Vincent Medical Center). Statistical analyses will be
performed by an independent statistical group (Berry
Consultants).
Imaging Core Lab
The independent core lab includes 7 neuroradiologists
who are divided into 2 groups: angiographic read-
Two vascular and interventional neurologists formed
the independent clinical event monitoring committee to
review, in a timely manner, serious adverse events and
major protocol violations.
DISCUSSION
The IAT trials during the early time window of patients
with ASPECTS ≥6, and during the late time window of
estimated infarct size <70 mL with mismatch, demon-
strated more favorable outcomes in the IAT group over
the control group.1–5,9,10 This established IAT as the
standard of care in these small core populations.6 The
upcoming wave of clinical trials in European, North
American, and Asian Pacific populations are focused
on patients with AIS with LCI that were not addressed
by the above RCTs to expand the indication for IAT.

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 Zaidat et al
Importantly, these LCI trials use different imaging
modalities and definitions for large core infarction.
Because a large-core population identified using NCCT
is distinct from 1 defined using MRI or CT perfusion,
each LCI trial is unique and complementary to each
other. In a secondary analysis of the SAMURAI (stroke
acute management with urgent risk-factor assess-
ment and improvement) registry, 43% of patients with
diffusion-weighted imaging ASPECTS 3–5 had corre-
sponding NCCT ASPECTS 8–10 (ie, very small infarct
on NCCT).15 Similarly, because CT perfusion only pro-
vides a measure of collateral blood flow, it must forecast
tissue viability, thus explaining the well-described phe-
nomenon of ghost core (ie, CT perfusion–predicted
core that is spared from infarction).16
The first LCI clinical trial published was RESCUE-
Japan LIMIT (Recovery by Endovascular Salvage for
Cerebral Ultra-Acute Embolism–Japan Large Ischemic
Core Trial).17 The trial showed superior outcomes of
IAT versus BMM (31% versus 12.7%, respectively)
in patients with ASPECTS 3 to 5. However, the
LCI was defined mainly using MRI (87%), with 70%
enrolled within 6 hours of symptoms onset. Further-
more, dichotomized mRS 0 to 3 was chosen as the pri-
mary efficacy end point. Based on the SAMURAI data
cited above, these results do not apply to an ASPECTS
3 to 5 population determined using NCCT.
Unlike the other LCI trials, TESLA defines LCI exclu-
sively using NCCT, which is the predominant imaging
Downloaded from http://ahajournals.org by on December 1, 2023
modality for stroke evaluation in developed and low-
and middle-income countries. Furthermore, TESLA is
a pragmatic trial, meaning that patient allocation for
the primary analysis will be based on site ASPECTS
readings of the baseline NCCT. This will enhance
the generalizability of the trial results worldwide. Site
investigators were trained and certified for performing
ASPECTS within the trial. Agreement between the
site and core lab reads will be reported as part of the
statistical analysis plan.
In keeping with the pragmatic design, TESLA evalu-
ates a broader ASPECTS range than most of the other
LCI trials by including scores of 2. An adaptive enrich-
ment design was incorporated for potential removal of
ASPECTS 2 to 3 patients if they demonstrate futility.
TESLA also evaluates a broad time window up to
24 hours. The utility-weighted mRS was chosen as the
primary efficacy end point to convey patient-centered
outcomes, particularly at higher mRS scores. Finally, to
evaluate longer-term recovery, TESLA will report 1-year
clinical outcomes as secondary efficacy and safety end
points.
The heterogeneity in the triage imaging modalities
used within and between the LCI trials will render inter-
pretation of the results complex and clinical application
difficult. It will be important for all trials to report clini-
Stroke Vasc Interv Neurol. 2023;3:e000787. DOI: 10.1161/SVIN.122.000787
The TESLA Trial
cal results by imaging modality (ie, NCCT versus MRI
versus CT perfusion). An individual patient data, pooled
analysis will be critical to provide firmer conclusions
regarding treatment effects and potential ASPECTS
thresholds for each imaging modality used to triage
patients with LCI for IAT.
CONCLUSION
The ongoing LCI trials will provide critical evidence to
guide the selection of patients with anterior circulation
large-vessel occlusion for IAT. These trials are diverse in
their inclusion criteria, most importantly with regard to
the imaging modality used for determining the presence
of LCI. Together, they will enhance our understanding
of the influence of the imaging triage method on the
optimal infarct volume threshold for IAT. TESLA uses
solely NCCT imaging to evaluate the large ischemic
core population and will be highly generalizable.
ARTICLE INFORMATION
Received December 19, 2022; Accepted February 21, 2023
Affiliations
Neuroscience Institute, Bon Secours Mercy Health St. Vincent Hospital,
Toledo, OH (O.O.Z., M.S.P., H.S., K.B.); Medical University of South Carolina,
Charleston, IA (S.A.K.); UT Health McGovern Medical School, Houston, TX
(S.S.); University of Iowa Hospitals and Clinics, Iowa, IA (S.O.-G.); Rocke-
feller Neuroscience Institute, West Virginia University, Morgantown, WV (A.T.R.);
Baptist Healthy System, Lexington, KY (C.A.G.); University of Utah Medical
School, Salt Lake City, UT (R.G.); University of South Florida Medical School,
Tampa, FL (M.M.); Northwell Medical Center, Manhasset, NY (J.M.K.); Texas
Tech University Health Science Center at El Paso, El Paso, TX (A.M.); Well Star
Health, Atlanta, GA (R.G.); University of California San Francisco, San Fran-
cisco, CA (W.S.S.); Erasmus University Medical Center, The Randstad, Rotter-
dam, NA, Netherlands (D.W.D.); Nebraska Medical Center, Omaha, NE (D.G.);
Boston Medical Center, Boston, MA (T.N.N.); Altair Biostatistics, St. Louis
Park, MN (S.B.); Barrow Neurological Institute, Phoenix, AZ (A.P.J.); Univer-
sity of Tennessee, Memphis, TN (L.E.); Amsterdam University Medical Center,
Amsterdam, Netherlands (C.M.); Texas Stroke Institute, Dallas, TX (A.J.Y.)
Acknowledgments
The authors thank all TESLA site clinical research coordinators and site
investigators.
Sources of Funding
The TESLA Trial was conducted by an independent Clinical Trial Management
and Coordinating Center at St. Vincent Medical Center, Bon Secours Mercy
Health System, with multiindustry investigator research grants and support
(Stryker Neurovascular, Medtronic, Penumbra, Cerenovus, Genentech, and
Bon Secours Mercy Health Care System). The trial administration, design, con-
duct, data collection, monitoring, auditing, FDA communication/reporting, and
analysis were completely and solely performed by the CCC team at St. Vin-
cent Hospital, Toledo, Ohio, with no relation to any of the funding sources. The
investigational device exemption (IDE) approved application and responsibility
is under Dr Osama O. Zaidat.
Disclosures
Please see the completed disclosure forms by all authors.
8
 Zaidat et al
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