A REAl-life Study on Short-term Dual Antiplatelet Treatment in Patients With Ischemic Stroke or Transient Ischemic Attack
Conditions: Ischemic Stroke, TIA
Sponsor: University of L'Aquila

Page 1 of 13
 
 
A REAl-life study on short-term Dual Antiplatelet treatment in 
Patients with ischemic stroke or Transient ischemic attack 
(READAPT) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Protocol version 1.0 
24 December 2020 
 

Page 2 of 13
 
 
SCIENTIFIC COMMITTEE  
Name 
Affiliation 
Contact 
Stefano Ricci 
Department of Neurology and Stroke 
Unit, USL Umbria 1, Gubbio and Città di 
Castello Hospital, Perugia 
stefano.ricci@uslumbria1.it 
Simona Sacco 
Neuroscience section, Department of 
Applied Clinical Sciences and 
Biotechnology, University of L’Aquila, 
L’Aquila, Italy 
simona.sacco@univaq.it 
Tel. 0862433561 - 0863499734 
Danilo Toni 
Department of Human Neurosciences, 
‘Sapienza’ University, Rome, Italy 
danilo.toni@uniroma1.it 
Tel. 06 49979595 
STUDY MANAGER  
Name 
Affiliation 
Contact details 
Eleonora  
De Matteis 
Neuroscience section, Department of 
Applied Clinical Sciences and 
Biotechnology, University of L’Aquila, 
L’Aquila, Italy 
eleonora.dematteis@graduate.univaq.it 
 
STATISTICAL DATA MANAGER  
Name 
Affiliation 
Contact details 
Raffaele 
Ornello 
Neuroscience section, Department of 
Applied Clinical Sciences and 
Biotechnology, University of L’Aquila, 
L’Aquila, Italy 
raffaele.ornello@gmail.com 
 
 
 

Page 3 of 13
 
 
PROTOCOL SYNOPSIS 
 
Title: 
A REAl-life study on short-term Dual Antiplatelet treatment in 
Patients with ischemic stroke or Transient ischemic attack 
(READAPT) 
 
Objectives: 
Aim of the present study is to evaluate the benefits and harms of 
dual antiplatelet treatment in patients fulfilling different possible 
definitions of minor or moderate acute ischemic stroke or high risk 
transient ischemic attack (TIA) and to evaluate risk and benefits in 
subgroups of patients which were not addressed in the randomized 
clinical trials. 
 
Study design and 
setting: 
Observational multicenter Italian study including centers affiliated 
to the Italian Stroke Organization. 
 
Population: 
Patients with ischemic stroke or transient ischemic attack aged at 
least 18 years. 
 
Key inclusion 
criteria:  
Consecutive patients with mild or moderate acute ischemic stroke 
or high-risk TIA treated with a short course of dual antiplatelet 
treatment. 
 
Key exclusion 
criterion: 
Patients with acute ischemic stroke or TIA who receive dual 
antiplatelet treatment because of vascular stenting, acute coronary 
syndrome, or any other indication not related to the acute 
cerebrovascular event. 
 
End points: 
The main considered endpoints will be occurrence of total stroke, 
ischemic stroke, TIA, death, disability, intracerebral bleeding, 
systemic bleeding. Treatment adherence will also be evaluated. 
 
Recruitment period: 
Planned study duration is of 2 years (24 months). 
 
Follow-up: 
Patients will be followed-up for 90 days with in-person visits or 
telephone calls. 
 
Statistical analyses: 
We will evaluate occurrence of outcome events in the overall 
cohort and will perform sensitivity analyses by groups which are 
considered relevant according to the clinical perspective (i.e. type 
of event, time to dual antiplatelet treatment [DAPT], type of 
DAPT, DAPT duration, clinical severity of the index event and its 
acute treatment).  
 

Page 4 of 13
 
 
STUDY PROTOCOL 
 
1. BACKGROUND INFORMATION AND SCIENTIFIC RATIONALE 
Recent data from randomized controlled trials (RCTs) indicate that short-term dual antiplatelet 
therapy (DAPT) with aspirin and clopidogrel or aspirin and ticagrelor for 21-30 days may 
provide benefits over treatment with a single antiplatelet agent in patients with mild or moderate 
ischemic stroke or high-risk transient ischemic attack (TIA)1-4. Also a recent Cochrane 
metanalysis including data from 15 RCTs confirmed the benefit of DAPT in reducing stroke 
recurrence, which outweigh the harm of the treatment 5. 
Three RCTs (CHANCE, FASTER, POINT) tested the combination of aspirin and clopidogrel 
versus aspirin and placebo (Table).1-3 Only patients with mild ischemic stroke and high-risk 
TIA were included in those trials. Minor ischemic stroke was defined as a National Institutes 
of Health Stroke Scale (NIHSS) score of 3 or less in the POINT, CHANCE and FASTER trials. 
High-risk TIA was defined as an ABCD2 score of 4 or more in CHANCE and POINT trials,1,3 
while in the FASTER trial, TIA patients needed to have either weakness or speech disturbance 
as part of the symptom complex with a duration of at least 5 minutes to qualify for inclusion in 
the study.2  More recently, one RCT (THALES) tested aspirin and ticagrelor versus aspirin and 
placebo in people with mild or moderate ischemic stroke, i.e. NIHSS score of 5 or less, or high-
risk TIA defined as ABCD2 score of 6 or more 4 (Table 1). 
It is not established if findings of RCTs can be replicated in real-life settings. In fact, to be 
included in the trials, patients had to meet strict inclusion and exclusion criteria which are not 
always fulfilled by patients, who in real-life receive DAPT. Patients with low-risk TIA or only 
possible TIA were not included in any of the identified RCTs. Moreover, definition of mild 
ischemic stroke was inconsistent among the RCTs, and patients eligible for revascularization 
procedures were excluded, as well as patients with events attributed to procedures such as 
carotid endarterectomy.  

Page 5 of 13
 
 
2. STUDY OBJECTIVES 
The aim of the present study is to evaluate the benefits and harms of dual antiplatelet treatment 
in patients with mild-to-moderate acute ischemic stroke or high-risk TIA in a real-life setting. 
The study will aim to evaluate if findings of the RCTs can be replicated and to explore subgroup 
of patients who were not included in the trials for whom information was unclear. Additionally, 
this study will evaluate adherence to the prescribed treatment in a real-life setting. 
 
3. METHODS 
3.1 Study design 
The study is a prospective observational multicenter Italian study.  
3.2 Study setting 
The study will involve patients from 126 Neurology departments and Stroke Units located in 
Italy and affiliated to the Italian Stroke Organization (ISO).   
All Centers affiliated to the ISO were contacted. The list of participating Centers is reported in 
Appendix 1. 
The University of L’Aquila and the Neurology department of SS Filippo e Nicola hospital in 
Avezzano will have the role of coordinating center.  
Further centers could join the project depending on study needs. Participation of any new center 
must be approved by the Institutional Review Board (IRB) of the coordinating center. A 
communication to the IRB of all the participating centers will be also sent.   
3.3 Study population 
The study will include consecutive patients referring to the selected Centers who fulfill the 
criteria to participate in the study.  
3.4 Inclusion criteria 
The study will include all subjects who meet all the following inclusion criteria: 
1. Patients with mild or moderate non-cardioembolic ischemic stroke or high-risk TIA 
treated with a short course of DAPT (usually 21-30 days but up to 90-day at the 
physician’s discretion) for the acute event;  
2. Male or female aged at least 18 years; 
3. Providing signed and dated informed consent form; 
4. Willing to comply with all study procedures and to be available for the duration of the 
study. 
As one the major study aim is to evaluate DAPT in the real-life setting, the protocol will not 
adopt predefined criteria to define mild-to-moderate ischemic stroke or high-risk TIA. Data on 
ischemic stroke severity as defined by the NIHSS and on TIA-related stroke risk as defined by 
the ABCD2 score will be collected to stratify patients and perform subgroup analyses.  
For the same reason we did not adopt any pre-defined inclusion criteria for initiation of DAPT 
after the acute event as one of the objectives of the study is to describe timing from acute event 
to initiation of the acute treatment and provide data for efficacy and safety stratified for 
subgroups.  

Page 6 of 13
 
 
Moreover, we will not adopt stringent criteria referring to duration of DAPT but we will try to 
maximize adherence to guidelines or treatment paradigm of the RCTs.1-6 Conventional duration 
of DAPT is from 21 to 90 days.   
We also recognize that at the time of starting the study, ticagrelor will be probably not approved 
in Italy for stroke prevention and thus patients treated with ticagrelor will not be included in the 
study. Anyhow, the protocol was drafted to allow the inclusion of patients treated with 
ticagrelor if the drug will receive the approval before study completion.  
3.5 Exclusion criteria 
Subjects presenting with the following characteristics will not be included in the study: 
1. Patients receiving DAPTs after endovascular procedures with stenting; 
2. Patients who are randomized in any interventional RCTs on stroke prevention; 
3. Presence of any condition which at the physician judgement may preclude reliability of 
the collected information; 
3.6 Variables of interest 
The study will collect information on patients’ characteristics, vascular risk factors, pre-event 
treatment, stroke severity (as measured by the NIHSS), ABCD2 score, carotid or intracranial 
stenosis, pre- and post-event disability (as measured by the modified Rankin Scale [mRS] 
score), time from symptom onset to initiation of DAPT, type of DAPT with loading and daily 
dosage, duration of DAPT, neuroimaging characteristics, findings at examinations to ascertain 
the cause of the event, treatment in the acute phase (thrombolysis/thrombectomy), treatment at 
discharge, outcome and adverse events occurring during the follow-up. 
A detailed list of the variables of interest which will be collected for the present study is reported 
in the Appendix 2 which displays the baseline case report form (CRF) of the study. 
3.7 Recruitment 
Each participating center will be requested to include in the study all consecutive patients 
(hospitalized or non-hospitalized) who will meet inclusion criteria for the study. We anticipate 
that the study will mostly include patients who will be hospitalized for the index event. 
Inclusion of non-hospitalized patients managed in the emergency department of dedicated TIA 
outpatient clinics will be allowed and encouraged.  
3.8 Study duration 
Recruitment period will last two years from the approval of the Institutional Review Board of 
the coordinating center. Follow-up will last for 90 days for each included patient.  
3.9 Follow-up 
A single follow-up visit will be scheduled for each patient at 90±5 days from symptom onset. 
Follow-up visits may be in-person or via a telephone call depending on the center practice. 
Scheduled telephone calls will be performed by trained research staff or health care staff at the 
local clinic. Consent to be contacted for a telephone interview is included in the consent form 
subscribed before inclusion in the study.  
At the follow-up visit the local PI or the co-investigators will fill-in the control visit data 
collection form. The detailed list of variables of interest for the follow-up visit can be found in 
the follow-up CRF shown in Appendix 3.  
3.10 Study Outcomes 

Page 7 of 13
 
 
The primary efficacy outcome will be a composite of new stroke events (ischemic or 
hemorrhagic) or death at 90 days.  
The primary safety outcome will be any moderate-to-severe bleeding event. 
Key secondary efficacy outcomes will include ischemic stroke, intracerebral hemorrhage, 
subarachnoid hemorrhage, myocardial infarction, vascular death, and any hospitalization. Key 
secondary outcome will also include disability as measured by the mRS and adherence to DAPT 
and other stroke preventive agents. 
Secondary safety outcome will include minor bleeding events.  
Outcomes will be adjudicated at each center by the local Principal Investigator (PI). 
Adjudication of outcomes will be based on review of medical charts.  
3.11 Study procedures 
The study is observational and no change in diagnostic and treatments procedures will be made. 
Patients will be treated according to the doctor’s decisions and in line with the available 
guidelines and current good clinical practice. 
Data will be collected locally by physicians and other health care professionals involved in 
patient care. At each visit, a paper copy of collected data for each included patient will have to 
be stored at local Centers. The paper copy will contain demographic information, along with a 
patient ID that will be unique for each patient and will be created upon insertion of the data in 
the e-CRF. The record ID of the patient will be requested in the e-CRF at follow-up visits. Only 
local Centers will know the identity of included patients. In the e-CRF patients will be identified 
by their ID.  
 
4. STATISTICAL ANALYSIS 
Statistical analyses will be performed by the statistical data manager under the advice of the 
SC.  
All analyses will be performed according to the intention-to-treat principle in all patients died 
within 90 days or completing the 90-day follow-up. 
Descriptive statistics will be used to report baseline information.  
We will analyze the time from event to the first occurrence of primary and secondary outcome 
events with the use of a Cox proportional hazards model. We will use two statistical models; 
Model 1 will be unadjusted, while Model 2 will be adjusted for age, arterial hypertension, 
diabetes mellitus, cigarette smoking, and baseline mRS score. P values for interaction will be 
calculated according to the following subgroups: type of event (ischemic stroke vs TIA), time 
to DAPT (≤24 hours vs >24 hours from symptom onset), type of DAPT (aspirin+clopidogrel 
vs aspirin+ticagrelor), DAPT duration (≤21 vs >21 days and ≤30 vs >30 days), NIHSS score at 
onset (≤3 vs >3 and ≤5 vs >5), revascularization procedure (i.v. thrombolysis and/or mechanical 
thrombectomy vs no interventions). Hazard ratios with 95% confidence intervals will be 
reported. Should multiple events of the same type occur, the time to the first event will be used 
in the model. Data from patients who had no events during the study will be censored at the 
time of study termination or death.  
Assuming a 95% confidence interval, we estimate that a sample size of 347 subjects would be 
required to detect a 6% proportion of primary outcome occurrence with a two-sided 5% margin 
of error. The 6% proportion was taken from the THALES trial.4 

Page 8 of 13
 
 
Tests will be two-sided, and a P value of 0.05 will be considered to indicate statistical 
significance. All statistical analyses will be performed with the use of SPSS software. 
 
5. ETHICS 
5.1 Ethical approval 
The study will be firstly approved by the Institutional Review Board of the coordinating center 
and then submitted to local Ethic Committee (EC) or IRB of all the participating centers.  
All study procedures will start after EC or IRB approval. Additionally, any other necessary 
approvals required by sites will be obtained prior to initiation of the study at each site.  
Each center will be in charge of storing its own Ethical Documentation.  
5.2 Patient Information Sheet and patient informed consent 
The patient information sheet and informed consent have to be approved at each study site. A 
master patient information sheet and informed consent form will be provided to all participating 
centers in Italian language. Each Center will be in charge adapt to local procedures.  
The research staff will seek consent from any eligible patient for enrolment into the study. At 
the time of the first visit an explanation of the study, a patient information sheet, and an 
informed consent form will be provided. Adult patients able to understand the study information 
must personally sign the informed consent form before being included in the study. In the 
presence of aphasia or any other condition impairing the ability to provide an informed consent, 
the consent will be requested to the patients’ legal representatives or to a proxy.  
Signed informed consent forms will be stored locally upon the responsibility of the local PI, 
who will be responsible for providing them upon request of authorized auditors and authorities.  
5.3 Privacy of data 
The CRF includes anonymized data which will not allow to identify or contact the patient. Only 
the recruiting center will be aware of the patient identity.  
5.4 Withdrawal from participation 
Included patients may request to have their information deleted from the study at any time. 
Included patients do not have to disclose their reasons for withdrawal of consent. The local PI 
will inform the study manager and include a record of end of study participation. 
5.5 Modifications of the study protocol  
Any modification of the registry protocol, including substantial changes in collected 
information, will require a formal amendment to the protocol. 
5.6 Risk analysis 
The study is observational and does not change the usual clinical practice. The study does not 
put patients at any specific risk related to study procedures.  
5.7 Premature termination of the study 
This study may be suspended or prematurely terminated for predictable and unpredictable 
causes. Premature termination of the study can be decided by the SC. Circumstances that may 
warrant termination include, but are not limited to: 
• 
Insufficient adherence to protocol requirements. 
• 
Data that are not sufficiently complete and/or evaluable.  

Page 9 of 13
 
 
• 
Determination of futility. 
If the study is prematurely terminated or suspended, the local PI will promptly inform the EC 
and will provide the reason(s) for suspension or termination. 
 
6. DATA SECURITY, MANAGEMENT, QUALITY, AND PROPERTY 
6.1 Data collection and storage 
Data will be collected using the REDcap software. Detailed information on security of the 
system can be found at https://projectredcap.org. 
The local PI or the co-investigators will be able to upload patient data through a single form 
specifically created for the study, which will include a user-friendly drop-down menu.  
Anonymized data are stored on a secured server upon the responsibility of University of 
L’Aquila. The data are automatically backed-up once a week.  
Data will not be shared with unauthorized persons. 
6.2 Quality management 
The database incorporates automated inputs to prevent errors.  
Plausibility of the entered data will be checked. After data from each CRF is entered into the 
registry, data will be manually verified by the study manager and the statistical data manger 
and data queries will be resolved with the study site. Cases with missing data or unresolved 
queries will be rejected to ensure only the highest quality data are retained in the registry.  
Data from centers not ensuring consecutive recruitment of patients or adequate follow-up will 
not be included in the final data base.  
6.3 Property of data 
Aggregated data belong to the ISO. 
6.4 Governance of data 
Local PIs will have unrestricted access to the data of their patients. The study SC, the study 
manager, and the statistical data manager will have access to the whole database.  
Data from the study can be shared upon reasonable request and for scientific purposes only after 
the approval of all the members of the SC.  
 
7. STUDY MANAGEMENT 
The study has a SC who is responsible of the study design and the whole project. The study will 
have a study manager and a statistical data manager.  
The study manager will create and manage the electronic CRF. Upon the course of the study, 
the study manager will check the quality of the data entered into the database and contact centers 
sending queries to solve possible problems. The study manager will issue a periodic newsletter 
for study participants reporting progresses of the study and will provide reminds to participating 
centers for follow-up visits.  
The statistical data manager will be in charge of exporting data from the server and of providing 
preliminary reports. The statistical data manager will perform all the statistical analyses under 
the guide of the SC. 

Page 10 of 13
 
 
7.1 Local study staff 
Each center will be led by a local PI. The local PI will select the local co-investigators. 
Participation of the local co-investigators has to be approved by the local EC or IRB. The local 
PI will inform the SC and the study manager of the personnel involved in the study and of any 
change that may occur over time. The study manager will store a list of all the investigators 
contributing to the study and will update this list as needed.  
7.2 Staff training 
The study manager will perform a specific training upon request from the involved clinical site 
before starting enrollment. The training will be done remotely. During the training all the study 
procedures will be explained to the local PI and coinvestigators and CRF will be explained in 
detail.  
 
8. FUNDINGS AND STUDY COSTS 
This is a no-profit study. Local PIs and co-investigators will not have to pay any fee to 
participate in the project and will not be compensated. All procedures will be covered through 
the standard of care insurance or public health system covering the patients’ medical care. 
Participants will receive no payment for participation in this study.  
The present study may receive funding by application to research agencies or private parties. 
Any funding shall be approved by the SC and managed through the ISO office or University 
Departments.  
 
9. DATA SHARING AND PUBLICATIONS 
9.1 Scientific publications 
Data from this study will lead to aggregated reports which will be published in Scientific 
Journals and presented at national and international conferences.  
The publication plan is decided by the SC. Proposals of publications can also be received by 
the local PIs. Any proposal of data analysis and publication derived from this study has to be 
approved by the SC. Each proposal must report a clear aim and a detailed statistical analysis 
plan.  
For each approved publication the SC will designate one leading (first author of the paper) and 
one guarantee author (last author of the paper). The leading author will be in charge of drafting 
the manuscript, of organizing the statistical analyses, and coordinating the study group. The 
guarantee author will support the leading author in writing the manuscript, in revising the text 
and in all the procedures which will be necessary to finalize the project.  
9.2 Authorship 
To meet authorship criteria, local investigators shall include all consecutive patients meeting 
study criteria and provide the complete follow-up data for each included and consenting patient. 
Investigators from centers with poor data quality which will not be included in the analysis will 
not meet authorship criteria.   
Maximal effort will be done to include the local investigators of the participating centers as 
study contributors in all the publications derived from the study. When Journals will put a limit 
in the number of contributing authors, selection for authorship will be done by giving priority 
to one investigator per center as first criterion and to the centers including higher number of 
patients as second criterion. In any case, all local PIs and co-investigators will receive group 

Page 11 of 13
 
 
authorship in every publication derived from this study; in this case “on behalf of the Italian 
Stroke Organization” will be used as the preferred terminology to assign group authorship.  
9.3 Costs of publications 
The SC may ask to the ISO to cover the publication fees for articles published in open-access 
journals. Other funding to cover publication costs can be searched. Any funding should be 
approved by the study SC. Funding can be used also to cover possible costs for medical writing 
of statistical analyses. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Avezzano, 24 December 2020 
Professor Simona Sacco 
 
 
 

Page 12 of 13
 
 
REFERENCES 
 
1. Wang Y, Wang Y, Zhao X, et al. CHANCE Investigators. Clopidogrel with aspirin in acute 
minor stroke or transient ischemic attack. N Engl J Med 2013;369:11-9.  
2. Kennedy J, Hill MD, Ryckborst KJ, Eliasziw M, Demchuk AM, Buchan AM. FASTER 
Investigators. Fast assessment of stroke and transient ischaemic attack to prevent early 
recurrence (FASTER): a randomised controlled pilot trial. Lancet Neurol 2007;6:961-9.  
3. Johnston SC, Easton JD, Farrant M, et al. Clinical Research Collaboration, Neurological 
Emergencies Treatment Trials Network, and the POINT Investigators. Clopidogrel and aspirin 
in acute ischemic stroke and high-risk TIA. N Engl J Med 2018;379:215-25. 
4. Johnson SC, Amarenco P, Denison H, et al. Ticagrelor and Aspirin or Aspirin Alone in Acute 
Ischemic Stroke or TIA. NEJM 2020;383:207-217. 
5. Naqvi  IA, Kamal  AK, Rehman  H. Multiple versus fewer antiplatelet agents for preventing 
early recurrence after ischaemic stroke or transient ischaemic attack. Cochrane Database of 
Systematic 
Reviews 
2020, 
Issue 
8. 
Art. 
No.: 
CD009716. 
DOI: 
10.1002/14651858.CD009716.pub2. Accessed 13 December 2020 
6. Powers WJ, Rabinstein AA, Ackerson T, et al. Guidelines for the Early Management of 
Patients With Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early 
Management of Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the 
American Heart Association/American Stroke Association. Stroke. 2019;50:e344-e418 
 
 
 
 

Page 13 of 13 
 
Table 1. Randomized Clinical Trials on short-term Dual Antiplatelets Treatments in patients with ischemic stroke or Transient Ischemic attack. 
Abbreviations in the table: modified Rankin scale (mRS); National Institutes of Health Stroke Scale (NIHSS); Transient ischemic attack (TIA); Non-steroidal antinflammatory 
drugs (NSAIDs)  
Trial 
Age range 
Time-window 
Population 
Main exclusion criteria 
Treatment regimen 
Dual antiplatelet 
treatment duration 
CHANCE 1 
40 years 
24 h 
-Ischemic stroke with 
NIHSS  3  
- High-risk TIA (ABCD2 
4) 
TIA with isolated sensory symptoms (i.e., 
numbness), isolated visual changes, or isolated 
dizziness or vertigo; thrombolysis for the event; 
pre-morbid mRS≥2; anticipated use of NSAIDs; 
use of anticoagulants  within 10 days before 
randomization; planned or probable 
revascularization; TIA or minor stroke caused by 
procedure 
Aspirin: loading dose 75-
300 mg followed by 75 
mg daily 
Clopidogrel: loading 
dose of 300 mg followed 
by 75 mg daily aspirin 
on days 22 through 90. 
21 days 
FASTER2 
40 years 
24 h (efforts to 
have a relevant 
proportion of 
patients starting 
treatment  12 
h) 
-Ischemic stroke with 
NIHSS  3  
-TIA (defined by weakness 
or speech disturbance, 
dysarthria or dysphasia, for 
greater than 5 min) 
Acute coronary syndrome, pre-morbid mRS≥3, 
event secondary to a procedure (ie, carotid 
stenting) 
Aspirin: loading dose of 
162 mg (if patients were 
naïve to aspirin) 
followed by 81 mg daily 
Clopidogrel: 300 mg 
loading dose followed by 
75 mg daily 
90 days 
POINT3 
18 years 
12 h 
-Ischemic stroke with 
NIHSS  3  
-High-risk TIA (ABCD2 
4) 
Candidates for thrombolysis, endovascular 
therapy, or endarterectomy; use of NSAIDs for 
more than 7 days during the trial period 
Aspirin: 50- 325 mg 
daily 
Clopidogrel: 600-mg 
loading dose followed by 
75 mg daily. 
90 days 
THALES4 
40 years 
24 h within 
onset or from 
the last time 
seen well 
-Ischemic stroke with 
NIHSS 5  
-TIA with ABCD26 or 
symptomatic intracranial 
or extracranial arterial 
stenosis (≥50% narrowing 
in the diameter of the 
lumen of an artery that 
could account for the TIA) 
Intravenous or intraarterial thrombolysis or 
mechanical thrombectomy; history of atrial 
fibrillation or ventricular aneurysm or a suspicion 
of a cardioembolic cause of the TIA or stroke, 
planned carotid endarterectomy; major surgery 
within 30 days before randomization 
Aspirin: loading dose of 
300- 325 mg followed by 
75-100 mg daily 
Ticagrelor: 180 mg 
loading dose followed by 
90 mg daily  
30 days 

Page 1 of 8 
Appendix 1: Center List 
 
Center 
City (district) 
Principal investigator 
Contact 
Unità di trattamento neurovascolare, 
Azienda Ospedaliero Universitaria  
Policlinico Umberto I 
Roma (RM) 
Danilo Toni 
danilo.toni@uniroma1.it 
Neurologia e Stroke Unit, Ospedale SS 
Filippo e Nicola 
Avezzano (AQ) 
Simona Sacco 
Simona.sacco@univaq.it 
Neurologia e Stroke Unit, Ospedale 
San Salvatore 
L’Aquila (AQ) 
Francesca Pistoia 
 
francesca.pistoia@univaq.it 
 
Neurologia, Ospedale SS Annunziata 
Sulmona (AQ) 
Mario Di Napoli 
mariodinapoli@katamail.com 
Stroke Unit, Policlinico di Bari 
Ospedale Giovanni XXIII 
Bari (BA) 
Marco Petruzzellis 
mpetruz@hotmail.com 
Neurologia e Stroke Unit, Arzignano 
Azienda ULSS 8 Berica 
Vicenza (VI) 
Michela Marcon 
michela.marcon@aulss8.veneto.it 
Neurologia, Ente Ospedali Galliera 
Genova  
Genova (GE) 
Massimo Del Sette 
massimo.del.sette@galliera.it 
Clinica Neurologica, Ospedale San 
Gerardo e Università Milano Bicocca 
Monza (MB) 
Carlo Ferrarese 
carlo.ferrarese@unimib.it 
Neurologia, Azienda Ospedaliera 
Universitaria Integrata di Verona 
Verona (VR) 
Manuel Cappellari 
manuel.cappellari@aovr.veneto.it 
Neurologia con Centro Ictus, Ospedale 
S.Corona 
Pietra Ligure (SV) 
Tiziana Tassinari 
t.tassinari@asl2.liguria.it 
Neurologia, Ospedale Villa Sofia 
 
Palermo (PA) 
Valeria Terruso 
vterruso@libero.it 
Neurologia, Azienda Ospedaliero-
Universitario di Parma 
Parma (PR) 
Umberto Scoditti 
uscoditti@ao.pr.it 
Neurologia e Stroke Unit, Presidio 
Ospedaliero "Di Venere"  
Bari (BA) 
Giuseppe Rinaldi 
neurologia.divenere@asl.bari.it 
Stroke Unit, ASST Vimercate 
 
Vimercate (MB) 
Paola Bazzi 
paola.bazzi@asst-vimercate.it 
Neurologia, Ospedale Santa Croce 
 
Cuneo (CN) 
Piero Meineri 
pieromeineri@hotmail.com 
Stroke Unit, Ospedale A. Perrino  
 
Brindisi (BR) 
Salvatore Laspada 
salvatore.laspada@alice.it 
Stroke Unit, Istituto Ospedaliero 
Fondazione Poliambulanza 
Brescia (BS) 
Paolo Invernizzi 
Paolo.Invernizzi@poliambulanza.it  
Neurologia e Stroke Unit, Ospedale 
Cardarelli 
Napoli (NA) 
Valentino Manzo 
valentino.manzo@aocardarelli.it  

Page 2 of 8 
Appendix 1: Center List 
 
Neurologia, Ospedale Maria Paternò 
Arezzo 
Ragusa (RG) 
Emanuele Caggia 
manucaggia@gmail.com 
Clinica Neurologica, Azienda 
Ospedaliera-Universitaria Giuliano 
Isontina 
Trieste (TS) 
Marcello Naccarato 
marcello.naccarato@hotmail.com 
Neurologia, Ospedale San Jacopo 
  
Pistoia (PT) 
Gino Volpi 
gino.volpi@uslcentro.toscana.it 
Neurologia, ASST Lariana, Ospedale 
Sant’Anna 
San Fermo della Battaglia (CO) 
Giampiero Grampa 
giampiero.grampa@asst-lariana.it 
Stroke Unit, ASST Franciacorta 
 
Brescia (BS) 
Vincenzo Sidoti 
vincenzo.sidoti@asst-franciacorta.it 
Neurologia d’urgenza e Stroke Unit, 
Presidio Ospedaliero di Pescara  
Pescara (PE) 
Francesco Di Blasio 
francesco.diblasio@ausl.pe.it 
Neurologia, Ospedale di Legnago  
 
Legnago (VR) 
Michelangelo Turazzini 
mturazzini@katamail.com 
Neurologia, ASST Melegnano e della 
Martesana 
Melegnano (MI) 
Carla Zanferrari 
carla.zanferrari@asst-melegnano-
martesana.it 
Stroke Unit, Ospedale Rovigo, ULSS 18 
 
Rovigo (RO) 
Monia Russo 
monia.russo@aulss5.veneto.it 
Neurologia e Stroke Unit, Arcispedale 
Santa Maria Nuova 
Reggio Emilia (RE) 
Marialuisa Zedde 
marialuisa.Zedde@ausl.re.it 
Neurologia, Ospedale Civile SS. 
Annunziata 
Savigliano (CN) 
Roberta Bongioanni 
robibongio@gmail.com 
Stroke Unit, Azienda ospedaliera 
universitaria Senese 
Siena (SI) 
Rossana Tassi 
rossanatassi60@gmail.com 
Neurologia, Presidio ospedaliero 
Umberto I Nocera Inferiore 
Salerno (SA) 
Teresa Cuomo 
dottoressacuomo@gmail.com 
Neurologia, ASST Papa Giovanni XXIII 
 
Cremona (CR) 
Bruno Censori  
bcensori@hpg23.it 
Malattie Cerebrovascolari e Stroke 
Unit IRCCS Istituto Neurologico  
Mondino 
Pavia (PV) 
Anna Cavallini 
anna.cavallini@mondino.it 
Neurologia, ASST Merate 
Merate (LC) 
Andrea Salmaggi 
a.salmaggi@asst-lecco.it 
Neurologia, Azienda ospedaliera e 
universitaria Pisana 
Pisa (PI) 
Michelangelo Mancuso 
mancusomichelangelo@gmail.com 
Neurologia, Ospedale San Giovanni di 
Dio 
Firenze (FI) 
Alberto Fortini 
alberto.fortini@uslcentro.toscana.it 

Page 3 of 8 
Appendix 1: Center List 
 
Stroke Unit, AOUUD Santa Maria della 
Misericordia  
Perugia (PG) 
Maurizio Paciaroni 
maurizio.paciaroni@unipg.it 
Clinica Neurologica Stroke Unit, 
Ospedale SS Annunziata 
Chieti (CH) 
Maria Vittoria De Angelis 
mavidea@yahoo.it 
Neurologia e Stroke Unit e 
Neurofisiopatologia, AOUP Paolo 
Giaccone  
Palermo (PA) 
Paolo Aridon 
paolo.aridon@unipa.it 
Neurologia e Stroke Unit, Azienda 
Ospedaliero Universitaria Maggiore 
della Carità 
Novara (NO) 
Roberto Tarletti 
robertotarletti@yahoo.it 
Neurologia e Stroke Unit, ASUR 
Marche AV2 Jesi 
Jesi (AN) 
Emanuele Medici 
emanuelemedici@yahoo.it 
Neurologia, Ospedale Vito Fazi 
 
Lecce (LE) 
Leonardo Barbarini 
clasi33@libero.it 
Stroke Unit, Azienda Ospedaliero 
Universitaria Sant'Andrea  
Roma (RM) 
Mario Beccia 
beccia.mario@gmail.com 
Neurologia e Stroke Unit, Ospedale 
Guzzardi di Vittoria 
Vittoria (RG) 
Antonello Giordano 
antonello.giordano@asp.rg.it  
Neuro Vascolare, Ospedale Maria 
Vittoria  
Torino (T0) 
Fabio Melis 
fabio.melis@aslcittaditorino.it 
Neurologia e Stroke Unit Ospedale 
San Bortolo  
Vicenza (VI) 
Francesco Perini 
francesco.perini@aulss8.veneto.it 
Stroke Unit, Azienda Ospedaliera San 
Camillo 
Roma (RM) 
Sabrina Anticoli 
santicoli@scamilloforlanini.rm.it 
Stroke Unit, Azienda Ospedaliera "San 
Carlo" di Potenza  
Potenza (PZ) 
Antonio Matera 
matera.a@tiscali.it 
Neurologia e Stroke Unit, ASST 
Settelaghi 
Varese (VA) 
Federico Carimati 
federico.carimati@asst-settelaghi.it 
Neurologia, ASUR Area Vasta 4  (ex 
ZT11)  
Fermo (FM) 
Patrizio Cardinali 
patrizio.cardinali@sanita.marche.it 
Stroke Unit, Azienda Ospedaliera 
Universitaria Careggi 
Firenze (FI) 
Patrizia Nencini 
nencinip@aou-careggi.toscana.it 
Neurologia Ospedale Sant’Andrea, 
Azienda Sanitaria Locale n. 5 
“Spezzino” La Spezia 
La Spezia (SP) 
Elisa Giorli 
Elisa.giorli@me.com 

Page 4 of 8 
Appendix 1: Center List 
 
Neurologia e Stroke Unit, Ospedale 
Regionale "U. Parini" 
Aosta (AO) 
Guido Giardini 
ggiardini@ausl.vda.it 
Neurologia Vascolare, Azienda 
Ospedaliera Spedali Civili  
Brescia (BS) 
Mauro Magoni 
mago1959@hotmail.com 
Stroke Unit, Istituto Clinico Città Studi 
 
Milano (MI) 
Carlo Sebastiano Tadeo 
carlosebastiano.tadeo@ic-cittastudi.it 
Neurologia e Stroke Unit, Ospedale 
Santa Maria delle Croci 
Ravenna (RA) 
Pietro Querzani 
pietro.querzani@auslromagna.it 
Stroke Unit, Azienda Ospedale 
Università  
Padova (PD) 
Claudio Baracchini 
claudiobaracchini@gmail.com 
Neurologia, Ospedale San Donato, 
Azienda USL Toscana Sud Est, Arezzo e 
Val D'Arno  
Arezzo (AR) 
Giovanni Linoli 
giovanni.linoli@uslsudest.toscana.it 
Neurologia, Ospedale della Murgia 
Fabio Perinei SS 96 
Altamura-Gravina (BA) 
Bonaventura Ardito 
bonaventura.ardito@asl.bari.it 
Neurologia e Stroke Unit, Ospedale di 
Desio ASST Monza 
Desio (MB) 
Ignazio Santilli 
i.santilli@asst-monza.it 
Neurologia Terapia Sub-Intensiva 
Stroke Unit, Azienda ospedaliera 
Santa Maria di Terni 
Terni (TR) 
Carlo Colosimo 
c.colosimo@aospterni.it 
Medicina e Chirurgia d'Accettazione e 
d'Urgenza Azienda USL 6 Livorno 
Livorno (LI) 
Paolo Pennati 
paolo.pennati@uslnordovest.toscana.it 
Stroke Unit, Ospedale San Giacomo 
 
Novi Ligure (AL) 
Eugenia Rota 
eugenia.rota.md@gmail.com 
Neurologia, Casa sollievo della 
sofferenza  
San Giovanni Rotondo (FG) 
Pietro Di Viesti 
pietro.diviesti@gmail.com 
Neurologia e Stroke Unit Ospedale di 
Legnano 
Legnano (MI) 
Francesco Muscia  
francesco.muscia@asst-ovestmi.it 
Neurologia, Ospedale Fatebenefratelli  Roma (RM) 
Francesco Passarelli 
francescopassarelli54@gmail.com 
Neurologia,Ospedale San Bassiano 
Bassano del Grappa (VI) 
Alessandro Burlina 
alessandro.burlina@aulss7.veneto.it 
Neurologia, San Filippo Neri  
Roma (RM) 
Cinzia Roberti 
cinziaroberti02@gmail.com 
Neurologia, Ospedale F Renzetti 
Lanciano (CH) 
Maurizio Maddestra 
maurizio.maddestra@asl2abruzzo.it 
Clinica neurologica e di riabilitazione, 
Azienda sanitaria universitaria 
integrata 
Udine (UD) 
Gian Luigi Gigli 
gianluigi.gigli@asufc.sanita.fvg.it 

Page 5 of 8 
Appendix 1: Center List 
 
Neurologia e Stroke Unit, 
Sant'Eugenio 
Roma (RM) 
Letizia Cupini  
letiziamaria.cupini@aslroma2.it 
Stroke Unit, Azienda Ospedaliera 
"Bianchi-Melacrino-Morelli"  
Reggio Calabria (RC) 
Luciano Arcudi 
larcudi@libero.it 
Stroke Unit, Ospedale San Martino di 
Belluno ULSS 1 
Belluno (BL) 
Sandro Zambito Marsala 
sandro.zambito@aulss1.veneto.it 
Neurologia, Azienda Ospedaliera 
Cannizzaro  
Catania (CT) 
Maria Giovanna Pennisi 
mariagiovannapennisi@virgilio.it 
Neurologia, AUSL Piacenza,  
Piacenza (PC) 
Donata Guidetti 
d.guidetti@ausl.pc.it 
Clinica Neurologica e Stroke Unit 
Ospedali Riuniti Ancona 
Ancona (AN) 
Giovanna Viticchi 
viticchi.g@gmail.com 
Neurologia Azienda Ospedaliera-
Universitaria di Ferrara 
Ferrara (FE) 
Alessandro De Vito 
aledevito@hotmail.com 
Neurologia INRCA-IRCCS Ospedale "U 
Sestili" 
Ancona (AN) 
Giuseppe Pelliccioni 
g.pelliccioni@inrca.it 
Neurologia e Stroke Unit, Ospedale 
Umberto I  
Siracusa (SR) 
Enzo Sanzaro 
e.sanzaro@asp.sr.it 
Neurologia, Ospedale Sant'Andrea 
Vercelli (VC) 
Cristoforo Comi 
cristoforo.comi@med.uniupo.it 
Neurologia e Stroke Unit, Policlinico 
Tor Vergata 
Roma (RM) 
Marina Diomedi 
marina.diomedi@uniroma2.it 
Stroke Unit, Ospedale Valduce  
 
Como (CO) 
Nicoletta Checcarelli  
nicolettache@yahoo.com 
Neurologia e Stroke Unit, Ospedale 
Civile E. Agnelli 
Pinerolo (TO) 
Carmelo Roberto Labate 
crlabate@aslto3.piemonte.it 
Neurologia e Stroke Unit, Ospedale 
San Giuseppe 
Milano (MI) 
Paola Santalucia 
p_santalucia@hotmail.com 
Neurologia e Stroke Unit 
dell'Ospedale Maggiore, IRCCS Istituto 
delle Scienze Neurologiche di Bologna 
Bologna (BO) 
Andrea Zini 
a.zini@ausl.bologna.it 
Neurologia, Presidio Ospedaliero 
Mirano-Dolo 
Venezia (VE) 
Luigi Bartolomei  
luigi.bartolomei@aulss3.veneto.it 
Stroke Unit, Ospedale Civile 
"S.Agostino-Estense”, Azienda 
Ospedaliera Universitaria di Modena  
Modena (MO) 
Guido Bigliardi 
bigliardi.guido@aou.mo.it 

Page 6 of 8 
Appendix 1: Center List 
 
Neurologia e Stroke Unit, Humanitas 
 
Milano (MI) 
Simona Marcheselli 
simona.marcheselli@humanitas.it 
Neurologia e Stroke Unit, Azienda 
Ospedialiera "G. Brotzu" 
Cagliari (CA) 
Jessica Moller 
jessicamoller@aob.it 
Stroke Unit, Ospedale San Martino di 
Genova 
Genova (GE) 
Laura Malfatto 
laura.malfatto@hsanmartino.it 
Stroke Unit, Azienda Ospedaliera 
Universitaria Gaetano Martino 
Messina (ME) 
Rosa Musolino 
rosa.musolino@unime.it 
Neurologia, Ospedale Cà Foncello 
Treviso (TV) 
Simone Tonello 
tonello74@gmail.com 
Neurologia, Ospedale Apuane, 
Azienda USL Toscana Nord Ovest 
Massa (MS) 
Alberto Chiti 
alberto.chiti@uslnordovest.toscana.it 
Neurologia, Ospedale di Conegliano 
Aulss 2 Veneto 
Conegliano (TV) 
Anna Gaudenzi 
anna.gaudenzi@aulss2.veneto.it 
Neurologia, Ospedale SS Giovanni e 
Paolo, Aulss3 Serenissima Veneto  
Venezia (VE) 
Agnese Tonon 
agnese.tonon@aulss3.veneto.it 
Neurologia e Stroke Unit, ARNAS 
Civico di Palermo 
Palermo (PA) 
Serena Monaco 
s.monaco65@gmail.com 
Neurologia, Policlinico Gemelli 
 
Roma (RM) 
Giovanni Frisullo 
giovanni.frisullo@policlinicogemelli.it 
Neurologia, Ospedale San Giacomo 
Castel Franco Veneto (TV) 
Bruno Marini 
bruno.marini@aulss2.veneto.it 
Neurologia, Ospedale Madonna del 
Soccorso 
San Benedetto del Tronto (AP) 
Cristina Paci 
Cristina.Paci@sanita.marche.it 
Stroke Unit, Azienda Ospedaliera San 
Sebastiano AORN Caserta 
Caserta (CE) 
Gioacchino Martusciello 
martugol@yahoo.it 
Neurologia, Azienda Ospedaliera 
Nazionale SS Biagio e Cesare Arrigo 
Alessandria (AL) 
Luigi Ruiz 
lruiz@ospedale.al.it 
Stroke Unit, Fidenza AUSL PR 
 
Fidenza (PR) 
Doriana Medici 
dmedici@ausl.pr.it 
Stroke Unit, Ospedale del Mare 
Napoli (NA) 
Maria Pia Mazzaferro 
mariapia.mazzaferro@libero.it 
Stroke Unit, Azienda ospedaliera 
universitaria San Luigi Gonzaga 
Orbassano (TO) 
Roberto Ferri 
r.ferri@sanluigi.piemonte.it 
Neurologia e Stroke Unit, Ospedale 
San Giovanni Bosco 
Torino (TO) 
Roberto Cavallo 
roberto.cavallo@aslcittaditorino.it 
Neurologia e Stroke Unit, IRCCS 
Istituto Auxologico Italiano, Ospedale 
San Luca 
Milano (MI) 
Laura Adobbati 
laura.adobbati@auxologico.it 

Page 7 of 8 
Appendix 1: Center List 
 
Neurologia e Stroke Unit Cittadella, 
AULSS6 Euganea  
Cittadella (PD) 
Giampietro Ruzza 
giampietro.ruzza@aulss6.veneto.it 
Neurologia, Azienda Sanitaria 
Universitaria Giuliano Isontina (ASUGI) Gorizia (GO) 
Michele Rana 
michele.rana@asugi.sanita.fvg.it 
Stroke Unit, Ospedale dell’Angelo  
 
Mestre (VE) 
Adriana Critelli 
adricry@libero.it 
Neurologia, Ospedale della Valle del 
Serchio 
Lucca (LU) 
Daniele Orsucci 
daniele.orsucci@uslcentro.toscana.it 
Stroke Unit, Ospedale Buccheri La 
Ferla 
Palermo (PA) 
Aurelio Piazza 
aurelio.piazza@email.it 
Neurologia, Azienda Cardio-toraco-
neuro-vascolare USL Toscana sud est Grosseto (GR) 
Roberto Marconi 
roberto2.marconi@uslsudest.toscana.it 
Neurologia, Fondazione Istituto G. 
Giglio di Cefalù  
Cefalù (PA) 
Luigi Grimaldi 
luigi.grimaldi@hsrgiglio.it 
Centro Ictus, USL umbria 1 
Città di Castello (PG) 
Silvia Cenciarelli 
silvia.cenciarelli@uslumbria1.it 
Centro Ictus, Ospedale Gubbio-Gualdo 
Tadino  
Branca (PG) 
Tatiana Mazzoli 
tatiana.mazzoli@uslumbria1.it 
Stroke Unit, Ospedale Santa Chiara 
Trento (TN) 
Valeria Bignamini 
valeria.bignamini@apss.tn.it 
Stroke Unit, Ospedale Pederzoli 
Peschiera del Garda (VR) 
Domenico Idone 
domenicoidone1962@gmail.com 
Neurologia Mirano ULSS 3 Serenissima Mirano (VE) 
Maela Masato 
maelamasa@gmail.com 
Neurologia, Ospedale Sant’Orsola 
Bologna (BO) 
Marina Guarino 
maria.guarino@aosp.bo.it 
Neurologia, Azienda Ospedaliera San 
Pio 
Benevento (BN) 
Marco Sparaco 
marcosparaco@alice.it 
Unità di trattamento neurovascolare, 
Ospedale Santa Maria Goretti 
Latina (LT) 
Gabriella Monteforte 
g.monteforte@ausl.latina.it 
Neurologia e Stroke, Unit ASST 
Ospedale Maggiore di Crema 
Crema (CR) 
Luigi Caputi 
luigi.caputi@asst-crema.it 
Stroke Unit, Ospedale Santa Croce 
Moncalieri (TO) 
Marco De Mattei 
demattei.marco@aslto5.piemonte.it 
Neurologia, Ospedale F Renzetti 
Rimini (RN) 
Enrico Maria Lotti 
enricomaria.lotti@auslromagna.it 

Page 8 of 8 
Appendix 1: Center List 
 
Neurologia e Stroke Unit, Azienda 
Sanitaria Provinciale Trapani  
Trapani (TP) 
Luigi Sicurella 
luigi.sicurella@libero.it 
Neurologia e Stroke Unit, Ospedale S 
Elia 
Caltanissetta (CL) 
Maria Giovanna Randisi 
giovannarandisi@gmail.com 
 

08/02/2021 9:15pm
projectredcap.org
Confidential
Page 1
Baseline CRF
Please fill in the survey to record baseline characteristic of your patient.
Please notice that patients, who early discontinue the dual antiplatelet treatment SHOULD be included.
 
Please refer to this link for the study protocol, CRF instructions and more useful
tools:https://drive.google.com/drive/folders/1vdMcXNSho0lFpv2AcZ1f8ArnrJPNoG33?usp=sharing
1. DEMOGRAPHICS
Center and patient's code (please note the code on
patient's documents, it will be necessary for the
__________________________________
follow-up CRF)
(Please insert the XXX code of the center followed
by patient's number 000)
Was the patient hospitalized?
Yes
No
Duration of the hospitalization (days)
__________________________________
Gender
Male
Female
Race
White
Black
Asian
Other
Date of birth
__________________________________
Height (cm)
__________________________________
Weight (kg)
__________________________________
Body Mass Index (kg/m^2)
__________________________________
(This field is automatically calculated)

08/02/2021 9:15pm
projectredcap.org
Confidential
Page 2
2. RISK FACTORS, COMORBIDITIES AND MEDICAL HISTORY
Current or previous cigarette smoker
Yes
No
Smoking status
Current
Former
Arterial hypertension
Yes
No
Diabetes mellitus
Yes
No
Hypercholesterolemia
Yes
No
Hypertriglyceridemia
Yes
No
History of cancer
Yes-current
Yes-past *
No
(* absence of disease in the past 5 years,
otherwise consider the option "current")
Type of cancer
Gastrointestinal cancer
Lung cancer
Prostate cancer
Breast/ovarian cancer
Hematopoietic/lymphoid cancer
Skin cancer
Other
Previous history of ischemic stroke or TIA
Yes
No
Type of previous ischemic event 
Ischemic stroke
TIA
Previous history of intracerebral hemorrhage
Yes
No
Location of previous intracerebral hemorrhage
Lobar
Non-lobar
Uncertain
(For
the
classification
please
refer
to
https://discovery.ucl.ac.uk/id/eprint/1535936/1/Werring_The
History of myocardial infarction
Yes
No

08/02/2021 9:15pm
projectredcap.org
Confidential
Page 3
History of angina
Yes
No
Congestive heart failure
Yes
No
Valvular heart disease
Yes
No
Peripheral artery disease
Yes
No
Vascular disease (prior myocardial infarction,
peripheral vascular disease or aortic plaque)
__________________________________
(This field is automatically calculated)
3. PREVIOUS OR CONCOMITANT MEDICATIONS
Was the patient taking aspirin before the event?
Yes
No
Was the patient taking clopidogrel before the event?
Yes
No
Was the patient taking ticagrelor before the event?
Yes
No
Was the patient taking a statin before the event?
Yes
No
Was the patient taking any antihypertensive before
Yes
the event?
No
Was the patient taking any antidiabetic treatment
Yes
before the event?
No
modified Rankin Scale score before the event
__________________________________
4. INDEX EVENT
Date of the event
__________________________________
Was the event related to a procedure (event occurring
Yes
after endarterectomy, coronary stenting, or any
No
other procedure)?
Systolic blood pressure  (mmHg)
__________________________________
Diastolic blood pressure (mmHg)
__________________________________

08/02/2021 9:15pm
projectredcap.org
Confidential
Page 4
Symptoms duration
>24 h
< 24 h
Presence of a lesion  in CT or MRI scan consistent
Yes
with symptoms
No
NIHSS score at onset or before any acute procedure
__________________________________
(In case of TIA please report 0)
Was the patient treated with intravenous
Yes
thrombolysis?
No
Was the patient treated with endovascular treatment?
Yes
No
Was the patient treated with carotid endoarterectomy?
Yes
No
Days from onset to carotid endoarterectomy
__________________________________
Hemorragic infarction 
Yes asymptomatic
Yes symptomatic (sICH)
No
Unknown
(sICH defined according to SITS-MOST: Parenchymal
hematoma H2 or Parenchymal hematoma r2 on imaging
22 to 36 hours after treatment, or earlier if
scanned because of clinical deterioration,
combined with a neurologic deterioration of ≥4
NIHSS points or leading to death within 24 hours
(Neurology 2015;85:2098-2106))
Classification of hemorragic infarction
HI1: Scattered small petechiae, no mass effect
HI2: Confluent petechiae, no mass effect
PH1: Hematoma within infarcted tissue, occupying <
30%, no substantive mass effect
PH2: Hematoma occupying 30% or more of the
infarcted tissue, with obvious mass effect
PH remote from infarcted brain tissue
Intraventricular hemorrhage
Subarachnoid hemorrhage
Subdural hemorrhage
(PH= parenchymal hematoma; HI=Hemorragic
infarction REFERENCE: Stroke. 2015;46:2981-2986.)
Date of hemorragic infarction
__________________________________
Days to hemorragic infarction
__________________________________
(This field is automatically calculated)
NIHSS score at 24 h from onset
__________________________________

08/02/2021 9:15pm
projectredcap.org
Confidential
Page 5
modified Rankin scale at discharge
__________________________________
4.1. CLINICAL PRESENTATION
Symptoms of the event (select all that apply)
Motor weakness
Aphasia
Dysarthia
Sensory disturbance
Visual field defect
Diplopia
Vertigo
Loss of balance
Monocular visual loss
Other
Symptom location
Unknown
Right hemisphere or eye
Left hemisphere or eye
Posterior circulation
Multiple vascular districts
Age
__________________________________
(This field is automatically calculated)
Age ≥60 years
__________________________________
(This field is automatically calculated)
Age 65-74 years
__________________________________
(This field is automatically calculated)
Age ≥75 years
__________________________________
(This field is automatically calculated)
BP ≥140/90 mmHg
Yes
No
(Initial BP. Either SBP ≥ 140 or DBP ≥ 90)
Clinical features of the TIA
Unilateral weakness
Speech disturbances without weakness
Other symptoms
Duration of TIA symptoms
< 10 minutes
10-59 minutes
≥60 minutes
ABCD₂ score
__________________________________
(This field is automatically calculated)
CHA₂DS₂-VASc
__________________________________
(This field is automatically calculated)

08/02/2021 9:15pm
projectredcap.org
Confidential
Page 6
4.2 EXAMINATIONS
Examinations performed (select all that apply)
ECG
Epiaortic doppler ultrasonography
CT extracranial angiography
MRI extracranial angiography
Transcranial doppler
CT intracranial angiography
MRI intracranial angiography
Angiography
Transthoracic echocardiogram
Transthoracic echocardiogram with bubble study
Transesophageal echocardiogram
Transesophageal echocardiogram with bubble study
Immunologic screening
Coagulation screening
Brain CT
Yes
No
Brain CT timing
Acute (within 24h from onset) only
Follow-up (24h or more from onset) only
Both acute and follow-up
CT markers of small vessel disease
Leukoaraiosis
Prior lacunar infarcts (asymptomatic)
None
(REFERENCE: Neurol 2020;94:e439-e452)
Leukoaraiosis severity (anterior regions)
No lucency
Lucency restricted to region adjoining ventricles
Lucency covering entire region from lateral
ventricle to cortex
(REFERENCE: Neurol 2020;94:e439-e452)
Leukoaraiosis severity (posterior regions)
No lucency
Lucency restricted to region adjoining ventricles
Lucency covering entire region from lateral
ventricle to cortex
(REFERENCE: Neurol 2020;94:e439-e452)
Leukoaraiosis score
__________________________________
(This field is automatically calculated)
Ischemic lesion volume at brain CT (ml)
__________________________________
(Estimated on the brain CT performed after the
acute phase by the ABC/2 method. Reference can be
found here:
https://radiopaedia.org/articles/abc2. Please
report "0" if lesion is absent.)
Brain MRI
Yes
No
Number of acute lesions at brain MRI
None
One
Two
More than two

08/02/2021 9:15pm
projectredcap.org
Confidential
Page 7
Were the lesions in the same vascular territory?
Yes
No
MRI markers of small vessel disease (select all that
White matter hyperintensity
apply)
Lacune
Perivascular space
Cerebral microbleeds
Brain atrophy
Cortical superficial siderosis
None
(REFERENCE: Lancet Neurol 2013 Aug;12(8):822-38)
Fazekas scale for white matter lesions
No white matter lesions (grade 0)
(periventricular white matter)
"Caps" or pencil-thin lining (grade 1)
Smooth "halo" (grade 2)
Irregular periventricular signal extending into
the deep white matter (grade 3)
(REFERENCE:
https://radiopaedia.org/articles/fazekas-scale-for-white-mat
Fazekas scale for white matter lesions (deep white
No white matter lesions (grade 0)
matter)
Punctate foci (grade 1)
Beginning confluence (grade 2)
Large confluent areas (grade 3)
(REFERENCE:
https://radiopaedia.org/articles/fazekas-scale-for-white-mat
Ischemic lesion volume at brain MRI (ml)
__________________________________
(Estimated  by the ABC/2 method. If multiple acute
lesions, consider the larger one. Reference can
be found here:
https://radiopaedia.org/articles/abc2.  Please
report "0" if lesion is absent.)
Electrocardiography monitoring
Yes
No
Duration of electrocardiography monitoring
< 24 hours
24 hours-7 days
7-30 days
>30 days
5. CAUSE OF THE EVENT
Presence of right carotid stenosis/occlusion
Yes
No
Unknown (not performed examinations to explore
extracranial arteries)
Degree of right carotid stenosis
1-30%
31-49%
50-69%
70-99%
Occlusion

08/02/2021 9:15pm
projectredcap.org
Confidential
Page 8
Presence of left carotid stenosis/occlusion
Yes
No
Unknown (not performed examinations to explore
extracranial arteries)
Degree of left carotid stenosis
1-30%
31-49%
50-69%
70-99%
Occlusion
Presence of vertebrobasilar stenosis/occlusion
Yes
No
Vertebrobasilar stenosis/occlusion
Right vertebral artery
Left vertebral artery
Basilar artery
Presence of intracranial stenosis?
Yes
No
Unknown (not performed examinations to explore
intracranial arteries)
Symptomatic intracranial stenosis (i.e. consistent
Yes
with symptoms of index event)?
No
Presence of aortic arch plaque?
Yes
No
Unknown
Presence of patent foramen ovale (PFO)?
Yes
No
Unknown
(PFO identified through transthoracic,
transesophageal echocardiography or transcranial
doppler with bubble study)
Other anatomic features associated with PFO
Atrial septal aneurysm
Hypertrophy of the interatrial septum
Presence of the Eustachian valve
Aortic root dilation
Other
Severity of the shunt 
1-10 MES small shunt
> 10 MES medium shunt
> 10 MES with "curtain effect," large shunt
Cause of the event
Large vessel stroke
Lacunar stroke
Stroke or TIA due to other defined cause
Stroke or TIA of undetermined cause
(In case of PFO check "stroke of undetermined
cause")
Other determined cause:
dissection
vasculitis
hypercoagulable state
other

08/02/2021 9:15pm
projectredcap.org
Confidential
Page 9
Undetermined cause:
more than one probable cause
negative evaluation
incomplete evaluation
Does the event fulfill the characteristics of ESUS?
Yes
No
Not applicable (required examinations not
performed)
(DEFINITION: Non-lacunar ischemic stroke; absence
of atherosclerosis causing >50% stenosis in
arteries supplying ischemic area; no major risk
cardioembolic source, no other specific cause of
stroke identified. REQUIRED EXAMINATIONS: imaging
of the brain, intra- and extracranial vessels,
12-lead ECG, ≥24h cardiac monitoring, and
precordial echocardiography. REFERENCE: Lancet
Neurol 2014;13:429-438.)
6. ANTIPLATELET TREATMENT
Type of dual antiplatelet treatment  
clopidrogrel and aspirin
ticagrelor and aspirin
Timing of initiation of dual antiplatelet treatment
< 12 h
12-24 h
25-48 h
>48 h
Did the patient receive a loading dose of aspirin?
Yes
No
Did the patient receive a clopidogrel loading dose?
Yes
No
Did the patient receive a ticagrelor loading dose?
Yes
No

08/02/2021 9:14pm
projectredcap.org
Confidential
Page 1
Follow-up CRF
Please complete the survey below adding the follow-up data of your patients.
Thank you!
Please refer to this link for the study protocol, CRF instructions and more useful
tools:https://drive.google.com/drive/folders/1vdMcXNSho0lFpv2AcZ1f8ArnrJPNoG33?usp=sharing
Center and patient's code (please insert the code
reported on the baseline CRF)
__________________________________
(Please insert the XXX code of the center followed
by patient's number 000)
Lost to follow-up?
Yes
No
1. ANTIPLATELET TREATMENT DURATION
Date of dual antiplatelet treatment start
__________________________________
Was the patient compliant with the prescribed dose
Yes
and duration of dual antiplateletet?
No
Did the patient early discontinue the treatment with
Yes
dual antiplatelet? 
No
Which was the antiplatelet discontinued? (Select all
Cardioaspirin
that apply)
Ticagrelor/clopidogrel
Reason for early dual antiplatelet discontinuation
Adverse events
Lack of compliance
Diagnosis of atrial fibrillation or other
condition requiring anticoagulant treatment
Other
Adverse event leading to discontinuation
Allergic reaction
Bleeding
Duration of treatment with dual antiplatelet (days)
__________________________________
Antiplatelet prescribed after DAPT cessation
Aspirin
Clopidogrel
Ticagrelor
None

08/02/2021 9:14pm
projectredcap.org
Confidential
Page 2
2. VISIT DETAILS, COMPLIANCE TO TREATMENTS AND OTHER THERAPEUTIC PROCEDURES
Date of follow-up visit
__________________________________
Type of visit 
On site
Remote
Yes
No
N/A (not prescribed)
Compliance to antihypertensives
Compliance to statins
Compliance to antidiabetics
Did the patient undergo endarterectomy?
Yes
No
N/A (not applicable)
Did the patient undergo PFO closure?
Yes
No
N/A (not applicable)
3. OUTCOMES
Ischemic stroke or TIA
Yes
No
Symptoms duration
>24 h
< 24 h
Presence of a lesion  in CT or MRI scan consistent
Yes
with symptoms?
No
Date of ischemic event
__________________________________
Days to ischemic event
__________________________________
(This field is automatically calculated)
Symptom location
Unknown
Right hemisphere or eye
Left hemisphere or eye
Posterior circulation
Multiple vascular districts
NIHSS score of ischemic stroke at onset
__________________________________
(In case of TIA please report 0)
Clical features of TIA
Unilateral weakness
Speech disturbances without weakness
Other symptoms
Duration of TIA symptoms
< 10 minutes
10-59 minutes
≥60 minutes

08/02/2021 9:14pm
projectredcap.org
Confidential
Page 3
Cause of the ischemic stroke or TIA
Large vessel stroke
Lacunar stroke
Cardioembolism
Stroke or TIA due to other defined cause
Stroke or TIA of undetermined cause
Other determined cause of the ischemic stroke or TIA
dissection
vasculitis
hypercoagulable state
other
Undetermined cause 
more than one probable cause
negative evaluation
incomplete evaluation
Does the ischemic stroke fulfill the characteristics
Yes
of ESUS?
No
Not applicable (required examinations not
performed)
(DEFINITION: Non-lacunar ischemic stroke; absence
of atherosclerosis causing >50% stenosis in
arteries supplying ischemic area; no major risk
cardioembolic source, no other specific cause of
stroke identified. REQUIRED EXAMINATIONS: imaging
of the brain, intra- and extracranial vessels,
12-lead ECG, ≥24h cardiac monitoring, and
precordial echocardiography. REFERENCE: Lancet
Neurol 2014;13:429-438.)
Intracerebral hemorrage
Yes
No
Date of intracerebral hemorrhage
__________________________________
Days to intracerebral hemorrhage
__________________________________
(This field is automatically calculated)
NIHSS score of intracerebral hemorrhage at onset
__________________________________
Intracerebral hemorrhage location
Lobar
Non-lobar
Uncertain
(For
the
classification
please
refer
to
https://discovery.ucl.ac.uk/id/eprint/1535936/1/Werring_The

08/02/2021 9:14pm
projectredcap.org
Confidential
Page 4
Intracerebral hemorrhage cause
Probable amyloid angiopathy (lobar location AND
age >55 years)
Hypertensive angiopathy (SBP>160mmHg OR
DBP>100mmHg OR history of antihypertensive
medication)
Other/Unknown
(Hypertensive patients aged >55 years and with
lobar ICH are included in the "Probable amyloid
angiopathy" category)
Subarachnoid hemorrage
Yes
No
Date of subarachnoid hemorrhage
__________________________________
Days to subarachnoid hemorrhage
__________________________________
(This field is automatically calculated)
Other intracranial bleeding 
Yes
No
(Intracranial bleeding is an hemorrage within the
cranial vault regardless the etiology)
Type of intracranial bleeding
Subdural hematoma
Epidural hematoma
Other
(Intracranial bleeding is an hemorrage within the
cranial vault regardless the etiology)
Date of intracranial bleeding
__________________________________
(Intracranial bleeding is an hemorrage within the
cranial vault regardless the etiology)
Days to intracranial bleeding
__________________________________
(This field is automatically calculated)
Myocardial infarction
Yes
No
Date of myocardial infarction
__________________________________
Days to myocardial infarction
__________________________________
(This field is automatically calculated)
Vascular death (i.e. death due to stroke (ischemic or
Yes
hemorrhagic), systemic hemorrhage, myocardial
No
infarction, congestive heart failure, pulmonary
embolism, sudden death, or arrhythmia)
Date of vascular death
__________________________________

08/02/2021 9:14pm
projectredcap.org
Confidential
Page 5
Days to vascular death
__________________________________
(This field is automatically calculated)
Non-vascular death (i.e. death occurring for any
Yes
cause different from those of the previous variable)
No
Date of non-vascular death
__________________________________
Days to non-vascular death
__________________________________
(This field is automatically calculated)
Any hospitalization
Yes
No
Date of hospitalization
__________________________________
Days to hospitalization
__________________________________
(This field is automatically calculated)
Severe bleeding (i.e. fatal hemorrage or hemorrhage
Yes
causing hemodynamic compromise that required blood
No
or fluid replacement, inotropic support, or surgical
intervention)
Date of severe bleeding
__________________________________
Days to severe intracranial bleeding
__________________________________
(This field is automatically calculated)
Moderate bleeding (i.e. bleeding that required
Yes
transfusion of blood but did not lead to hemodynamic
No
compromise requiring intervention)
Date of moderate bleeding
__________________________________
Days to moderate bleeding
__________________________________
(This field is automatically calculated)
Minor bleeding (i.e. any bleeding not requiring blood
Yes
transfusion and not leading to hemodynamic compromise)
No
Date of minor bleeding
__________________________________
Days to minor bleeding
__________________________________
(This field is automatically calculated)

08/02/2021 9:14pm
projectredcap.org
Confidential
Page 6
modified Rankin Scale score at 90 days
__________________________________