Selective Coronary Revascularization in Carotid Artery Disease Patients After Carotid Revascularization (SCORECAD Trial)
Conditions: Carotid Stenosis, Coronary Artery Disease
Sponsor: Pauls Stradins Clinical University Hospital

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 PROTOCOL 
 
 
Selective  Coronary Revascularization in Carotid Artery Disease patients after 
carotid revascularization  (SCORECAD trial) 
 
 
 
Working draft protocol version number:  Latvia RCT/CAD/25062024 
Universal Trial Number:   ClinicalTrials.gov TBA 
 
In the following, Institute of Science, Pauls Stradins Clinical University Hospital and its affiliates will 
be stated as <Stradins University Hospital=. 
This confidential document is the property of Stradins university hospital. No unpublished information 
contained herein may be disclosed without prior written approval from Stradins university hospital. 
Access to this document must be restricted to relevant parties. 
 
 
DOCUMENT HISTORY 
Document version 
Date 
Applicable in country(-ies) 
and/or site(s) 
1.0 
25 June 2024 
All 
 
 
 
 
 
Study Objective 
To determine whether the diagnosis of  ischemia-producing coronary 
stenosis together with selective coronary revascularization in carotid 
artery stenosis (CAS) patients following carotid revascularization can 
reduce adverse cardiac events and improve survival compared to carotid 
patients receiving standard cardiac evaluation and treatment.  
 
Study Design 
Multicenter, prospective randomized clinical trial of patients with 
symptomatic or asymptomatic CAS patients, and no known CAD who 
had undergone a carotid revascularization procedure (endarterectomy or 
stenting).  Eligible patients will be randomly assigned to receive (a) 
current guideline-directed care with evidence-based best medical 
therapy (BMT) and risk factor control or (b) in addition to BMT and 

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risk factor control, non-invasive cardiac evaluation using coronary CTA 
and FFRct to identify ischemia-producing coronary lesions together 
with  selective ischemia-targeted coronary revascularization.  The 
primary outcome measure will be MACE (cardiac death, myocardial 
infarction, urgent (unplanned) coronary revascularisation)  during 2 
years follow up with secondary endpoints of myocardial infarction, 
cardiac death, urgent coronary revascularisation, cardiovascular death 
and all-cause death.  
 
Principal 
Investigator: 
  
Dainis Krievins, MD, PhD   and principal Co-investigator Andrejs 
Erglis MD, PhD 
Pauls Stradins Clinical University hospital 
13 Pilsonu street 
Riga, Latvia. LV-1002 
Dainis.krievins@gmail.com; dainis.krievins@stradini.lv 
+371 29450000; +371 67069604 
 
Co-investigators & Steering committee:  Christopher K. Zarins 
MD; Gustavs Latkovskis MD, PhD; Indulis Kumsars MD, PhD; 
Peteris Stradins MD, PhD; Sanda Jegere MD, PhD; Patricija 
Ivanova MD, PhD and others TBA. 
 
 
 
Study Sites:  
 
Pauls Stradins Clinical University Hospital plus up to 10 additional sites  
 
 
CRO:   
Institute of Science, Pauls Stradins Clinical University Hospital  
 
 
 
 
 
Study Sponsor: 
 
Pauls Stradins Clinical University Hospital with a grant from the TBA. 

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I.   BACKGROUND 
 
Coronary artery disease (CAD) is the primary cause of morbidity and mortality in patients with carotid 
artery disease.  Patients with asymptomatic carotid stenosis have a four-fold higher risk of myocardial 
infarction (MI) than stroke1 and the presence of carotid stenosis is an independent predictor of cardiac 
death.2,3  Patients undergoing carotid endarterectomy (CEA) have a higher risk of myocardial infarction 
(MI) than stroke and those with post-op MI have a 5 year survival of only 56%.4  Despite this high 
cardiac risk and the knowledge that 60% of carotid endarterectomy patients have coronary angiographic 
evidence of significant CAD (>70% stenosis),5 systematic pre-operative cardiac testing is not 
recommended for vascular surgery patients since randomized trials have shown no long-term survival 
benefit from pre-operative coronary revascularization.6 Guidelines specifically note that cardiac testing 
should not be performed in patients with no coronary symptoms7 and thus most patients undergo major 
vascular surgery without pre-operative cardiac testing and mortality of patients with post-op MI remains 
high despite evidence-based medical therapy.8  
     
    Myocardial ischemia is common in patients with CAD, is often asymptomatic (silent), and is a marker 
for adverse cardiac events and reduced survival.9 Pre-operative non-invasive testing of patients 
undergoing carotid or peripheral vascular surgery showed that 25-40% of patients had silent ischemia 
and that silent ischemia was a predictor of adverse outcomes.10-12 While cardiac stress testing provides 
valuable information on myocardial perfusion, it does not provide actionable information regarding 
coronary artery lesions which may be producing ischemia and which may benefit from 
revascularization.  The ischemic potential of a coronary stenosis can be determined at the time of 
coronary angiography by measurement of fractional flow reserve (FFR).  Randomized trials of patients 
with stable CAD and lesion-specific coronary ischemia as demonstrated by FFRf0.80 in at least one 
large coronary artery have shown that FFR-guided coronary revascularization results in a significant 
reduction in death/MI at 5 years compared to medical therapy.13,14 
 
  
     A newly introduced non-invasive diagnostic modality, coronary CT-derived fractional flow reserve 
(FFRCT) provides a unified anatomic and functional assessment of coronary artery disease which can 
reliably identify ischemia-producing coronary lesions.15 FFRCT analysis is based on anatomic 
information provided by coronary CTA with computational analysis of coronary blood flow to provide 
fractional flow values throughout the coronary tree. FFRCT accurately reflects invasively measured 
FFR16 and can help guide patient management decisions.17,18 The clinical usefulness of FFRCT is well 
documented19 and FFRCT analysis is now being used in the US, Europe, Canada and Japan to evaluate 
stable patients with symptoms of CAD.  The usefulness of FFRCT in evaluation of patients without 
cardiac symptoms is unknown.   
In a prospective, single-center, observational study of patients with no known CAD undergoing CEA, a 
strategy of pre-operative cardiac evaluation using coronary CTA and FFRCT, along with ischemia-
guided coronary revascularization following CEA, resulted in a more than 50% reduction in all-cause 

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death, cardiac death, myocardial infarction, and MACE, with improved 5-year survival compared to 
patients receiving standard cardiac evaluation and care (84% vs 64%, p<.001)20-21. 
The purpose of this study is to determine the prevalence of silent coronary ischemia in patients 
undergoing carotid revascularization (endarterectomy of stenting) using coronary CTA and FFRCT and 
to evaluate the potential usefulness of FFRCT in selecting patients for coronary revascularization to 
reduce cardiac events and improve survival.       
 
 
 
II. OBJECTIVE 
 
    The primary objective of this study is to determine whether among symptomatic and asymptomatic  
CAS patients with no known CAD who had undergone carotid artery revascularization (endarterectomy 
of stenting) a strategy of best medical therapy (BMT) plus selective coronary revascularization based on 
FFRct assessment of lesion-specific coronary ischemia can reduce adverse cardiac events and improve 
survival compared to BMT alone.  Lesion-specific coronary ischemia is defined as FFRCT  f0.80 distal 
to stenosis in a major (g2 mm) coronary artery with severe ischemia defined as  FFRCT  f0.75. 
 
III. STUDY ENDPOINTS 
 
    The primary endpoint of the study is a composite of cardiac death, myocardial infarction (MI) or urgent 
(unplanned) coronary revascularisation (MACE) during 2 years follow up.  Secondary endpoints include 
cardiac death, MI, urgent coronary revascularisation, cardiovascular (CV) death, all-cause death during 
follow up.   
     
 
IV.  STUDY DESIGN  
 
    This study targets a population of patients with symptomatic or asymptomatic carotid artery stenosis 
(CAS) (symptomatic to asymptomatic in 1:1 ratio) and no prior cardiac history, no myocardial infarction, 
no coronary angiography or coronary CTA, and no coronary revascularization (PCI or CABG) who have 
undergone successful carotid artery revascularisation with planned post-operative best medical therapy.  
Within 14 days following carotid revascularisation, patients will be randomly assigned to BMT alone or 
BMT plus coronary CT angiography (which must be completed within 14 days of randomization) and 
FFRct analysis to determine the functional significance of coronary lesions identified on the CT scan.   
Results of the CT scan and FFRCT analysis in patients randomized to the CT-FFRct group, will be provided 
to treating physicians to help guide patient management with Vascular Heart Team consideration for 
coronary angiography and revascularization as appropriate for each patient. Coronary revascularisation 
(PCI or CABG), if indicated, is strongly reccomended within 3 months from the randomisation. Clinical 
follow up (based on date of randomization) is planned 6 months, one and 2 years. Additional long-term 
follow up out to 5-years is planned for participating centers.  An independent academic clinical events 
committee will adjudicate all endpoints in a blinded manner. The definition of outcome events will be in 

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accordance with Academic Research Consortium-2 consensus document22.  Sample size power 
calculations assumed a hazard ratio of 0.5 with estimated sample size up to 300 patients (up to 150 in each 
group), 90% power, alpha .05.  The patient sample size may be reduced if statistical significance been 
achieved.  
 
 
 
V. INCLUSION AND EXCLUSION CRITERIA 
 
 
Inclusion Criteria 
 
 
1. Inform consent obtained before any study-related activities 
2. Age above or equal to 50 years with symptomatic or asymptomatic critical carotid stenosis 
(symptomatic patients with at least Rankin III.) which has been successfully revascularized by 
carotid endarterectomy or stenting within the past 14 days  
3. Willing and able to undergo coronary CTA scan within 14 days of randomization and agrees to 
submission of CTA data set for HeartFlow FFRct analysis with results made available to treating 
physician 
 
 
Exclusion Criteria 
  
1. Known CAD, history of MI, prior coronary revascularization (PCI or CABG)  
2. Patient underwent coronary angiography or coronary CTA before the randomization  
3. Known hystory of 2nd or 3rd degree heart block; sick sinus syndrome; long QT syndrome  
4. History of severe asthma, severe or bronchodilator-dependent COPD 
5. Severe congestive heart failure (NYHA III or IV) 
6. Severe arrhythmia, prior pacemaker or internal defibrillator lead implantation 
7. Impaired chronic renal function (EPI-GFR<30ml/min)  
8. Subjects with known anaphylactic allergy to iodinated contrast 
9. Pregnancy or unknown pregnancy status in subject of childbearing potential 
10. Evidence of ongoing or active clinical instability, including acute chest pain (sudden onset), 
cardiogenic shock, unstable blood pressure with systolic blood pressure <90 mmHg, or acute 
pulmonary edema 
11. Any active, serious, life-threatening disease with a life expectancy of less than 2 years 
12. Any active infection 
13. Inability to comply with study procedures 
14. Contraindication for guideline-guided longterm antiplatelet/anticoagulation regime after 
PCI/CABG 
15. Large neurologic deficit (Rankin scale >III) 

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16. Participation in any interventional clinical study within 30 days prior to screening 
 
 
 
VI. Rules for subject withdrawal and terminating the study 
 
In accordance with the Declaration of Helsinki, as amended, each subject is free to withdraw from the 
study at any time. Investigator(s) also have the right to withdraw subjects from the study in the event of 
illness, adverse events (AEs), serious adverse events (SAEs), other reasons concerning the health or well 
being of the subject, or in the case of lack of cooperation. The reason for withdrawal must be noted in the 
Case Report Forms (CRFs). If the reason for withdrawal is a clinical AE or SAE, follow up of the subject 
will continue until the outcome is evident. The specific event or test result(s) must be recorded in the 
CRFs. 
 
There are no formal termination criteria for this study. The sponsor reserves the right to terminate the 
study at any time. Investigators have the responsibility to comply with International Conference on 
Harmonization E6-Good Clinical Practice (ICH E6 - GCP) guidance. The sponsor, the IRB, or the health 
authorities may terminate a center for the following (but not limited to) reasons:  
1) Failure of the investigator to comply with pertinent E6-GCP guidelines and regulations  
2) Serious protocol violations  
3) Submission of knowingly false information from the research facility.  
 
VII.  Ethical Considerations  
 
The potential benefits to all subjects participating in this study is that they may receive closer monitoring 
and follow up with better compliance to guideline-recommended BMT and risk factor control. Patients 
randomized to the coronary CTA-FFRct arm of the study will have additional benefit of specific cardiac 
diagnosis and treatment. Prior studies have demonstrated that PAD patients often have unrecognized 
coronary artery disease and that they have a high risk of cardiovascular complications including MI and 
cardiovascular death.  Current guideline-directed pre-procedure cardiac evaluation of  PAD patients 
without cardiac symptoms does not include cardiac imaging or stress testing.  Half of enrolled subjects 
within the study will undergo coronary artery CT scanning which is highly sensitive for detecting CAD. 
Subsequent  FFRct analysis will identify those with hemodynamically significant coronary stenosis.   The 
incremental potential risks to subjects participating in the study are solely and directly related to the 
performance of the additional cardiac diagnostic testing in half of the patients. 
 
 
 
 
VIII.A.  Risks of  Coronary CTA 
 
Coronary CTAs expose subjects to small amounts of ionizing radiation. Since the introduction of 64-
detector row CTA scanners in 2005, numerous radiation dose reduction methods have been developed 
which now permit CTA performance with low overall radiation dose. Minimization of radiation dose 
while preserving image quality is a goal of the study; optimization of radiation dose may be achieved by 

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a by a combination of 7 additive dose reduction strategies: ECG dose modulation; Weight-based tube 
voltage; Prospective ECG triggering; Minimization of "padding=; Minimization of Z-axis coverage; 
Limiting of the field of view (FOV); Automatic exposure control.  Coronary CTA performance 
necessitates the use of iodinated contrast.  Minor reactions to x-ray contrast material can occur, including 
itches or hives with an incidence of approximately 1 in 200 subjects. More severe reactions that are very 
infrequent include hypotension, laryngospasm and bronchospasm.  The incidence of these reactions is 
estimated at about 1 in 5,000 and is treated with intravenous epinephrine.  Extravasation of x-ray contrast 
material outside the vein during injection may occur and result in a painful soft tissue swelling and 
bruising.  Subjects will be monitored for extravasation during injection and the amount of contrast material 
injected into the tissues is usually quite small without significant clinical consequences.   
 
 
VIII.B.  Risks of FFRCT analysis 
 
In subjects with Coronary CTA, FFRCT analysis will be performed using the clinically acquired Coronary 
CTA data set.  The FFRCT analysis in these subjects does not require additional imaging, medication or 
radiation exposure.  There is no additional risk to the subject. 
 
 
IX. STUDY PROTOCOL REQUIREMENTS 
 
1. After providing informed consent, each subject will undergo the following assessments as indicated on 
CRF:  
a. Collection of demographic information, including height, weight, presenting symptoms 
and neurologic status. 
b. A summary of index carotid revascularization procedure 
c. A summary of the subject9s relevant medical and surgical history (Diabetes mellitus, 
Dyslipidemia, Arterial hypertension, Smoking) 
d. Recording of concurrent and concomitant medications  
 
2. Coronary CTA (cCTA) Procedure  
.  
1)  Perform cCTA with strict adherence to SCCT guidelines including, but not limited to: 
a. Heart rate control: administration of ³-blockers, if needed, to achieve a heart 
rate of <60 bpm 
b. CT image acquisition after administration of sublingual nitrate spray or after 
administration of sublingual nitrate tablet (3-5 minutes) 
c. using breath-holding and other techniques to minimize motion artifact  
d. contrast protocols: bi-phasic injection protocol 
e. kV/mA settings per ALARA principles. Patients who weigh more than 70kg 
should be scanned at 120kV. 
2) The additional thorax CT findings (pulmonaly oncology, etc.) might be collected at selected 
sites. 

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3. Post-procedure follow up data from clinical visits and/or phone calls 3 months, one and 2 years 
(annually up to 5 years for patients entering prolonged study at participating sites). 
4. Open label randomization will be done after patient screening at approximate rate 1:1 
symptomatic to asymptomatic CAS. 
 
 
X. Case Report Forms  
 
Electronic or paper case report forms will used.  
 
 
XI.  Institutional Review  
 
Before starting this study, the protocol will be submitted to the regulatory bodies/local health authorities 
(in accordance with local regulations) and the study will not start before the EC/IRB gives written approval 
or a favorable opinion in accordance with ICH E6-GCP and all applicable regulatory bodies/local health 
authorities give approval or a favorable opinion as required.  
 
 
XII.  Informed consent  
 
Written and oral information about the study in a language understandable by the subject will be given to 
all subjects by the investigator and/or designee.  The subject9s willingness to participate in the study will 
be documented in writing in a consent form, which will be signed by the subject with the date of that 
signature indicated.  The investigators will keep the original consent forms and copies will be given to the 
subjects. The informed consent will also be signed and dated by the person who conducted the informed 
consent discussion. 
 
XIII  Confidentiality regarding study subjects  
 
The investigator(s) must assure that the privacy of the subjects, including their personal identity and all 
other personal medical information, will be maintained at all times.  In documents or image material 
submitted to the sponsor, subjects will not be identified by their names, but by an identification code. 
Personal medical information may be scrutinized for the purpose of verifying data recorded in the CRF.  
This may be done by properly authorized persons, the quality assurance unit, or regulatory authorities.  
Personal medical information will always be treated as confidential.  
 
 
XIV Financial Disclosure  
 
The investigator(s) (or investigating institution) will provide the sponsor with accurate financial disclosure 
regarding real or potential financial conflicts of interest. 
 
 

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XV  Insurance  
 
As there is no any invasive investigation product been tested, the local site clinical liability insurance will 
be in power to cover malpractice.  
 
 
XVI  Adverse event and serious adverse event reporting  
 
Only endpoints and adverse events (AE) listed in amendment should be repoted according to ICH-GCP 
requrements. A Clinical Adjudication committee will evaluate all Study Endpoints. 
 
 
 
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