The Vertebrobasilar Flow Evaluation and Risk of Transient Ischemic Attack and Stroke (VERiTAS) Study
Conditions: Vertebrobasilar Insufficiency, Ischemic Attack, Transient, Cerebrovascular Disorder, Brain Ischemia, Stroke
Sponsor: University of Illinois at Chicago

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The Vertebrobasilar Flow Evaluation and Risk of 
Transient Ischemic Attack and Stroke 
(VERiTAS) Study 
 
 
 
 
 
 
 
Principal Investigator:  
 
Sepideh Amin-Hanjani, MD, FACS 
 
 
 
 
 
 
 
 
Assistant Professor of Neurosurgery 
University of Illinois at Chicago (UIC) 
 
 
 
 
 
 
Phone: (312) 996-4842 
  
 
 
 
 
 
Fax: (312) 996-9018 
 
 
 
 
 
 
Email: hanjani@uic.edu 
 
 
Co-Investigators: 
 
 
Fady T. Charbel, MD, FACS  
 
 
 
 
 
 
 
 
Philip B. Gorelick, MD, MPH 
 
 
 
 
 
 
Dilip K. Pandey, MD, PhD 
 
 
 
 
 
Sean Ruland, DO 
 
 
 
 
 
Keith R. Thulborn, MD, PhD 
 
Senior Biostatistician:  
 
DeJuran Richardson, PhD 
 
Site Principal Investigators:  
Mitch Elkind, MD 
Jeffrey Kramer, MD 
David S. Liebeskind, MD 
Frank Silver, MD 
Gregory J. Zipfel, MD 
 
 
 
 
 
 
 
 
 
 
 
 
 

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1.1 
STUDY SUMMARY 
 
Objective  
The primary objective of this study is to determine if patients with symptomatic vertebrobasilar 
stenosis or occlusion with compromised intracranial blood flow as demonstrated by magnetic 
resonance (MR) imaging are at increased risk for recurrent stroke compared to patients with 
normal blood flow. 
Study Design 
This is a multicenter prospective observational study. 
 
Study Population 
Patients with symptomatic vertebrobasilar stenosis ( 50%) or occlusion. 
 
Study Evaluations 
Noninvasive magnetic resonance (MR) imaging consisting of quantitative magnetic resonance 
angiography (QMRA) and MR perfusion imaging to assess intracranial blood flow. 
 
Number of Participants 
80 
 
Number of Clinical Sites 
6 
 
Primary Endpoint 
 
Fatal and nonfatal ischemic stroke in the vertebrobasilar territory within 12 months. 
1/21/15 Footnote:  the definition used by the adjudication committee per Dr. Kasner is, “Ischemic stroke 
is defined as new neurological symptoms or signs lasting at least 24 hours or lasting 
less than 24 hours but associated with new infarct on CT or MRI”. 
 
Secondary Endpoints 
 
TIA and fatal and nonfatal ischemic stroke in the vertebrobasilar territory. 
 
Ischemic stroke in any vascular territory. 
 
All ischemic stroke and vascular death. 
 
Aggregate of any ischemic stroke, myocardial infarction and vascular death. 
 
All stroke (ischemic and hemorrhagic). 
 
All death (vascular and nonvascular). 
 
Neurological impairment by NIH Stroke Scale (NIHSS). 
 
Neurological disability by modified Barthel Index (BI). 
 
Handicap by modified Rankin Scale (MRS) and modified Glasgow Outcome Score (GOS). 
Principal Investigator 
Sepideh Amin-Hanjani, MD, FACS 
Assistant Professor of Neurosurgery 
University of Illinois at Chicago 
Data Management  
DeJuran Richardson, PhD 

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Data Management Center, Stroke Center 
University of Illinois at Chicago 

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1.2 
OBJECTIVES 
Primary Objective: 
 
 
To test the hypothesis that among patients with symptomatic vertebrobasilar disease 
(VBD), those with distal blood flow compromise are at higher risk of subsequent 
posterior circulation stroke than those with normal flow.   
 
Secondary Objectives: 
 
 
To determine the correlation between large vessel flow (QMRA) and tissue level 
perfusion (MR perfusion) in the posterior circulation, and the predictive value of each 
modality. 
 
To determine other predictive factors for stroke in this population. 
 
To determine the hemodynamic effects of varying degrees of vertebrobasilar stenosis 
and occlusion. 
 
To determine changes in hemodynamic status of patients on medical therapy over time. 
 
To determine the utility of QMRA as a non-invasive screening and monitoring tool in 
symptomatic vertebrobasilar disease (VBD). 
 
1.3 
BACKGROUND AND RATIONALE 
 
Approximately 700,000 strokes occur annually in the U.S. making it the third leading cause of 
death and the leading cause of permanent disability among adults.  Posterior circulation strokes 
account for 30-40% of all ischemic strokes, resulting in approximately 200,000 cases per year. 
Atherosclerotic disease of the vertebrobasilar system is an important etiology of posterior 
circulation stroke1.   Symptomatic vertebrobasilar disease (VBD) carries a high annual risk of 
stroke, averaging 10-15% per year despite medical therapy. Vertebrobasilar stroke is 
particularly prone to resulting in devastating consequences due to the concentrated ‘eloquence’ 
of brain tissue supplied by the posterior circulation 2.  Consequently, vertebrobasilar stroke can 
result in high rates of death and disability. 
Risks of stroke in VBD 
Several retrospective studies have estimated the risk associated with vertebrobasilar stenosis 
(50-99%) to be 10-15% per year 3-5.  These stroke rates approach those seen with symptomatic 
high grade extracranial carotid stenosis.  In a retrospective study of 44 patients with distal 
vertebral artery (VA) or basilar artery (BA) stenosis of ≥50%, Mouffarij et al. reported a 27% 
incidence of vertebrobasilar ischemic events, with 5 of 12 events being stroke rather than TIA3. 
An overall 80% stroke free survival at 2 years was evident in this study.  A study by Qureshi et 
al. of 102 patients with symptomatic VBD (>50% stenosis) demonstrated that 14% of patients 
experienced recurrent stroke, with a stroke free survival of only 72% at two years5.  
Retrospective analysis from the WASID study group6 examined the risk of stroke in 68 patients 
with symptomatic intracranial vertebrobasilar 50-99% stenosis treated with aspirin or warfarin 
over a median follow-up of 13.8 months.  Fifteen (22%) of the patients suffered stroke, of which 
four (27%) were fatal.  They reported an overall stroke risk of 13.6 to 15 per 100 patient years 
for vertebral and basilar artery stenosis respectively, and 7.8 to10.7 per 100 patient years for 
stroke in the territory of the stenotic artery4.  Data from the prospective WASID trial comparing 
use of warfarin versus aspirin in symptomatic intracranial stenosis of 50-99% in 569 patients 
demonstrated that 15% of patients suffered stroke in the territory of the stenotic artery7.  The 

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incidence of stroke at one year was 12%, with stroke rates that were not significantly different 
between the anterior and posterior circulation8.  In another recent prospective study of patients 
with intracranial stenosis ≥ 50%, ischemic events were reported for the 49 patients of the full 
cohort of 102 patients who harbored symptomatic vertebral or basilar disease.  The frequency of 
recurrent ischemic events (TIA and stroke combined) was found to be 42.8% during a mean 
follow-up of 23.4 months9. 
 
The predominant stroke mechanism for patients with VBD appears to be regional 
hypoperfusion10; although thrombotically active plaques are a prominent feature of symptomatic 
carotid disease, this mechanism appears less prominent as the primary cause of ischemia 
related to vertebrobasilar stenosis.  The posterior circulation vascular anatomy can allow for 
potential compensations to maintain distal arterial territory flow through collaterals (such as the 
posterior communicating arteries) in the setting of proximal vessel stenosis or occlusion.  The 
existence and extent of these compensatory blood flow pathways, therefore, may influence the 
risk of stroke. 
Rationale for use of QMRA and MR Perfusion   
Various imaging techniques exist for assessing cerebrovascular hemodynamic compromise, 
including SPECT, PET, Xenon CT and TCD.  These modalities are generally aimed at 
assessing cerebral tissue perfusion, and have proven valuable in assessment of anterior 
circulation flow compromise.  However, these modalities have been less useful in the posterior 
circulation due to factors such as inadequate spatial resolution for the compact brain territory 
involved, and bony skull base artifacts. An alternative strategy is therefore desirable. 
Measurement of large vessel flow in affected and major collateral vessels in the posterior 
circulation is one such strategy, and can be obtained non-invasively using phase contrast 
QMRA11-14.   QMRA imaging can be easily combined with MR perfusion imaging to provide both 
large vessel and tissue level hemodynamic assessment.  
  
The technique of phase contrast QMRA allows volumetric flow to be measured directly and 
noninvasively in the craniocervical vasculature, and has been shown to be accurate in both the 
in vitro and in vivo setting15-19. Standardized QMRA software is available as NOVA (Noninvasive 
Optimal Vessel Analysis), and has been used extensively to assess patients with 
cerebrovascular disease at the central coordinating site, University of Illinois at Chicago (UIC).  
A retrospective non-blinded cohort study examining outcomes of patients with symptomatic VBD 
demonstrated a significantly higher risk of subsequent stroke in patients with hemodynamic 
impairment as assessed by NOVA QMRA.  Furthermore, QMRA may provide an appropriate 
non-invasive screening and follow-up monitoring tool in patients with known or suspected VBD.  
 
Unlike QMRA which provides information regarding volumetric flow within a given vessel, MR 
perfusion imaging provides characterization of tissue level perfusion in the brain territory of 
interest20.  MR perfusion imaging is readily available on most clinical scanners, and can provide 
information regarding tissue level hemodynamic compromise.  Therefore, tissue perfusion 
measurements may provide important correlative and predictive data for the conductance flow 
data from the large vessels obtained using phase contrast QMRA.  
Rationale for the VERiTAS study 
VBD represents a potentially treatable high risk source of stroke.  Advances in endovascular 
angioplasty and stenting have created new options for the treatment of VBD, but the 
interventions themselves carry significant risks21, 22, and the selection criteria for appropriate 
candidates remains uncertain.  Our preliminary published retrospective data23 suggests that the 

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risk of stroke in VBD is affected by the extent to which intracranial blood flow is compromised. 
Specifically, our analysis has indicated that patients with low intracranial flow as assessed by 
noninvasive QMRA are at significantly higher risk of stroke than those with normal flow.  The 
objective is now to conduct a prospective longitudinal study of patients with symptomatic VBD to 
determine if level of blood flow compromise assessed by QMRA and MR perfusion at the 
baseline examination predicts risk of recurrent ischemic events.    
 
1.4 
STUDY DESIGN  
 
The study is a multi-center prospective cohort study.  Eligible patients will undergo, in addition to 
standard assessments, a QMRA imaging study and MR perfusion study to assess their 
cerebrovascular hemodynamic status, the results of which will be interpreted centrally and kept 
blinded from the clinicians caring for the patient.  
 
The patients will be prospectively followed for a minimum of one year, and a maximum of two 
years, on current standard medical regimen to include standard stroke/cardiovascular risk factor 
modification and medical therapy, and evaluated for recurrent ischemic events.  
 
We anticipate enrollment of a minimum of four patients per year per site over four years with a 
minimum of one-year of follow-up. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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1.5 
STUDY SCHEMA 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
ntional angiogram prior to screening and eligibility will not require repeat angiography if study 
adequate 
Eligible based upon clinical entry criteria 
 Patients with symptomatic vertebrobasilar disease by screening 
imaging modality (CTA, MRA, TCD, Angio) 
SCREENING
ENROLLMENT: Informed consent 
  Blinded QMRA and MR perfusion studies; baseline assessments 
Maximal medical management  
(risk factor modification and medical therapy) 
CTA or conventional angiographic confirmation = 50% stenosis 
(jpeg sent to CCC before enrollment for confirmation) 
BASELINE ASSESSMENT
 
Blinded  QMRA and MR perfusion studies at 6m, 12m (minimum) 
Monthly telephone interviews 
Neurological examination at 6m, 12m (minimum) 
Primary endpoint reached:  
Further intervention per treating 
team 
 No primary endpoint reached:  
Continued follow-up for a 
minimum of 1 year  
 Ascertainment of primary and secondary endpoints 
DATA COLLECTION 
FOLLOW-UP (1 yr minimum) 

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1.6 
ELIGIBILITY CRITERIA 
 
Inclusion Criteria: 
 
 
Symptomatic patients (TIA or stroke) in the vertebrobasilar territory. 
 
Conventional angiography or CT angiography (CTA) demonstration of ≥ 50% stenosis or 
occlusion of extracranial or intracranial vertebrobasilar artery. 
 
jpeg sent to CCC for confirmation prior to enrollment.  
 
Symptoms within 60 days of enrollment.  
 
Age 18 and above.  
 
Able to provide informed consent. 
 
Exclusion Criteria: 
 
1. Neurologic criteria:  
 
Major disabling stroke prohibiting the ability to return for follow-up assessment. 
 
Any neurological disease which would confound follow-up assessment. 
2. Medical criteria: 
 
Any severe co-morbidity condition with less than 12 month life expectancy. 
 
Known cardiac disease associated with cardioembolic risk specifically atrial fibrillation, 
prosthetic valves, endocarditis, left atrial/ventricular thrombus, cardiomyopathy with 
EF<25%, cardiac myxoma. 
 
Blood dyscrasias, specifically polycythemia vera, essential thrombocytosis, sickle cell 
disease. 
3. Disease criteria: 
 
Non-atherosclerotic disease vertebrobasilar disease including dissection, fibromuscular 
dysplasia, vasculitis, radiation induced vasculopathy. 
 
Unilateral vertebral stenosis or occlusion 
4. Patient criteria: 
 
Unable or unwilling to undergo MRI. 
 
Unable to undergo conventional angiography or CT angiography (CTA). 
 
Pregnancy. 
 
Concurrent participation in an interventional trial for treatment of vertebrobasilar disease. 
 
Renal dysfunction will be exclusionary if it precludes angiography. Renal dysfunction will not be 
exclusionary if it precludes gadolinium administration as such patients may be enrolled but will 
not undergo the MR perfusion portion of the study imaging protocol, and thus, will not receive 
gadolinium. No subjects will be excluded based upon gender, race, ethnic group, religion or 
socioeconomic status.  Children will not be recruited, as atherosclerotic VBD is a condition that 
affects adults primarily in later life and is not a disease that occurs or is relevant in children. 
 
1.7 
PATIENT RECRUITMENT AND ENROLLMENT 
 
Patients presenting with vertebrobasilar distribution TIA or stroke are the source group of 
patients.  Diagnostic evaluation of these patients will be performed at the discretion of the 
treating physicians at the participating center, but commonly includes one or more of several 
imaging modalities: magnetic resonance angiography (MRA), computed tomographic 
angiography (CTA), transcranial Doppler (TCD), or conventional angiography.  Those patients 
who demonstrate evidence of ≥ 50% vertebrobasilar stenosis by any of these diagnostic 

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imaging are potentially eligible for the study, and will be reported to the study site coordinator or 
any key research personnel who will assist in consenting.  Patients will be identified through the 
Neurosurgery, Neuroendovascular and Neurology services at the participating centers.  No 
study procedures will take place prior to subject consenting.  
At sites where conventional angiography or CTA is not standard of care, subjects will be asked 
to undergo the informed consent process and sign the consent form prior to determination of 
final eligibility (the consent form will include consent for angiography to determine final 
eligibility).  Subjects who meet angiographic inclusion criteria will continue with the study 
procedures; subjects who do not meet angiographic criteria will be withdrawn from the study.  
This will be outlined in the consent form.  At sites where conventional angiography or CTA is 
routine, subjects will be consented based on presence of inclusive angiographic criteria.  
Patients with angiographically confirmed > 50% vertebrobasilar stenosis who meet the clinical 
entry criteria and sign the consent form will be enrolled.   
 
Enrollment 
Eligible patients who agree to participate in the study will sign written informed consent 
documents, and will be considered enrolled into the study.  As part of the process of informed 
consent the patient will be told the purpose of the study, and that the study entails undergoing 
MR scans, and clinical follow-up to assess for occurrence of stroke and TIA.  Consent will be 
documented by signing a consent form approved by the participating site Institutional Review 
Board (IRB).   At the time of the enrollment, patients will fall into two categories: 
1. Patients who have undergone or are scheduled to undergo conventional catheter 
angiography or CTA performed as part of standard work-up. 
2. Patients for whom conventional catheter angiography or CTA is not considered to be part of 
the standard work-up: the participant is informed of the protocol requirement for catheter 
angiography or CTA at the time of informed consent, and single or bilateral vertebral vessel 
injection conventional angiography, or head and neck CTA, will be performed as part of the 
study.  Any patients not meeting the angiographic criteria of ≥ 50% vertebrobasilar stenosis will 
not continue as participants in the study and will not undergo the study procedures described 
below.  
 
1.8 
STUDY PROCEDURES  
 
Baseline Evaluations 
Clinical Evaluation: 
Following enrollment and confirmation of angiographic stenosis ≥ 50%, baseline assessments 
by the participating study coordinator and study physician are performed.  This will consist of a 
thorough clinical and neurological evaluation including review of recent hospital records, and 
imaging studies.  Clinical information including the nature and frequency of cerebral ischemic 
events will be gathered. Medications at the time of enrollment will be recorded.  Data regarding 
standard stroke risk factors will be specifically recorded including the following baseline history: 
age, gender, race, hypertension, diabetes mellitus, lipid disorder, coronary disease, smoking, 
alcohol consumption, and parental death from stroke.  A neurological evaluation will be 
performed.  The NIHSS will be recorded and functional status will be measured using the 
Barthel Index, modified Rankin Scales and modified Glasgow Outcome Score.  The data will be 
recorded on web-based standardized case report forms.  
 
MR imaging: 
An MR imaging protocol consisting of QMRA and MR perfusion will be performed at time of 
enrollment.  The study is performed based upon a pre-specified protocol utilizing standardized 

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NOVA software.  The NOVA portions of the study will be transferred via secure internet based 
transfer to the clinical coordinating site at UIC for central review by a certified NOVA interpreter. 
The MR perfusion portion of the study will be sent via sFTP transfer or CD to the clinical 
coordinating center at UIC for central review by a specified neuroradiologist.  The results of the 
study will remain blinded to the patient and participating site personnel including the evaluating 
study physician. 
 
The imaging protocol will be performed with the use of NOVA software installed on Siemens, 
G.E. or Phillips 3.0 Tesla MR scanners.  The protocol will involve an approximately 60 minute 
MR scan consisting of initial time of flight (TOF) imaging of the cranial and cervical vasculature 
to include 15 vessels.  A 3-D image of the vessels will be created, based upon which sites for 
blood flow measurement will be marked. Phase contrast MRA imaging will then be performed in 
the plane perpendicular to the identified sites to obtain blood flow measurement at those sites. 
MR perfusion will be performed using the dynamic susceptibility contrast (DSC) technique. 
 
Standard management 
Risk factor modifications 
Patients will be placed on a standard medical regimen to include antithrombotic agents and 
standard stroke/cardiovascular risk factor medical therapy as managed by the participating 
center study physician in conjunction with the patient’s primary care physician.  
 
Follow-up evaluations 
Monthly telephone follow-up assessment 
The participating site study coordinator will contact patients monthly by telephone until 12 
months for determination of new events.  If a potential endpoint is identified treating physician 
will be notified, and the participating site arranges for the patient to be evaluated by the blinded 
study physician within 72 hours.  If a stroke is clinically suspected, brain imaging with CT or MR 
will be performed in accordance with standard clinical management.  The data from the 
telephone interviews will be recorded using standardized web-based case report forms. 
Clinical visit follow-up assessment 
In person follow-up will be performed at the participating site at 6 months (m), and 12m as a 
minimum, and every 6m thereafter up until completion of the study or 2 years maximum.  A 
detailed neurological evaluation and assessment for new symptoms or signs will be performed 
at these visits.  Interval occurrence of any symptoms of cerebrovascular disease or other 
medical problems will be determined.  Clinical evaluations will be performed by the blinded 
study physician unfamiliar with the results of the study MR imaging.  The patient’s medication 
regimen and NIHSS Score will be recorded.  The data will be recorded using standardized web 
based data forms.   
 
MR imaging follow-up assessment 
The MR imaging protocol will be repeated at 6m and 12m, at a minimum, and at 24 months if 
prior to the completion of the study.  Results will be centrally reviewed and the results will 
remain blinded from the participating center. 
 
 
 
 
 
 
 

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Time course of assessments and follow-ups 
MONTHS 
0 1* 2*
3*
4*
5*
6*
7*
8*
9*
10* 11* 12*
18
24
Demographics 
x  
 
 
 
 
 
 
 
 
 
 
 
 
 
Baseline Evaluation 
x  
 
 
 
 
 
 
 
 
 
 
 
 
 
Angiogram/CTA 
x  
 
 
 
 
 
 
 
 
 
 
 
 
 
MR imaging 
x  
 
 
 
 
x 
 
 
 
 
 
x 
 
x 
Telephone interview 
 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
 
Clinical Follow-up 
Evaluation 
x  
 
 
 
 
x 
 
 
 
 
 
x 
x 
x 
NIHSS, BI, MRS, GOS 
x  
 
 
 
 
x 
 
 
 
 
 
x 
x 
x 
  *Minimum follow-up for all recruited patients (12m). Maximum is 24m.   
 
1.9 
STUDY ENDPOINTS 
 
Primary endpoint: 
 
Stroke (fatal and nonfatal ischemic stroke) in the vertebrobasilar territory at 12 months. 
 
Secondary endpoints: 
 
TIA and fatal and nonfatal ischemic stroke in the vertebrobasilar territory. 
 
Ischemic stroke in any vascular territory. 
 
All ischemic stroke and vascular death. 
 
The aggregate of ischemic stroke, myocardial infarction and vascular death. 
 
All stroke (ischemic and hemorrhagic). 
 
All death (vascular and nonvascular). 
 
Neurological impairment as determined by the NIH Stroke Scale. 
 
Neurological disability as determined by the modified Barthel Index. 
 
Handicap as determined by the modified Rankin Scale and Glasgow Outcome Score. 
 
Ischemic stroke is defined as new neurological symptoms or signs lasting at least 24 hours or 
lasting less than 24 hours but associated with new infarct on CT or MRI.  TIA is defined as new 
neurological symptoms or signs lasting less than 24 hours without radiographic correlate of 
infarct.  Vascular death is defined as a death of known vascular etiology or sudden death that 
could not be explained by a known nonvascular process.  
Initial determination of endpoints will be defined by the participating site study physician but will 
be ultimately be independently determined by a central adjudication committee.   
 
1.10 DATA ANALYSIS 
 
A dedicated Biostatistician and Director of the Data Management Center for the Center for 
Stroke Research at the UIC Department of Neurology and Rehabilitation, UIC will oversee all 
statistical analysis of the study. 
 
Analysis 
Analysis of the primary endpoint (ischemic stroke in the vertebrobasilar territory) will consist of 
time-to-endpoint comparison using the log-rank test between patients designated as ‘low flow’ 
versus ‘normal flow’.  The designation of flow status will be based upon the patient’s initial 
enrollment QMRA study, using parameters defined in the preliminary studies.  Adjusted analysis 
will be performed using multivariate logistic and proportional hazard regression models to 
examine stroke incidence adjusted for key confounders.  Post-hoc sensitivity analysis will be 

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performed to examine alternative cut-points for designation of low or normal flow status, and to 
examine the predictive value of each MR imaging modalities (QMRA and MR perfusion) and 
whether the combination of the two modalities provides a better indicator of stroke risk than 
either alone.  Patients will be censored from analysis at the time of any crossovers to 
interventional procedures.  
 
Sample size calculations  
Sample size estimates are based upon stroke rates from published preliminary data23, which 
indicate a 71% and 100% one year stroke free survival in the ‘low flow’ and ‘normal flow’ 
groups, respectively, translating into annual event rates of 0.29 and 0.0.  Although our data 
indicated a 0 stroke rate in the ‘normal’ flow group, there was a 0.04 rate of TIA, which can 
occur on a clinical spectrum with stroke.  As a result the sample size calculations were based on 
a conservative estimate of 0.02 event rate in the normal flow group.  Sample sizes were 
calculated for a range of possible event rates in the low flow group from 0.18 to 0.28.  A 10% 
attrition rate was included in the calculations.  Based upon these estimates, a total sample size 
of 80 patients will achieve approximately 80% power in detecting a significant difference 
between the groups with an annual event rate of 0.22 in the low flow group.  Exploration for risk 
factors and adjustment for covariates will be performed with Cox proportional hazards analysis. 
 
1.11 RISKS 
 
Potential Risks to Subjects: 
For patients who would not have undergone conventional cerebral angiogram or CTA as part of 
their standard work-up, the risk of conventional cerebral angiography or CTA are introduced by 
participation in the study.  In the current era, conventional cerebral angiography poses a 
minimal risk of adverse events, with stroke risk of <1% 24, and these risks will be included in the 
informed consent process. CTA, as an alternative to conventional angiography, also poses 
minimal risk of adverse events.  As part of the study assessments, patients will be undergoing 
MR imaging including MR perfusion with gadolinium contrast.  Patients with contraindication to 
undergoing MRI will be excluded from the study; patients with contraindication to administration 
of gadolinium will not undergo the MR perfusion portion of the imaging protocol, and will not 
receive gadolinium. Therefore the risks related to undergoing MRI are minimal.  There is also a 
potential risk for loss of confidentiality of protected health information (PHI). 
 
Conventional Angiogram: 
The risks associated with angiography are discomfort and bruising in the groin where the 
catheter is inserted into the artery.  The major risk of angiogram is stroke. Some strokes are 
minor and some can lead to death or permanent loss of the ability to see, speak, or move.  The 
risk of stroke associated with angiogram is 1%.  Other less serious risks include bleeding, or 
infection at site of insertion and allergic reaction or kidney damage from the contrast media 
utilized. 
 
CTA: 
The risks include slight risk of bruising or infection where IV is inserted for administration of 
contrast dye, and allergic reaction or kidney damage from the contrast dye utilized. 
 
MRI: 
Some subjects may experience claustrophobia as a result of being put into the MRI machine. 
Subjects who have history of claustrophobia will be informed of description of the procedure. 
MRI is also contraindicated for subjects with metal fragments in the body, pacemakers and 

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aneurysms clips.  All subjects will be screened prior to procedure to ensure there are no 
contraindications.  
 
Risks involved in contrast dye administration are the potential risks of allergic reaction to 
contrast dye, nausea, headache, hot flashes, heart palpitations, rash, hives, slight risk of 
infection where IV is inserted, discomfort at the injection site, difficulty breathing, and in extreme 
cases, death.   
 
Protection Against Risks 
Due to fact that the majority of the procedures to be performed are routinely employed standard 
procedures, the procedural risks will be controlled by performing all procedures according to 
standard of care guidelines.  Protection against the loss of confidentiality will be controlled by 
the use of a secure web based data entry system that is CFR 21 compliant.  Data forms will be 
coded to exclude any patient identifiers.  A master list of subjects linking them to their study 
number will be kept in locked office of the research personnel in a locked cabinet.  Subjects will 
be thoroughly screened to minimize risk of angiography and MRI. 
 
Data and Safety Monitoring 
This study does not include any specified intervention or incorporate any experimental 
treatment.  Given there is no proposed intervention or proposed management beyond standard 
clinical care as defined by the physicians caring for the patient, a Data Safety and Monitoring 
Board is not indicated.  The principal investigator will be responsible for monitoring any adverse 
events related to obtaining angiograms or MRA scans obtained primarily for the purposes of the 
study.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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1.12 REFERENCES 
 
1. 
Caplan LR. Vertebrobasilar disease. Advances in Neurology. 2003;92:131-140. 
2. 
Savitz SI, Caplan LR. Vertebrobasilar disease. N Engl J Med. Jun 23 
2005;352(25):2618-2626. 
3. 
Moufarrij NA, Little JR, Furlan AJ, Leatherman JR, Williams GW. Basilar and distal 
vertebral artery stenosis: long-term follow-up. Stroke. Sep-Oct 1986;17(5):938-942. 
4. 
Prognosis of patients with symptomatic vertebral or basilar artery stenosis. The 
Warfarin-Aspirin Symptomatic Intracranial Disease (WASID) Study Group. Stroke. Jul 
1998;29(7):1389-1392. 
5. 
Qureshi AI, Ziai WC, Yahia AM, et al. Stroke-free survival and its determinants in 
patients with symptomatic vertebrobasilar stenosis: a multicenter study. Neurosurgery. 
May 2003;52(5):1033-1039; discussion 1039-1040. 
6. 
Anonymous. Prognosis of patients with symptomatic vertebral or basilar artery stenosis. 
The Warfarin-Aspirin Symptomatic Intracranial Disease (WASID) Study Group. Stroke. 
Jul 1998;29(7):1389-1392. 
7. 
Chimowitz MI, Lynn MJ, Howlett-Smith H, et al. Comparison of warfarin and aspirin for 
symptomatic intracranial arterial stenosis. N Engl J Med. Mar 31 2005;352(13):1305-
1316. 
8. 
Kasner SE, Chimowitz MI, Lynn MJ, et al. Predictors of ischemic stroke in the territory of 
a symptomatic intracranial arterial stenosis. Circulation. Jan 31 2006;113(4):555-563. 
9. 
Mazighi M, Tanasescu R, Ducrocq X, et al. Prospective study of symptomatic 
atherothrombotic intracranial stenoses: the GESICA study. Neurology. Apr 25 
2006;66(8):1187-1191. 
10. 
Voetsch B, DeWitt LD, Pessin MS, Caplan LR. Basilar artery occlusive disease in the 
New England Medical Center Posterior Circulation Registry. Arch Neurol. Apr 
2004;61(4):496-504. 
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