The Occurrence of Abdominal Aortic Aneurysms in Patients With Ruptured Intracranial Aneurysms
Conditions: Aneurysm Abdominal, Cerebral Aneurysm Ruptured
Sponsor: Leiden University Medical Center

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RESEARCH PROTOCOL 
 
 ‘’The occurrence of abdominal aortic aneurysms in patients with ruptured intracranial 
aneurysms’’ 
A.L. Hamming1,2, W.A. Moojen3, J. Van Schaik2, J.R. van der Vorst2, W.C. Peul3, A. 
Schepers2, J.J.W.M. Brouwers2 
 
1Department of Surgery, Haaglanden Medical Centre, The Hague, The Netherlands 
2 Department of Vascular Surgery, Leiden University Medical Centre, Leiden, The 
Netherlands 
3 Department of Neurosurgery, University Neurosurgical Centre Holland, Leiden & The 
Hague, The Netherlands 
 
 
 
 
Protocol ID 
NL-009714 
Short title 
Occurrence of AAA in aSAH patients  
Version 
 
1.3 
Date 
18-11-2025 
Coordinating investigator 
 
A.L. Hamming (MD) 
Principal investigator 
J.J.W.M. Brouwers (MD, PhD) 
Research team 
 
 
 
 
 
 
 
 
 
Dr. J.J.W.M. Brouwers  
 
Drs. A.L. Hamming 
 
Dr. A. Schepers 
 
Dr. J. Van Schaik 
 
Dr. J.R. van der Vorst 
 
Dr. W.A. Moojen 

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 
Prof. dr. W.C. Peul 
Sponsor  
Leiden University Medical Centre (LUMC) 
Albinusdreef 2, 2333 ZG Leiden  
 
Subsidising party 
Aneurysmafonds 
Jacobus Stichting 
Independent expert 
Prof. dr. Vahrmeijer 
Molecular guided precision surgery 
LUMC, The Netherlands 
Laboratory sites  
Abdominal Ultrasonography Centres, The 
Netherlands 
Pharmacy  
Not applicable 
 

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PROTOCOL SIGNATURE SHEET 
 
Name 
Signature 
Date 
Head of Department:  
Dr. A. Schepers 
 
 
 
14-08-2025 
Principal Investigator:  
Dr. J.J.W.M. Brouwers 
 
 
 
14-08-2025 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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TABLE OF CONTENTS  
1.INTRODUCTION AND RATIONALE................................................................................... 9 
2.OBJECTIVES ....................................................................................................................11 
3.STUDY DESIGN ...............................................................................................................12 
3.1Study design ................................................................................................................12 
4.3.2 Study sites ...................................................................................................................12 
5.STUDY POPULATION ......................................................................................................13 
5.1Population ....................................................................................................................13 
5.2Inclusion criteria ...........................................................................................................13 
5.3Exclusion criteria ..........................................................................................................13 
5.4Sample size calculation ................................................................................................14 
6.TREATMENT OF RESEARCH PARTICIPANTS ...............................................................14 
7.INVESTIGATIONAL PRODUCT ........................................................................................14 
8.NON-INVESTIGATIONAL PRODUCT ...............................................................................14 
9.METHODS ........................................................................................................................14 
9.1Main study parameter/endpoint ....................................................................................14 
9.2Secondary study parameters/endpoint .........................................................................14 
9.3Randomisation, blinding and treatment allocation ........................................................14 
9.4Study procedures .........................................................................................................14 
9.5Timing of data acquisition ............................................................................................15 
9.6Withdrawal of individual research participants ..............................................................15 
9.7Premature termination of the study ..............................................................................15 
10.SAFETY REPORTING ....................................................................................................15 
10.1Temporary halt for reasons of research participant safety ..........................................15 
10.2AEs, SAEs .................................................................................................................16 
10.2.1AAdverse events (AEs)........................................................................................16 
10.2.2SSerious adverse events (SAEs) .........................................................................16 
10.3Follow-up of adverse events ......................................................................................16 
10.4Data Safety Monitoring Board ....................................................................................16 
11.STATISTICAL ANALYSIS ...............................................................................................17 
12.ETHICAL CONSIDERATIONS ........................................................................................17 
12.1Regulation statement .................................................................................................17 
12.2Recruitment and consent ...........................................................................................17 
12.3Compensation for injury .............................................................................................17 
13.ADMINISTRATIVE ASPECTS, MONITORING AND PUBLICATION ...............................18 
13.1Handling and storage of data and documents ............................................................18 
13.2Monitoring and Quality Assurance..............................................................................18 
13.3Amendments ..............................................................................................................18 
13.4Annual progress report ...............................................................................................18 
13.5Temporary halt and (prematurely) end of study report ................................................18 
13.6Public disclosure and publication policy .....................................................................19 
14.STRUCTURED RISK ANALYSIS ....................................................................................19 

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15.REFERENCES ................................................................................................................19 
 
 
 
 
 
 
 
 
 
 

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LIST OF ABBREVIATIONS AND RELEVANT DEFINITIONS  
 
 
PAA 
Popliteal Artery Aneurysm 
AAA 
Abdominal Aortic Aneurysm 
AA 
Aortic Aneurysm 
CoA 
Coarctation of Aorta 
BAV 
Bicuspid Aortic Valve 
IA 
Intracranial Aneurysm 
aSAH 
Aneurysmal Subarachnoid Haemorrhage  
LUMC 
Leiden University Medical Centre  
SPARTA 
Study on Prognosis of Acutely RupTured Aneurysms 
US 
Ultrasound Duplex 
AE 
Adverse Event 
CCMO 
Central Committee on Research Involving Human Subjects; in Dutch: 
Centrale Commissie Mensgebonden Onderzoek 
DSMB 
Data Safety Monitoring Board 
GCP 
Good Clinical Practice 
GDPR 
General Data Protection Regulation; in Dutch: Algemene Verordening 
Gegevensbescherming (AVG) 
IB 
Investigator’s Brochure 
IC 
Informed Consent 
IMDD 
Investigational Medical Device Dossier  
METC  
Medical research ethics committee (MREC); in Dutch: medisch-ethische 
toetsingscommissie (METC) 
Review 
committee 
Medical research ethics committee (MREC) or CCMO 
 
(S)AE 
(Serious) Adverse Event 
Sponsor 
The sponsor is the party that commissions the organisation or 
performance of the research, for example a pharmaceutical 
company, academic hospital, scientific organisation or investigator. A 
party that provides funding for a study but does not commission it is 
not regarded as the sponsor, but referred to as a subsidising party. 
UAVG 
Dutch Act on Implementation of the General Data Protection 
Regulation; in Dutch: Uitvoeringswet AVG 
 
 

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WMO 
Medical Research Involving Human Subjects Act; in Dutch: Wet 
Medisch-wetenschappelijk Onderzoek met Mensen 

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SUMMARY 
 
Rationale: Aneurysms of different types are known to be associated. In literature, 
concomitant concurrence of intracranial- and aortic aneurysms is described. Screening for 
aortic aneurysms in patients with intracranial aneurysms or aneurysmal subarachnoid 
haemorrhage could be cost-effective and of significant importance to decrease morbidity and 
mortality. The available literature on the association between the two types of aneurysms is 
sparse and in general of poor methodological quality. This protocol presents a study to more 
adequately evaluate the association between intracranial- and aortic aneurysms. 
 
Objective: To investigate the occurrence of abdominal aortic aneurysms in patients who 
experienced aneurysmal subarachnoid haemorrhage. 
 
Study design: This prospective cohort study by collaboration of multiple neurovascular 
centres in the Netherlands will include patients who experienced aneurysmal subarachnoid 
haemorrhage. The study participants will receive an abdominal ultrasound of the aorta to 
detect an aneurysm.  
 
Study population: Aneurysmal subarachnoid haemorrhage patients from another 
prospective cohort trial in the Netherlands. 
 
Main study parameters/endpoints: The primary outcome, is the occurrence of abdominal 
aortic aneurysms in the here above described study population, detected on abdominal 
ultrasound. 
 
Nature and extent of the burden and risks associated with participation, benefit and 
group relatedness: Patients will not receive an intervention, but only a diagnostic imaging 
without radiation exposure. The burden associated with this study is considered minimal and 
the risks negligible. An abdominal ultrasound is a non-invasive diagnostic method with no 
risks for the participant. The only possible burden to the participant is travel and appointment 
time with a risk of detecting an abdominal aortic aneurysm or other (occult) intra-abdominal 
pathologies. When an aneurysm, sub-aneurysm or other intra-abdominal pathology is 
detected, surveillance or treatment according to standard of care and guidelines will be 
offered. 
 
 
 
 
 
 
 
 
 
 

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1. INTRODUCTION AND RATIONALE 
 
Aneurysms at different anatomical locations are known to be associated with one another 
and could co-exist (1-3).  For example, former research found popliteal artery aneurysms 
(PAA) and abdominal aortic aneurysms (AAA) to be highly associated, with a co-prevalence 
of 20-30%(1, 4, 5). Consequently, health care guidelines recommend screening for 
abdominal aortic aneurysm (AAA) when a popliteal artery aneurysm (PAA) is detected, and 
vice versa(4). Furthermore, coarctation of the aorta (CoA) and bicuspid aortic valve (BAV) 
seem to be associated with intracranial aneurysms (IA)(6-8). Due to known associations 
between different aneurysm locations and the increased prevalence of IA in other aortic 
pathology, IAs are also suggested to be associated with different types of aortic aneurysms 
(AA)(3, 9).  
 
Early detection of IAs and AAs is of importance for the prevention of rupture. 
Aneurysm rupture leads to a major health risk with very high morbidity and mortality(10, 11). 
Rupture of an AA leads to major intra-thoracic or intra-abdominal bleeding dependent on the 
type, whereas an IA rupture causes a subarachnoid haemorrhage (aSAH) with a high 30-day 
mortality and a high risk of neurological complications(12-14). To prevent these severe 
complications, screening IA patients for AAs or vice versa could be of great relevance.  
 
The available literature on the association between these types of aneurysms is very 
sparse and of overall low methodological quality(3). For the most part, retrospective- and 
cross-sectional studies were performed on the question whether IA and AA are 
associated(15-23). These studies were of low- to moderate methodological quality and with a 
high variability in IA-AA co-occurrence results. A prospective cohort study from Japan 
however, which included 181 IA patients, found an AAA-occurrence of 7.2% by 
ultrasonography(24). Another prospective cohort study from the United States of America 
found an occurrence of 12% among a study 81 aSAH patients, using ultrasonography as 
well(25). These occurrence rates are evidently higher compared to the general adult 
population (0.92-1.31%) and in the male population of 60 years and older (3%)(26, 27). 
Beside the two mentioned prospective cohort studies in Japan and the United States, 
research on this subject in the European population is lacking. 
 
Screening for an AAA in IA patients could be favourable for preventing aneurysm 
rupture. This could lead to less morbidity and mortality, hospital admissions and overall 
health-care costs. Due to the limited evidence about this subject, it is not yet clear if 
screening IA patients for AA has a role in daily clinical practice. Earlier research suggests 
that patients with an IA could be cost-effectively screened for an AAA by abdominal 
ultrasound (US). Screening for other types of AA or IA in patients with AA is currently thought 
not favourable, because of the need for other high-cost imaging modalities. The aim of this 
prospective cohort study is to investigate the occurrence of AAA in patients who have 
experienced aSAH.  
 
 
 
 

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2. OBJECTIVES 
 
Primary Objective: to evaluate the occurrence rate of abdominal aortic aneurysms (AAA) in 
patients diagnosed with an aneurysmal subarachnoid haemorrhage (aSAH). 
 
Secondary Objective: to detect possible risk factors for the occurrence of AAA in patients 
who were diagnosed with aSAH. 
 
 
 
 
 
 
 
 
 
 

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3. STUDY DESIGN 
 
3.1 Study design 
This study will be a prospective cohort study by multiple collaborating centres in the 
Netherlands. 
 
During the period of the study, all aSAH patients (from another prospective cohort trial) will 
be screened for inclusion eligibility. Eligible patients will be included as subjects in this study. 
Study subjects will receive an abdominal US focused on the abdominal aorta. Detecting an 
AAA on abdominal US will result in the daily standard of care for AAA, including surveillance 
and possible treatment by medication, intervention or surgery.  
 
4. 3.2 Study sites 
This study will be conducted by the Department of Surgery in the main study location 
University Medical Center Leiden (LUMC) in collaboration with University Neurosurgical 
Center Holland (UNCH). Eligibility screening and inclusion will be performed by the LUMC. 
 
To answer the research questions of this study, one abdominal US to measure the diameter 
of the aorta will be performed on the included patients.  
 
3.3 Number of study subjects 
We will include 233 subjects as one single cohort. In this study, the collected data and 
analysis will be compared to the general- and at-risk population. 
 
3.4 Study duration 
During an initial period of 6 months, patients will be included as study subjects. Inclusion 
stops when the targeted number of study subjects (N=233) is reached. The study duration is 
expected to be around 1.5 years and the study period will end when all 233 study subjects 
had an abdominal US, or were excluded from the study during the study period for particular 
reasons.  
 
 
5. STUDY POPULATION 
5.1 Population   
All aSAH patients from another large prospective cohort trial in the Netherlands will be 
screened for eligibility(12). The Study on Prognosis of Acutely RupTured Aneurysms 
(SPARTA) is an observational prospective cohort trial conducted in the Netherlands in 
several neurovasculair centres. The aim of this study was to evaluate the long-term clinical 
outcome of aSAH patients who underwent neurosurgical- or endovascular treatment for their 
ruptured IA. The study has a population of around 900 patients. Because of the high risk of 
morbidity following aSAH, a large proportion of this study population will be diseased or 
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5.2 Inclusion criteria 
Patients with a modified Ranking Scale (mRS) of 0-2 will be screened for inclusion eligibility 
in this study(28). This patient group will have the most potential benefit when an AAA is 
detected, due to being still functionally and cognitively independent and longer survival. 
Since patients with an mRS of 3 also have a relatively good outcome compared to patients 
with an mRS of 4-6, these patients might be included as well. Patients with an mRS of 4 until 
6 are severely impaired in their functional and cognitive performance and therefore highly 
dependant on medical care after aSAH. Furthermore, mRS of 6 means that the patient is 
deceased. In terms of already existing morbidity and mortality in this proportion of the aSAH 
patient population, inclusion of those patients would be less relevant for this study aim.  
 
 
In order to be eligible to participate in this study, a participant must meet all of the following 
criteria: 
 
Patient is a study subject of the already existing trial: Study on Prognosis of 
Acutely RupTured Aneurysms (SPARTA)(12) 
 
Inclusion at least one year after aSAH 
 
Written informed consent 
 
By being a study subject of the SPARTA trial, the following criteria are applicable: 
 
Confirmed diagnosis of SAH on CT-scan or lumbar puncture (in the presence of a 
negative CT-scan) 
 
IA related SAH as confirmed with radiological imaging 
 
Age 18 years or older at presentation 
 
Written informed consent for the SPARTA-trial 
 
5.3 Exclusion criteria 
A potential participant who meets any of the following criteria will be excluded from 
participation in this study: 
 
Patient has Loeys-Dietz-, Marfan- or Ehlers-Danlos syndrome 
 
Patients with an mRS of 4 until 6 
 
5.4 Sample size calculation 
Calculation of sample size was performed by using the population-wide prevalence rates of 
AAA in IA patients. The occurrence rate of AAA will be determined in the study population of 
this study.  
 
As formerly described, in the general population, a prevalence of 0.9% for AAA has been 
found. The prevalence of AAA in the at-risk group (men over 60) varies across earlier studies 
but is most often reported between 2 and 3%. For this study, the upper bound - a prevalence 
of 3% - was assumed in the ‘known population’ for comparison.  
 
The population of this study is expected to be comparable to study populations of other 
prospective studies on this matter, which report a high occurrence rate of 7–12% for AAA.  
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represents the lower bound of the anticipated occurrence rate. Using these assumptions in a 
single-group design to obtain a two-sided 95% confidence interval, we require a sample size 
of 233 patients.  
6. TREATMENT OF RESEARCH PARTICIPANTS 
Not applicable, since no treatment will be performed in this study. 
 
7. INVESTIGATIONAL PRODUCT  
Not applicable, since no product will be tested in this study. 
  
8. NON-INVESTIGATIONAL PRODUCT 
Not applicable. 
 
9. METHODS 
9.1 Main study parameter/endpoint 
The primary endpoint of this study will be the occurrence rate of AAA in the study population. 
This occurrence rate will be calculated as the proportion of all performed US in the study 
group (N; %).  
9.2 Secondary study parameters/endpoint 
As a secondary endpoint, we will evaluate risk factors of having an AAA as an aSAH patient. 
Presence of these factors (i.e. smoking, aneurysmal disease in medical history, age, gender) 
will be calculated as the proportion of the total study population (N; %).  
 
9.3 Randomisation, blinding and treatment allocation 
Not applicable in this study, since this will be a prospective single-cohort study using 
diagnostics and no treatment modalities.  
 
9.4 Study procedures 
The study procedures will be performed at LUMC. Informed consent will be obtained from the 
coordinating- and local investigator. When informed consent is obtained from the patient, 
inclusion starts and the study subject will be invited for an US examination of the abdominal 
aorta. 
 
The abdominal US will be performed 1 year after aSAH. The examination will be performed 
by experienced ultrasonographists. The abdominal aorta in a study subject will be defined as 
AAA when having a diameter of 30 millimetres or more is measured. The region in which the 
abdominal aorta will be measured is from the celiac trunk until the aortic bifurcation.  
 
Detailed data from the US examinations (including aneurysm diameter, morphology and 
specified location) will be collected and stored in an electronic data centre (Castor EDC). 
Additional data, including medical history, gender, and more, will be collected as well.  
 

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Data analysis will be centralized and performed by the coordinating investigators of this 
study. 
 
Nota Bene: when an AAA is detected on abdominal US, this needs to result in the current 
standard of care for AAA. The study subject will receive a letter about the findings of the US, 
which will be sent to their general practitioner. A referral to a vascular surgeon can 
consequently be made. When a sub-aneurysm is found, defined as the aorta having a 
diameter of 25-29 millimeters, this will result in a letter to the general practitioner as well with 
an advised follow-up by US every 5 years. This is according to the guidelines of the 
European Society of Vascular Surgery (ESVS)(29).   
 
9.5 Timing of data acquisition  
Baseline 
- 
Informed consent form 
- 
Baseline information Case Report Form (CRF) 
- 
Baseline information includes relevant medical history, medication, smoking. 
 
Ultrasound Centre 
- 
Diameter measurement of the abdominal aorta 
- 
Location of the aneurysm (i.e. suprarenal, juxtarenal or infrarenal) 
- 
Morphology of the aneurysm (i.e. saccular or fusiform)  
- 
Involvement of the mesenteric-, renal-, lumbar- or iliac arteries 
 
9.6 Withdrawal of individual research participants 
Participants can leave the study at any time for any reason without any consequences if they 
wish to do so. The investigator can decide to withdraw a participant from the study for urgent 
medical reasons. 
9.7 Premature termination of the study 
This is not applicable since there are no significant risks for the patients, which could lead to 
such termination of this study.  
 
 
10. SAFETY REPORTING 
10.1 Temporary halt for reasons of research participant safety 
In accordance to section 10, subsection 4, of the WMO, the sponsor will suspend the study if 
there is sufficient ground that continuation of the study will jeopardise participant health or 
safety. The sponsor will notify the review committee without undue delay of a temporary halt 
including the reason for such an action. It is noted that such is not to be expected form this 
study, as has been explained in paragraph 9.6. 
  

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10.2 AEs, SAEs  
10.2.1 
Adverse events (AEs) 
Adverse events are defined as any undesirable experience occurring to a participant during 
the study, whether or not considered related to examination. The study subjects will undergo 
merely one US during this study, which is a non-invasive imaging modality. However, it is 
crucial to warrant the safety of the study subjects. Therefore, the adverse events reported by 
the participant or observed by the investigator or his staff only during the abdominal US 
examination of this study will be recorded. The same will apply for SAEs, described in 
paragraph 10.2.2. 
10.2.2 
Serious adverse events (SAEs) 
A serious adverse event is any untoward medical occurrence or effect that  
- 
results in death; 
- 
is life threatening (at the time of the event); 
- 
requires hospitalisation or prolongation of existing inpatients’ hospitalisation; 
- 
results in persistent or significant disability or incapacity; 
- 
is a congenital anomaly or birth defect; or 
- 
any other important medical event that did not result in any of the outcomes listed 
above due to medical or surgical intervention but could have been based upon 
appropriate judgement by the investigator. 
An elective hospital admission will not be considered as a serious adverse event. 
 
The sponsor will only report the SAEs during the US examination. These reports will be sent 
through the web portal Research Portal to the review committee that approved the protocol, 
within 7 days of first knowledge for SAEs that result in death or are life threatening followed 
by a period of maximum 8 days to complete the initial preliminary report.  
 
10.3 Follow-up of adverse events 
All AEs will be followed until they have abated, or until a stable situation has been reached. 
Depending on the event, follow up may require additional tests or medical procedures as 
indicated, and/or referral to the general physician or a medical specialist. 
SAEs will be reported till end of study. 
       
10.4 Data Safety Monitoring Board  
As has been previously explained in this study protocol, no risk in safety of the study subjects 
is expected. The actions on the study subjects consist solely of one abdominal US, which is 
a non-invasive imaging procedure. Therefore, no Data Safety Monitoring Board or Safety 
Committee is needed for this study. 
 
11. STATISTICAL ANALYSIS 
Data analyses are primarily descriptive. Categorical variables are reported as frequency (N) 
and percentage (%). Continuous variables are  reported as mean and standard deviation or 

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median and interquartile range (IQR), based on the normality of the distribution. For 
categorical variables, odds ratios will be calculated with corresponding 95% confidence 
intervals. For continuous variables, the mean difference is calculated with corresponding 
95% confidence interval. Statistical comparisons are performed with χ2 test or Fisher’s exact 
test for categorical variables and Student’s t-test or the Mann-Whitney U test for continuous 
variables. 
 
Men of age more than 65 years old are known to have a higher risk of developing an AAA 
compared to other groups. Therefore, a possible subgroup analysis will be performed in 
comparison to other patients.  
 
To identify independent predictors for having an AAA as aSAH patient, multivariate analyses 
through binary logistic regression models with corresponding 95% confidence intervals will 
be performed. Possible confounders of the relation between aSAH and AAA (i.e. age, history 
of hypertension, smoking, sex) are added as covariates.   
Analysis will be performed in R and in the Statistical Package for the Social Sciences (SPSS) 
version 21. A p-value < 0.05 will be considered statistically significant. 
 
12. ETHICAL CONSIDERATIONS 
12.1 Regulation statement 
This study will be conducted according to the principles of the Declaration of Helsinki and in 
accordance with the Medical Research Involving Human Subjects Act (WMO). 
12.2 Recruitment and consent 
Patients form the SPARTA-trial will be asked to participate in this study one year after aSAH 
and will be informed of the study procedures and possible risks. When informed consent is 
obtained, data collection will start and an abdominal US will be performed. 
 
Written informed consent will be obtained from the patient. Information about the study will 
be given both verbally and in writing. After a pre-specified time for consideration, the 
informed consent form will be signed by the patient and the investigator.  
 
When a study subject withdraws from their consent for the study before the abdominal US is 
obtained, no data will be used. When the US has already been obtained, then all data up to 
the moment the study subject withdrew consent will be used for analysis.  
 
12.3 Compensation for injury 
The investigators have asked for exemption for an insurance for research subjects and 
compensation for injury, since only one abdominal US will be performed and for the rest no 
other actions are applied to the study subjects. There exist no risk of injury or death in 
performing an abdominal US.  
 

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13. ADMINISTRATIVE ASPECTS, MONITORING AND PU-
BLICATION 
13.1 Handling and storage of data and documents 
All data will be treated confidentially, coded and will be registered on data registration forms. 
Data management will be handled at the Division Vascular Surgery of Leiden University 
Medical Center. Data will be stored in an electronic data capture and management system. 
Imaging data from the performed US will be stored separately in a picture archiving and 
communication system at the main study centre. A list that contains the study participant and 
associated study identification code will be used to identify an individual study participant if 
necessary. This identification code will not be based on the participants initials or date of 
birth. The list that links the study identification code to the study participants will be kept on a 
designated partition on the hard drive of the research centre. This part will be protected by a 
password. People who have access to this partition are local researchers and quality monitor 
appointed by the principal investigator. These procedures comply with the European law: 
Algemene verordening gegevensbescherming (AVG). All raw data will be collected and 
stored at the main study site, including the trial master file, investigator site file, informed 
consent forms, study data and imaging data. The acquired data will be stored for 15 years 
after the study is finished and will be used for further research if the participant has provided 
consent for the data to be used in further studies. 
  
13.2 Monitoring and Quality Assurance  
Data monitoring and quality assurance will be handled by the Directorate of Quality and 
Patient safety (DKP) at LUMC. Study monitoring will be performed once during the expected 
study period of 1.5 years. We will monitor the informed consent forms, the investigator site 
file and the trial master file, as well as the collected data from the CRF and the abdominal 
US. 
 
13.3 Amendments  
Amendments are changes made to the research after a favourable opinion by the review 
committee has been given. All amendments will be notified to the review committee that gave 
a favourable opinion.  
Non-substantial amendments will not be notified to the review committee, but will be 
recorded and filed by the sponsor.  
 
13.4 Annual progress report 
The sponsor/investigator will submit one summary of the progress of the trial to the review 
committee after one year. Information will be provided on the date of inclusion of the first 
participant, numbers of participants included and numbers of participants that have 
completed the trial, serious adverse events, other problems, and amendments. No more 
progress reports will be made, since the total study duration is expected to be 1.5-2 years.  
 
13.5 Temporary halt and (prematurely) end of study report 
The investigator/sponsor will notify the review committee of the end of the study within a 
period of 8 weeks. The end of the study is defined as the last patient who underwent his or 
her ultrasound duplex.  

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The sponsor will notify the review committee immediately of a temporary halt of the study, 
including the reason of such an action.  
In case the study is ended prematurely, the sponsor will notify the review committee within 
15 days, including the reasons for the premature termination. 
Within two years after the end of the study, the investigator/sponsor will submit a final study 
report with the results of the study, including any publications/abstracts of the study, to the 
review committee.  
 
13.6 Public disclosure and publication policy 
This study protocol will be published online, and the study will be registered in an online trial 
register. After data analysis, these will be published in a peer-reviewed journal. All 
publications using data generated by this study should be discussed and agreed upon by the 
investigators and sponsor.  
 
14. STRUCTURED RISK ANALYSIS  
Not applicable.  
 
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