Clinical trial NCT01932671: The SMART-ORACLE Study
Official title: Optimising Risk Assessment With CT-angiography or Calcium Score in Patients at High Risk for a Cardiovascular Event
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Coronary Artery Disease
Stroke
Peripheral Arterial Disease
Hypertension
Diabetes Mellitus, Type 2
Keywords: Cardiovascular diseases
Atherosclerosis
Multidetector Computed Tomography
Diabetes Mellitus, Type 2
Lead sponsor: UMC Utrecht
Sponsor class: OTHER
First posted: 2013-08-30
Enrollment: 1500
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study will be performed in consecutive patients entering the SMART study who are eligible according to the in- and exclusion criteria. SMART includes patients aged 18-79 years, who are newly referred to the University Hospital Utrecht with atherosclerotic cardiovascular disease insufficiency will be enrolled.

Brief summary: After having had a first cardiovascular event, there is a considerable risk of developing a subsequent event. Only recently, a risk prediction model was developed for this group of patients. Imaging techniques such as the coronary artery calcium score and contrast-enhanced computed tomography (CT) of the coronary and carotid arteries could be able to add improve this model. Imaging may further improve the prediction of future manifestations of arterial disease and personalize disease monitoring and treatment.

Detailed description: Patients with a prior cardiovascular event exhibit an elevated risk for subsequent cardiovascular events. The Second Manifestation of Arterial Disease Study (SMART) has recruited over 10,000 patients since 1996 with clinically manifest cardiovascular disease in a multidisciplinary single center study involving primary care physicians, cardiologists, neurologists, vascular surgeons, vascular medicine specialists and radiologists. Within this study a prediction model was developed to accurately estimate the risk for new cardiovascular events. It is now possible to acquire high-quality motion-free computed tomography (CT) images of the coronary and carotid arteries. Imaging biomarkers extracted from these images may further improve the prediction of future manifestations of arterial disease and personalize disease monitoring and medical care.

The SMART-ORACLE study is a prospective, single center, observational cohort study aiming to include 1500 patients. The primary aim is to identify predictors of future cardiovascular events. Eligible patients will be selected via the recruitment of the original SMART study. Patients participating in the SMART-ORACLE study will undergo calcium scoring in multiple cardiovascular beds and contrast-enhanced CT-scans of the coronary and carotid arteries in addition to the regular SMART investigations. Patients with renal dysfunction will be either excluded from the study or will receive pre-hydration (depending on eGFR) to minimize the risk of contrast nephropathy. Follow-up with questionnaire-based assessment will take place every 26 weeks until death of participant or end of the SMART study, asking participants about possible new cardiovascular events. Endpoints will be adjudicated by a committee of three experts. The aim is to collect 170 future events.

The main analysis will consist of Cox proportional hazard analysis. Imaging biomarkers will be added to the existing prediction model to assess their (independent) discriminatory capacity for future events. The c-statistic will be used to measure the discrimination of each model. Net reclassification improvement tables will be constructed to evaluate the added value of imaging markers in terms of reclassification. Based on a one-year-occurrence rate of subsequent cardiovascular events in the current SMART population database of 2.6%, about 6500 person years of follow-up are needed to obtain the adequate number of endpoints.

Eligibility criteria: Inclusion Criteria:

* History of cardiovascular event (coronary carter disease, cardiovascular disease, transient ischemic attack, minor stroke peripheral artery disease , abdominal aortic aneurysm)
* Diabetes Mellitus type 2
* Hypertension (Blood pressure\>140/90 mm Hg)

Exclusion Criteria:

* Known renal failure (defined as eGFR \<46 ml/min/1.73 m2 estimated based on the modification of diet in renal disease (MDRD) formula)
* Previous allergic reaction to contrast, necessitating medical intervention
* Other contra-indication for CT-scanning (e.g. pregnancy, acute hypotension (\<100 mm Hg systolic), clinical instability)
* Prior exposure to ionizing radiation for scientific purposes without advantage for the patient

Primary outcomes:
measure: Combined endpoint of cardiovascular events
timeFrame: Every 26 weeks until death of participant or end of the SMART study, with an expected average of 15 years
Secondary outcomes:
measure: Carotid artery intervention
timeFrame: Every 26 weeks until death of participant or end of the SMART study, with an expected average of 15 years
measure: Transient ischemic attack
timeFrame: Every 26 weeks until death of participant or end of the SMART study, with an expected average of 15 years
measure: Abdominal aorta aneurysm
timeFrame: Every 26 weeks until death of participant or end of the SMART study, with an expected average of 15 years
measure: Peripheral artery disease
timeFrame: Every 26 weeks until death of participant or end of the SMART study, with an expected average of 15 years
measure: Coronary artery intervention
timeFrame: Every 26 weeks until death of participant or end of the SMART study, with an expected average of 15 years
measure: All cause mortality
timeFrame: Every 26 weeks until death of participant or end of the SMART study, with an expected average of 15 years
Other outcomes:
Locations:
city: Utrecht
country: Netherlands
facility: UMC Utrecht
Study officials:
affiliation: UMC Utrecht
name: Yolanda van der Graaf, Prof. dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Simons PC, Algra A, van de Laak MF, Grobbee DE, van der Graaf Y. Second manifestations of ARTerial disease (SMART) study: rationale and design. Eur J Epidemiol. 1999 Oct;15(9):773-81. doi: 10.1023/a:1007621514757.
citation: Dorresteijn JA, Visseren FL, Wassink AM, Gondrie MJ, Steyerberg EW, Ridker PM, Cook NR, van der Graaf Y; SMART Study Group. Development and validation of a prediction rule for recurrent vascular events based on a cohort study of patients with arterial disease: the SMART risk score. Heart. 2013 Jun;99(12):866-72. doi: 10.1136/heartjnl-2013-303640. Epub 2013 Apr 10.