The SMART-ORACLE Study

Stroke Clinical Trial

— SMART-ORACLE  

Official title:

Optimising Risk Assessment With CT-angiography or Calcium Score in Patients at High Risk for a Cardiovascular Event

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT01932671
• Other study ID #: NL36828.041.11
• Status: Enrolling by invitation
• Phase: N/A
• First received: August 18, 2013
• Last updated: August 27, 2013
• Start date: August 2012

Study information

• Verified date: August 2013
• Source: UMC Utrecht
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: Medical Ethics Review Committee (METC)
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 1500
• Est. primary completion date: September 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Hypertension
• Myocardial Ischemia
• Peripheral Arterial Disease
• Peripheral Vascular Diseases
• Stroke

Locations

Country	Name	City	State
Netherlands	UMC Utrecht	Utrecht

Sponsors (1)

Lead Sponsor	Collaborator
UMC Utrecht

Country where clinical trial is conducted

Netherlands, 

References & Publications (2)

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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Combined endpoint of cardiovascular events	(non-fatal) ischemic stroke (non-fatal) myocardial infarction (cardio)vascular death Endpoints will be adjudicated by a committee of three experts.	Every 26 weeks until death of participant or end of the SMART study, with an expected average of 15 years	No
Secondary	Carotid artery intervention	Carotid desobstruction or stenting	Every 26 weeks until death of participant or end of the SMART study, with an expected average of 15 years	No
Secondary	Transient ischemic attack		Every 26 weeks until death of participant or end of the SMART study, with an expected average of 15 years	No
Secondary	Abdominal aorta aneurysm	Non-fatal rupture, stenting or operation of an abdominal aorta aneurysm	Every 26 weeks until death of participant or end of the SMART study, with an expected average of 15 years	No
Secondary	Peripheral artery disease	Amputation, percutaneous transluminal angioplasty or stenting due to peripheral artery disease	Every 26 weeks until death of participant or end of the SMART study, with an expected average of 15 years	No
Secondary	Coronary artery intervention	Percutaneous coronary intervention, coronary artery bypass graft	Every 26 weeks until death of participant or end of the SMART study, with an expected average of 15 years	No
Secondary	All cause mortality		Every 26 weeks until death of participant or end of the SMART study, with an expected average of 15 years	No

External Links

•   Information about SMART study