The SMART-ORACLE Study

This study is enrolling participants by invitation only.
Sponsor:
Information provided by (Responsible Party):
Prof. dr. Y. van der Graaf, UMC Utrecht
ClinicalTrials.gov Identifier:
NCT01932671
First received: August 18, 2013
Last updated: August 27, 2013
Last verified: August 2013
  Purpose

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.


Condition
Coronary Artery Disease
Stroke
Peripheral Arterial Disease
Hypertension
Diabetes Mellitus, Type 2

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Optimising Risk Assessment With CT-angiography or Calcium Score in Patients at High Risk for a Cardiovascular Event

Resource links provided by NLM:


Further study details as provided by UMC Utrecht:

Primary Outcome Measures:
  • Combined endpoint of cardiovascular events [ Time Frame: Every 26 weeks until death of participant or end of the SMART study, with an expected average of 15 years ] [ Designated as safety issue: No ]
    (non-fatal) ischemic stroke (non-fatal) myocardial infarction (cardio)vascular death Endpoints will be adjudicated by a committee of three experts.


Secondary Outcome Measures:
  • Carotid artery intervention [ Time Frame: Every 26 weeks until death of participant or end of the SMART study, with an expected average of 15 years ] [ Designated as safety issue: No ]
    Carotid desobstruction or stenting

  • Transient ischemic attack [ Time Frame: Every 26 weeks until death of participant or end of the SMART study, with an expected average of 15 years ] [ Designated as safety issue: No ]
  • Abdominal aorta aneurysm [ Time Frame: Every 26 weeks until death of participant or end of the SMART study, with an expected average of 15 years ] [ Designated as safety issue: No ]
    Non-fatal rupture, stenting or operation of an abdominal aorta aneurysm

  • Peripheral artery disease [ Time Frame: Every 26 weeks until death of participant or end of the SMART study, with an expected average of 15 years ] [ Designated as safety issue: No ]
    Amputation, percutaneous transluminal angioplasty or stenting due to peripheral artery disease

  • Coronary artery intervention [ Time Frame: Every 26 weeks until death of participant or end of the SMART study, with an expected average of 15 years ] [ Designated as safety issue: No ]
    Percutaneous coronary intervention, coronary artery bypass graft

  • All cause mortality [ Time Frame: Every 26 weeks until death of participant or end of the SMART study, with an expected average of 15 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 1500
Study Start Date: August 2012
Estimated Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)
Groups/Cohorts
SMART
The SMART (Second Manifestation of ARTerial disease) cohort comprises patients at high-risk for or who have clinically manifest cardiovascular disease, including transient ischemic attack, cerebrovascular disease, peripheral artery disease, aneurysma aorta abdominalis, myocardial infarction, coronary ischemia for which coronary intervention is required, renal artery stenosis, diabetes mellitus, hyperlipidemia, hypertension, patients diagnosed with human immunodeficiency virus, pre-eclampsia, HELLP syndrome, abruption placentae and Intrauterine growth restriction in medical history. Participants are re-invited after 4 years for a second screening. This screening is performed to study the progression of atherosclerosis and evaluate the effects of the advice of the multidisciplinary team.

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01932671

Locations
Netherlands
UMC Utrecht
Utrecht, Netherlands, 3508 GA
Sponsors and Collaborators
UMC Utrecht
Investigators
Principal Investigator: Yolanda van der Graaf, Prof. dr. UMC Utrecht
  More Information

Additional Information:
Publications:
Responsible Party: Prof. dr. Y. van der Graaf, UMC Utrecht
ClinicalTrials.gov Identifier: NCT01932671     History of Changes
Other Study ID Numbers: NL36828.041.11
Study First Received: August 18, 2013
Last Updated: August 27, 2013
Health Authority: Netherlands: Medical Ethics Review Committee (METC)

Keywords provided by UMC Utrecht:
Cardiovascular diseases
Atherosclerosis
Multidetector Computed Tomography
Diabetes Mellitus, Type 2

Additional relevant MeSH terms:
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Diabetes Mellitus
Diabetes Mellitus, Type 2
Hypertension
Stroke
Peripheral Arterial Disease
Peripheral Vascular Diseases
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Atherosclerosis

ClinicalTrials.gov processed this record on April 16, 2014