Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

Visualization of Asymptomatic Atherosclerotic Disease for Optimum Cardiovascular Prevention (VIPVIZA)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Västerbotten County Council, Sweden
Information provided by (Responsible Party):
Umeå University
ClinicalTrials.gov Identifier:
NCT01849575
First received: May 3, 2013
Last updated: October 28, 2016
Last verified: December 2015

May 3, 2013
October 28, 2016
April 2013
June 2021   (final data collection date for primary outcome measure)
Framingham score evaluation [ Time Frame: 12 and 36 months ] [ Designated as safety issue: No ]
Composite gender-specific algorithm used to estimate the 10-year cardiovascular risk of an individual, based on levels of blood pressure, total cholesterol, LDL-cholesterol, systolic bloodpressure, treatment for high blood pressure, diabetes, smoking and age
Conventional cardiovascular risk factors [ Time Frame: 12 month ] [ Designated as safety issue: No ]
S-LDL-cholesterol, S-triglycerides, S-cholesterol, Systolic and diastolic Blood pressure, HbA1c, fasting glucose, BMI, waist, SCORE evaluation
Complete list of historical versions of study NCT01849575 on ClinicalTrials.gov Archive Site
  • SCORE evaluation [ Time Frame: 12 and 36 months ] [ Designated as safety issue: No ]
    Risk of death in myocardial infarction within 10 years expressed as statistical assessment based on smoking, systolic blood-pressure, blood cholesterol, age and sex.
  • Life style [ Time Frame: 12 and 36 months ] [ Designated as safety issue: No ]
    Patient questionnaire. Composite measure.
  • Hospitalizations due to stroke and myocardial infarctions [ Time Frame: 5 and 10 years ] [ Designated as safety issue: No ]
    Data will be collected from computerized medical records from hospital care in the county and from the In-patient registry at the National Board of Health and Welfare.
  • Hospitalizations due to revascularizations [ Time Frame: 5 and 10 years ] [ Designated as safety issue: No ]
    Data will be collected from the Causes of Deaths registry at the National Board of Health and Welfare.
  • Cause-specific mortality due to myocardial infarctions and stroke [ Time Frame: 5 and 10 years ] [ Designated as safety issue: No ]
    Data will be collected the Causes of Deaths registry at the National Board of Health and Welfare.
  • Total mortality [ Time Frame: 5 and 10 years ] [ Designated as safety issue: No ]
    Data will be collected from computerized medical records from hospital care in the county, regional quality registry on myocardial infarctions and from the In-patient registry at the National Board of Health and Welfare.
  • Carotid ultrasonography results [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    Compound measure
Life style [ Time Frame: 12 month and three years ] [ Designated as safety issue: No ]
Patient questionnaire
Pharmacological treatment, composite outcome [ Time Frame: 1, 3 and 5 years after baseline ] [ Designated as safety issue: No ]

Prescriptions of medications for hypertension, diabetes and dyslipidemia. Data collected from computerized medical records in primary and hospital care in the county.

Purchases of medications for hypertension, diabetes and dyslipidemia followed through data from the Pharmaceutical registry, National Board of Health and Wellfare

  • Ultrasound results [ Time Frame: Three years from baseline ] [ Designated as safety issue: No ]
    Carotid Intima Media Thickness Carotid plaques: Total plaque area, Grey scale median (GSM)
  • Pharmacological treatment [ Time Frame: 1, 3 and 5 years after baseline ] [ Designated as safety issue: No ]

    Prescriptions of medications for hypertension, diabetes and dyslipidemia. Data collected from computerized medical records in primary and hospital care in the county.

    Purchases of medications for hypertension, diabetes and dyslipidemi followed through data from the Pharmaceutical registry, National Board of Health and Wellfare

  • Hard endpoints [ Time Frame: Within five years ] [ Designated as safety issue: No ]
    Hospitalizations due to myocardial infarctions (MI), stroke, PCI and other revascularizating surgical procedures, and deaths (all-cause and CVD specific). Data will be collected from computerized medical records from primary and hospital care in the county, regional quality registers on MI and stroke and from the In-patient and Causes of Deaths registers, at the National Board of Health and Welfare.
 
Visualization of Asymptomatic Atherosclerotic Disease for Optimum Cardiovascular Prevention
Direct VIsualiZAtion of Asymptomatic Atherosclerotic Disease for Optimum Cardiovascular Prevention. A Population Based Pragmatic Randomised Controlled Trial Within Västerbotten Intervention Programme (VIP) and Ordinary Care.

This population based randomized controlled trial (RCT) aims at optimizing cardiovascular disease (CVD) prevention through accurate identification of individuals at high risk of CVD and accurate perception of the risk, and better compliance to preventive treatments and reduced premature CV morbidity and mortality Increased carotid artery intima-media thickness (CIMT) and carotid plaques, assessed by ultrasonography, are early signs of atherosclerosis and associated with myocardial infarction and stroke. Few studies have systematically evaluated image-based risk stratification and its effect on clinical outcomes and results are conflicting.

The Västerbotten Intervention Programme (VIP), Northern Sweden, is integrated in primary care services with assessment of traditional CV risk factors and individual health promoting counseling for all 40-, 50- and 60-year olds (n=6500/yr). Those with diabetes, hypertension, family history of premature CVD and/or hypercholesterolemia are referred to treatment.

VIP participants with at least one conventional CV risk factor (60% of participants) are eligible for inclusion in VIPVIZA. During 2013-2015, 3200 participants will be enrolled. Portable carotid ultrasound machines will be used for ultrasound examinations, whereby CIMT and plaque formation will be visualized and measured.

Subjects will be randomly assigned to one of two groups; 1/ Intervention: Written information to patient and physician, including graphic presentation in color of CIMT and of plaque, vascular age, an ultrasound image, general information about atherosclerosis as a dynamic process, and recommendation to follow clinical guidelines for risk factor control. 2/ Control: No information from the baseline ultrasonography.

We will explore determinants of behavioral change using psychometric questionnaires and level of health literacy. Deep interviews at the time point for the ultrasound examinations will explore how the screening relates to risk perception, quality of life, coping strategies, attitudes to and skills of self-care.

Both groups will be managed according to clinical guidelines within the usual health care. After three years (2015-2017), the ultrasonography is repeated and information given to all participants and their physicians.

CV risk factors, life style and pharmacological treatments will be assessed after one and three years. CV morbidity and mortality and all-cause mortality will be followed during five years, i.e. until 2020.

Visualization of asymptomatic atherosclerotic disease to improve cardiovascular prevention. Design of a randomized controlled intervention within ordinary health care - VIPVIZA.

Design and methods: a randomized controlled trial integrated in the existing set-up for population based CVD screening and prevention within primary health care, the Västerbotten Intervention Programme (VIP). VIP provides CVD risk factor screening and individual health promotion to all county citizens at ages 40, 50 and 60 years with high participation rate (around 70%), only small social selection bias and standardized procedures.

Study population: VIP-participants were invited to the study according to inclusion criteria. This design guarantees a population base for the study, focus on individuals at intermediate CVD-risk, clinical relevance and external validity.

Sample size and power: Power calculations were based on VIP data on CVD risk factors 2011, and on CIMT data from the Tromsö study, Norway. Enrolment of 3200 participants was estimated sufficient to test outcomes with a probability of 0.8 to detect a true difference between groups at a significance level of 0.05. To compensate for drop-outs during the study period, of 3600 individuals were recruited.

Population sample Inclusion criteria: i) age 60 years, ii) a history of CVD before age 60 years among first-degree relatives iii) age 50 years and at least one of the following: smoking, diabetes, hypertension, S-LDL-cholesterol ≥ 4.5 mmol/L, abdominal obesity.

Exclusion criteria: a significant stenosis as defined by >50% luminal narrowing of the investigated carotid arteries according to vascular ultrasound and Doppler measurements.

Participants are randomly with equal probability assigned to two groups. Intervention Image-based risk communication, i.e. visual information about carotid ultrasound results, to the participant and his/her primary care physician in the form of atherosclerosis highlighted graphically in color against normal vascular age patterns and as plaque formation. After 2─4 weeks a follow─up call by a research nurse, to give additional information and reassurance, if needed.

Control No information about the carotid ultrasound to participant and physician.

Both groups are followed and managed according to clinical guidelines within primary health care during the entire study period.

Outcome definitions for differences between intervention and control group:

Primary outcome: CVD risk as evaluated by statistical risk model based on conventional risk factors at one year. Variable: Framingham risk score at one-year follow-up (Specific aim 1). This is a surrogate variable for change of atherosclerosis as assessed by carotid intima media thickness and presence of plaque. The atherosclerotic process is too slow and the precision in ultrasound measurements too low to allow for evaluations between intervention and control group after one year.

Secondary outcomes: The secondary outcomes are divided into three categories, corresponding specific aims are indicated.

  1. CVD risk factors, measured with standard clinical methods (variables: blood pressure, Lipids, glucose values, BMI) and lifestyle, (Physical activity, tobacco use, alcohol (AUDIT), diet) measured with questionnaires at baseline, 1-year and 3-year visits. (Specific aims 1).
  2. Atherosclerotic disease, i.e. Ultrasound results at baseline and year 3: carotid intima media thickness (CIMT), presence of plaque and presence and degree of stenosis. A portable automatic carotid ultrasound equipment (CardioHealth Station®, Panasonic Healthcare Co., Ltd, Tokyo, Japan) is used. A standardized protocol according to current guidelines is applied and the angle of insonation is automatically provided by the system and recorded. Measurement of CIMT (max, min and mean values) is automatic (Specific aims 1).
  3. Pharmacological treatment will be followed through the Pharmacological register and medical records (Specific aims 2, 4)
  4. Novel biomarkers: Plasma samples collected at baseline and at the 3-year follow-up will be longitudinally analyzed for novel hypothesized CVD biomarkers. For Lipidomics collaboration is established with Umeå Plant Science Centre, for Protein biomarkers SciLifeLab in Uppsala (Specific aim 3).
  5. Clinical endpoints will be followed through registers on hospitalizations and causes of deaths (all-cause and CVD specific): Myocardial infarctions (MI), stroke, revascularization procedures (Specific aim 5).

Psychological and behavioral factors, determinants and mediators of preventive actions:

  1. Validated psychometric questionnaires at baseline and 3.year follow-up: e.g. Health related quality of life (Rand 36), Self efficacy (The General Self-efficacy test), coping strategies (Brief COPE), Optimism (Life Orientation Test-Revised), social network and support (ISSI), work stress (Karasek demand/control model) (Specific aim 2)
  2. Social support and network, education, civil status, stress at work, quality of life: VIP-data.
  3. Barriers and facilitators for primary CVD prevention explored through deep interviews with physicians and participants and evaluated with qualitative methods (Specific aim 4)

Data analyses, statistical analytical tests: Parametric and non-parametric tests will be used as appropriate. Imaging results will be related to the risk factors establishing multiple linear regression models. Predictive Cox Proportional Hazard models will be developed to estimate the overall predictive ability of CIMT, plaque and risk factors on CVD morbidity and mortality at 5 and 10 years taking into account time at risk for disease and deaths. Receiver Operating Characteristic Curves (ROC) by estimating the Area Under the Curve (AUC) to assure highest possible sensitivity and specificity of predictions. Confirmatory (structural equation modelling) and exploratory (partial least squares analysis) statistical modelling employed to establish relationships between the intervention and intermediate and mediating factors and variables' relative contribution to explain changes in the outcome variables.

Qualitative analyses, Deep interviews with participants and physicians will be transcribed verbatim and analyzed using Qualitative Content Analysis.

Time plan: Recruitment and base line measurements were completed June 2016 (In VIP: CVD risk factors, life style questionnaire and sampling of frozen blood to the Medical Biobank. Carotid ultrasound and psychometric questionnaires, interviews).

1-year follow-up started May 2014, will be completed June 2017. (CVD risk factors, life style questionnaire) 3-year follow-up starts August 2016, will be completed June 2019 (CVD risk factors, life style questionnaire, frozen blood samples, carotid ultrasound and psychometric questionnaires, pharmacologic treatments.

5 and 10-year follow-up for clinical events, register data 2021 and 2026. Period for this application: 2017-2019, the second phase of data collection from participants.

Implementation: The project is conducted as an integrated part of clinical care. Evaluations and prevention based on ultrasound results and risk factors are done by family physicians according to clinical guidelines in routine care. The carotid ultrasound examinations are performed with a portable machine that can easily be used in settings outside specialized care. The procedure takes only 10-15 minutes, the methodology is user friendly and automated, follows a strict protocol, and can after a short learning period be performed by non-specialized staff. The existing software provides a report that can accurately be interpreted by patients and doctors. Therefore, the results and methods are expected to be relevant, valid and ready for direct implementation in other CVD prevention programs, including being decentralized and performed on an everyday basis in high volumes by non-specialized staff. If necessary, evaluations by a specialist can be done at long distances within specialized care as ultrasound results can be electronically transferred.

Organisation: The source population is the whole middle-aged county population, from the more densely-populated urbanized coastland to the sparsely-populated rural inland. The research environment is interdisciplinary with a strong multi-professional team of researchers with solid experience of clinical prevention and research in the field. For the practical project work a close collaboration is important between the applicant and the medical coordinator of VIP with representatives of Heart Centre including Clinical Physiology, Stroke center, Behavioral Medicine. Additional specialists in the team are; cardiology, image based techniques, internal medicine, family medicine, behavioral medicine, epidemiology and global health, psychology, statistics, qualitative methods. For biomarker research we collaborate with, Umeå Plant Science Centre (omics), SciLifeLab Uppsala, and Uppsala Clinical Research Center. Research on ultrasound technical development is a collaboration between Heart Centre and Departments of Biomedical Engineering and Radiation Sciences. Agreements about premises, staff, research nurses and technicians are made long-term. The County Council has authorized the study all over the county.

Premises and facilities: The daily work is managed and organized by experienced research nurses at the Clinical Research Centre, Umeå University Hospital, where about 50% of the ultrasound examinations are performed. In the remote districts they are performed at the primary health care centers with use of the same portable ultrasound machine. VIP-nurses working continuously with prevention at each PHC are deeply involved for recruitment and 1- and 3-year follow-up measurements. The Clinical Trial Unit, another research supporting facility hosted by the county council, will monitor the trial according to GCP.

ETHICAL APPROVAL All individuals participating in the study has to provide written informed consent. The Regional Ethical Review Board, Umeå University, has approved the VIPVIZA study including the above described substudies (Dnr 2011-445-31M,2012-463-32M, 2013-373-32M) .

Interventional
Not Provided
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Cardiovascular Diseases
Behavioral: Intervention

Information about carotid ultrasound results to the participant and his/her primary care physician in the form of atherosclerosis highlighted graphically in color against normal vascular age patterns and as plaque formation. General information about atherosclerosis as a dynamic modifiable process and recommendation to follow clinical guidelines for risk factor control. After 2─4 weeks a follow─up call by a research nurse, to give additional information and reassurance, if needed. Identical information to the study participant is sent by post after 6 months.

CVD risk factors are managed according to clinical guidelines within primary health care during the entire study period.

Other Name: Information about ultrasound results
  • Active Comparator: Intervention
    The intervention: Giving communication about risk of cardiovascular disease in the form of written and graphical information about silent atheroscslerosis measured by carotid ultrasound examination as carotid intima-media thickness, highlighted as vascular age, and plaque formation, visualized as a traffic light (green - no plaque, red - plaque).The ultrasound results are given to the study person and his/her physician, in addition to information about conventional risk factors for cardiovascular disease
    Intervention: Behavioral: Intervention
  • No Intervention: Control
    The comaparator is that the study person and his/her physician do not get any information about carotid ultrasound results on silent atherosclerosis. They are only informed about results of measured conventional CVD risk factors

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
3813
June 2021
June 2021   (final data collection date for primary outcome measure)

Inclusion Criteria:

- Participant in the Västerbotten Intervention Programme

and

  • 40 years old and a history of CVD at age < 60 years among first-degree relative

or

  • 50 years old and at least one of the following six criteria:
  • a history of CVD at age < 60 years among first-degree relative,
  • smoking,
  • diabetes,
  • hypertension,
  • S-LDL-cholesterol ≥4.5 mmol/L,
  • abdominal obesity

or

  • 60 years old

Exclusion Criteria:

  • Stenosis ≥50% of the carotid lumen
Both
40 Years to 60 Years   (Adult)
Yes
Contact information is only displayed when the study is recruiting subjects
Sweden
 
NCT01849575
VIPVIZA version 20121204
No
No
Not Provided
Umeå University
Umeå University
Västerbotten County Council, Sweden
Principal Investigator: Margareta Norberg, MD, PhD Umeå University
Principal Investigator: Ulf Näslund, Professor,MD Umeå University Hospital
Umeå University
December 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP