Clinical trial NCT01849575: Visualization of Asymptomatic Atherosclerotic Disease for Optimum Cardiovascular Prevention
Official title: 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.
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Cardiovascular Diseases
Keywords: Ultrasonography
Cardiovascular diseases
Prevention
Risk communication
Risk assessment
Behavioral change
Lead sponsor: Umeå University
Sponsor class: OTHER
Collaborators: name: Västerbotten County Council, Sweden
First posted: 2013-05-08
Enrollment: 3532
Sex: ALL
Minimum age (years): 40
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of VIPVIZA is to assess the impact of pictorial information about asymptomatic atherosclerotic disease to both physician and patient, for improving physicians' adherence to prevention guidelines and patient perception and understanding of the cardiovascular disease (CVD) risk and consequent motivation for prevention. The intervention effect is assessed by differences between randomization groups in the primaryboutcome Framingham Risk Score (FRS) and the secondary outcomes the Systematic COronary Risk Evaluation (SCORE) as well as changes in these scores after one, three and six years. Secondary outcomes are also atherosclerotic disease progression, as assessed by repeated carotid ultrasound examination after three and six years, as well as the prevalence of acute events and mortality after 10 years . Social, psychological and cognitive determinants of behavioral change as well as the intervention impact on novel biomarkers will also be explored.

Detailed description: Project description

The main objective of this project is to contribute to improved primary prevention of cardiovascular disease through the provision of a visual image and pictorial report of atherosclerosis while still asymptomatic. The image and report are seen and discussed by both physician and patient in order to improve guideline adherence and patient perception and understanding of the CVD risk and consequent motivation for prevention. The specific objectives include: 1. To assess the prevalence of asymptomatic atherosclerotic disease in men and women through identification of carotid plaques and measurement of carotid intima-media thickness (CIMT), and to relate plaques and CIMT to clinically estimated CVD risk factors and risk scores; 2. To explore the impact of pictorial representations of atherosclerosis on physicians´ adherence to prevention guidelines, and on individuals' quality of life, preventive measures, risk factor control and progress of atherosclerotic disease over the course of three and six years, as well as on premature CVD morbidity and mortality over the course of 5 and 10 years; 3. To evaluate how individuals' social, psychological, and cognitive characteristics relate to health behaviours, atherosclerosis and CVD risk at baseline and progression of any atherosclerosis; 4. To investigate biomarkers in relation to CIMT and plaques at baseline, changes in conventional CVD risk markers and lifestyle, and progression of atherosclerosis.

Survey of the field Primary prevention of CVD often fails due to poor adherence among practitioners and patients to evidence-based prevention guidelines on effective modification of risk factors by lifestyle change and pharmacological treatment. Contributory factors include poor communication about the CVD risk by the physician and inaccurate risk perception among patients. The risk message is usually communicated verbally or numerically, while potentially more effective visual tools are seldom used. For the clinical assessment of CVD risk the FRS and the European SCORE are most widely used. However, evidence that their use translates into reduced CVD morbidity and mortality is scarce. These risk scores focus on high-risk individuals, despite 60-70% of all CVD events occurring among individuals at low or intermediate risk for CVD. They might also be too abstract to lead to accurate risk perception and to motivate individuals to take preventive actions; information alone seldom results in rational behavior modification. VIPVIZA takes a different approach from current practice for the prevention of CVD. Instead of being based solely on indirect risk factors, this project evaluates the atherosclerotic disease itself while it still is subclinical, providing improved assessment, communication and perception of the CVD risk and hence greater motivation for prevention. This is achieved with ultrasonography of medium sized arteries with assessment of CIMT and existing atherosclerotic plaques.

Design, setting and study population:

The study is a pragmatic randomised open-label controlled trial with blinded evaluators (PROBE). VIPVIZA is integrated in and added to the ordinary Västerbotten Intervention Programme (VIP). Individuals with at least one clinical CVD risk factor were invited to the VIPVIZA trial when they participated in VIP (n=4177), resulting in inclusion of 3532 participants. Baseline visits with ultrasound examinations were carried out from April 29 2013 to June 7 2016. Participants were consecutively and randomly allocated to two groups (intervention and control group) using a computer-generated randomization list. The ultrasound examinations in VIPVIZA at baseline as well as after three and six years are performed at the hospitals in the three cities/towns (Umeå, Skellefteå, Lycksele), and in remote rural areas at primary health care centres. Risk factor measurements and questionnaires at follow-up after one, three and six years are carried out for participants living in Umeå at the Clinical Research Centre at Umeå University Hospital, and for participants in the rest of the county at their local primary health care center. Both groups are managed according to clinical guidelines for CVD prevention within primary care (not by the study team).

Intervention At baseline, pictorial representation of the carotid ultrasound results was given to each participant in the intervention group and their primary care physician. Atherosclerosis was presented as vascular age, with a gauge ranging from green through yellow, orange and red to illustrate the individual's biological age compared to chronological,age. A red or a green circle, like a traffic light, illustrated detected or no detected plaque, respectively. Brief written information about atherosclerosis as a dynamic process that is modifiable by a healthy lifestyle and pharmacological treatment, an interpretation of the result and general advice on CVD prevention were included. After 2-4 weeks, participants received a follow-up phone call by a research nurse in order to reassure and give additional information as needed. The same pictorial information was repeated to participants after 6 months. No information about the ultrasound result was given to the control group and their physicians.

At three- and six-year follow-up both the intervention and the control group participants and their respective primary care physician receive information about ultrasound results with the same format as was given to the intervention group at baseline. Thus, the intervention is completed at the time-point for three-year follow-up. After that the two groups are continuously followed through registries and compared with respect to atherosclerosis development and hard outcomes.

Data collection:

Clinical risk factors for cardiovascular disease: Measured at the baseline VIP health survey, at 1-, 3- and 6-year follow-up (blood pressure, lipids, and glucose, BMI and waist circumference).

Questionnaires: The VIP questionnaire covers health, socioeconomic situation, quality of life (RAND 36), lifestyle (physical activity, tobacco and alcohol consumption, diet), working conditions, social network. Validated psychometric instruments at baseline and 3-year follow-up included health literacy, coping strategies, an optimism-pessimism scale, self-efficacy, HADS and self-rated risk of CVD. Perceptions about preventive medication and a stress questionnaire at the 3-year follow-up. At 3-year follow-up questions on health literacy, coping strategies and optimism/pessimism are replaced by questionnaires on personality and dental care.

Carotid ultrasound examinations are performed at baseline, after 3 and6 years according to a standardized protocol.

Interviews: With subsamples of participants after the first, second and third ultrasound examination, and with primary care physicians after the first ultrasound examination.

Stored samples of blood to the Medical Biobank: This is done at the baseline VIP visit and at 3- and 6-year follow-up among participants, to be used for analyses of novel biomarkers Register data: Prescriptions, visits and risk factor measurements from the medical records system in Västerbotten County. Dental health and dental radiological examinations from Dental care. The Prescriptions register, Hospitalizations register and Causes of deaths register at the National Board of Health and Welfare. In addition, physical and psychological functioning and blood-group at military patterning at age around 18 from the Conscripts registry (for male participants only), educational level and income from Statistics Sweden and air pollutants by geographical region in the County of Västerbotten.

Time plan The study progress is largely according to the plan. Baseline examinations were conducted April 2013-June 2016, the 1-year follow-up examinations June 2014-August 2017, and the 3-year examinations September 2016 - June 2019. The six-year follow-up examinations started December 2019 which is a delay of 6 months due to administrative reasons. Register data from medical records, Statistics Sweden, the Conscripts register, Air-borne pollutants are underway April 2020. Data on morbidity and mortality will be retrieved in 2027, i.e. one year later than 10 years after trial start due to delay until data on events has been entered into the registries.

Ethical approval:

Study protocol version 4.0:

The VIPIVZA trial: Dnr 2011-445-32M date Feb 7 2012. Amendment 1: Dnr 2012-463-32M date December 19 2012. Amendment 2: Dnr 2013 373-32M date October 15 1013. Amendment 3: Dnr 2016-245-32M date May 31 2016. Amendment 4: Dnr 2017-95-32M date February 27 2017. Amendment 5: Dnr 2018-182-32 date May 28 2018.

Study protocol version 5.0:

Amendment 6: Dnr 2018-482-32M Date December 27 2018. Amendment 7: Dnr 2019-04619 Date September 24 2019.

Eligibility criteria: 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

Primary outcomes:
measure: FRS
timeFrame: one year
Secondary outcomes:
measure: SCORE
timeFrame: Follow-up after one year
measure: Hospitalizations Due to Stroke, Myocardial Infarctions and Re-vascularizations
timeFrame: 10 years
measure: Total Mortality and Cause-specific Mortality Due to Myocardial Infarctions and Stroke
timeFrame: 10 years
measure: Total Mortality
timeFrame: 10 years
measure: Carotid Atherosclerosis
timeFrame: 3 years after baseline
Other outcomes:
measure: FRS, Adjusted for Baseline Values
timeFrame: Follow-up after three years during September 5 2016 - May 28 2019
measure: SCORE Adjusted for Baseline Levels
timeFrame: Three years of follow-up, data collected during September 5 2016 - May 28 2019
Locations:
city: Umeå
country: Sweden
facility: Clinical Reseach Center Umeå University Hospital
Study officials:
affiliation: Umeå University
name: Patrik Wennberg, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Umeå University Hospital
name: Ulf Näslund, Professor,MD
role: PRINCIPAL_INVESTIGATOR
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