Akershus Cardiac Examination (ACE) 5 Study: Pragmatic Randomized Controlled Trial of Lung Cancer Screening Plus Program to Improve Cardiovascular Risk Profile and Health in Individuals With Heavy Smoking History
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 1,000
- 试验地点
- 2
- 主要终点
- Number of people reaching treatment goals or started new GDMT for smoking, lipid concentrations, blood pressure, and HbA1c
研究概览
简要总结
Individuals with extensive smoking history have 2- to 3-fold increased risk of dying prematurely compared to age- and gender-matched peers. Historical data indicate that 55% of heavy smokers will die from cardiovascular disease (CVD), while approximately 5% will die from lung cancer. Lung cancer screening programs are currently being implemented worldwide, but efforts to reduce also CVD are not included.
The research group behind the ACE 5 Study are affiliated with the study team behind the implementation study of lung cancer screening in Norway ("Tidlig oppdagelse av lungekreft [TIDL]"). The TIDL Study have performed non-contrast, non-cardiac chest CT-based screening for lung cancer in 1000 individuals. Prior studies have demonstrated that a visual four-group classification of coronary artery calcification using non-contrast, non-cardiac chest CT images provide an easily available, non-invasive surrogate index for subclinical and established chronic coronary syndrome. Accordingly, the 2024 European Society of Cardiology guidelines for chronic coronary syndrome promotes that opportunistic screening for atherosclerotic CVD (ASCVD) should be performed when non-contrast, non-cardiac chest CT images are available ("IIa recommendation"). The investigators will now invite TIDL participants for a second study, the Akershus Cardiac Examination (ACE) 5 Study, which will assess whether intervention also against ASCVD ("Lung Cancer Screening Plus Program") will improve cardiovascular risk profile and cardiovascular health in individuals with heavy smoking history.
The ACE 5 Study will be a separate study with separate protocol and consent as the ACE 5 Study will focus on the prevention of CVD in individuals with heavy smoking history as add-on to lung cancer screening. The ACE 5 Study will assess the combined effect of (1) non-contrast, non-cardiac chest CT images as basis for ASCVD detection, and (2) the value of a hospital-based, nurse-led follow-up program to improve cardiovascular risk profile and cardiovascular health in individuals with heavy smoking history. Whether a Lung Cancer Screening Plus Program can improve cardiovascular risk profile and indices of improved cardiovascular health compared to the current strategy/standard in individuals with heavy smoking history is currently not known. The primary endpoint relates to status for cardiovascular risk profile after 1-year follow-up, and the study will use pre-defined cutoffs for the different risk factors based on relevant European Society of Cardiology (ESC) Guidelines, especially the 2021 ESC guidelines for primary prevention and the 2024 ESC guidelines for chronic coronary syndrome.
详细描述
Background - The pathophysiology of chronic coronary syndrome
Myocardial infarction is the number 1 cause of death among smokers. An underlying framework related to this project is the potential to detect and treat atherosclerotic cardiovascular disease (ASCVD), which primarily manifests as coronary artery disease (CAD), prior to the development of symptoms and clinical events. This is important as CAD could be an unstable condition where acute occlusion of coronary arteries will lead to immediate myocardial necrosis, which is referred to as acute myocardial infarction. Smoking is a principal risk factor for atherosclerotic plaques and later symptomatic CAD. Myocardial infarction has significant mortality, both in the acute phase and later due to post-infarction heart failure mortality as well as recurrent myocardial infarction. As many as 1/5 of all patients having a myocardial infarction experience sudden cardiac death as their first symptom. Strategies that can detect CAD prior to events that leads to symptoms (subclinical disease) is therefore highly desirable.
Background - Lung Cancer Screening Programs and risk stratification for CVD
Lung cancer screening programs represent an excellent opportunity to screen high-risk individuals for ASCVD. Non-contrast, non-cardiac chest CT is the cornerstone of lung cancer screening and performed in all lung cancer screening participants. With these CT scans, the investigators can assess coronary artery calcification (CAC) with acceptable accuracy, either by using the four-group visual score or other method, like calculating Agatston score or ordinal visual scores. Moreover, as contrast agents are not required for the cardiac assessment and there is no need for ECG-triggering or cardiac specific protocols, the CT scans will not represent any risk to participant health or put additional strain on health services performing lung cancer screening. Radiation from current CT scans for lung cancer screening is 1.5-3 mSv, which is below the background radiation.
The clinical value of CACS by both Agatston, ordinal visual scores and the four-group visual score has been demonstrated in several studies, and the investigators believe that specific characteristics of our screening population will make assessing coronary artery calcification especially valuable for identifying subclinical CAD in the ACE 5 Study population. Assessment of CAC is also recommended by the National Lipid Association and the 2016 SCCT/STR guidelines for coronary artery calcium scoring of non-contrast noncardiac chest CT scans. One caveat of using coronary artery calcification to screen for subclinical CAD in the general population has been a very small number of individuals with CACS=0 that still experience cardiovascular events during follow-up. While CAC=0 is considered the one most important negative risk factor, a study of CAC in the lung cancer screening setting with non-contrast noncardiac chest CT scans show that up to 10% of the scans with CAC=0 experienced a major cardiac event. Hence, it is suggested that when CAC is assessed in noncardiac chest CT scans, CAC=0 should not always lead to delayed or avoidance of pharmacotherapies.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Screening
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 60 Years 至 79 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •used for the lung cancer screening implementation study/ TIDL Study:
- •Women and men
- •Ages 60 to 79 years old (inclusive)
- •A smoking history of at least 35 pack-years and 1) being a current smoker or a former smoker who quit less than 10 years prior or 2) having a PLCOm2012 model 6-year risk for lung cancer incidence over 2.6%.
- •Willingness and ability to comply with scheduled visits, laboratory tests, and other trial procedures
- •Written informed consent obtained prior to performing any protocol-related procedures
- •The participant should be affiliated to a social security system
排除标准
- •used for the lung cancer screening implementation study/ TIDL Study:
- •Recent abnormal pulmonary findings under work-up of standard care
- •Having had chest CT <1 year before potential entry into the study
- •Current or prior history of lung cancer, renal cancer, melanoma or breast cancer
- •Inability to provide signed informed consent
- •Insufficient understanding of the languages in which trial information is available
- •Psychiatric or other disorders that are incompatible with compliance to the protocol requirements and follow-up
- •Unable to be followed-up for at least 5-years
- •Body weight >140 Kg because of difficulty of conducting the CT exam
- •Inclusion Criteria used for the ACE 5 Study:
- •Participants from the TIDL Study with non-contrast, non-cardiac chest CT images available as part of the implementation lung cancer screening study
- •Signed consent for cardiovascular add on-study and agree to protocol, including follow-up visit 1-year after the baseline examination
- •Exclusion Criteria used for the ACE 5 Study:
- •Any surgical or medical condition, including short life-expectancy, based on medical records or clinical findings prior to randomization, that will impair the ability of the patient to participate in the study
- •Patients unwilling or unable to comply with the protocol
- •History of non-compliance to medical management and patients who are considered potentially unreliable, based on information obtained prior to randomization
- •History or evidence of alcohol or drug abuse with the last 12 months, based on information obtained prior to randomization, that will influence study participation
结局指标
主要结局
Number of people reaching treatment goals or started new GDMT for smoking, lipid concentrations, blood pressure, and HbA1c
时间窗: 12 months from the baseline visit
To determine whether a Lung Cancer Screening Plus Program in individuals with heavy smoking history improves cardiovascular risk profile, defined as reaching treatment goals or started new GDMT for smoking, lipid concentrations, blood pressure, and HbA1c, compared to the current strategy/standard care. Treatment targets are defined as following: 1. LDL cholesterol \< 1.4 or started treatment with statin and/or ezetimibe after baseline visit 2. Blood pressure \<130/80 or started new antihypertensive therapy after baseline visit 3. No smoking 4. HbA1c \< 52 mmol/L or started new antidiabetic therapy after baseline visit
次要结局
- Number of people with lipid lowering treatment, antihypertensive treatment and antidiabetic treatment at 12 months(12 months from the baseline visit)
- Activity quotient at 12 months post the baseline visit(12 months after the baseline visit)
- Prevalence of smoking at 12 months post the baseline visit(12 months from the baseline visit)
- Blood lipid concentrations at 12 months post the baseline visit(12 months after the baseline visit)
- Blood pressure at 12 months post the baseline visit(12 months after the baseline visit)
- HbA1c concentrations at 12 months post the baseline visit(12 months after the baseline visit)
- Rate of adherence to guideline directed medical therapy for ASCVD at 12 months post the baseline visit(12 months after the baseline visit)
- Quality-of-life (EQ-5D-5L) at 12 months post the baseline visit(12 months after the baseline visit)
- Glomerular filtration rate at 12 months post the baseline visit(12 months after the baseline visit)
- Time to the first event (either [1] any atherosclerotic cardiovascular event or intervention, or [2] non-cancer-related mortality)(Data will be reported at the 1 year follow-up, and at 5 years, 8 years, 10 years, 13 years, and 15 years for secondary endpoints.)
- Time to non-cancer-related mortality(Data will be reported at the 1 year follow-up, and at 5 years, 8 years, 10 years, 13 years, and 15 years for secondary endpoints.)
- Time to all-cause mortality(Data will be reported at the 1 year follow-up, and at 5 years, 8 years, 10 years, 13 years, and 15 years for secondary endpoints.)
- Time to any cardiovascular event or intervention(Data will be reported at the 1 year follow-up, and at 5 years, 8 years, 10 years, 13 years, and 15 years for secondary endpoints.)
- Total number of any cardiovascular events or interventions(Data will be reported at the 1 year follow-up, and at 5 years, 8 years, 10 years, 13 years, and 15 years for secondary endpoints.)
- Total number of coronary events or interventions(Data will be reported at the 1 year follow-up, and at 5 years, 8 years, 10 years, 13 years, and 15 years for secondary endpoints.)
- Difference in total cost(Data will be reported at the 1 year follow-up, and at 5 years, 8 years, 10 years, 13 years, and 15 years for secondary endpoints.)
- Cost-utility(Data will be reported at the 1 year follow-up, and at 5 years, 8 years, 10 years, 13 years, and 15 years for secondary endpoints.)
研究者
Helge Rørvik Røsjø
Professor
University Hospital, Akershus