Efficacy and Safety of Comprehensive Treatment in Patients With Inflammation-associated Rapidly-progressive Coronary Artery Disease (IR-CAD): a Self-controlled Cohort Study
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 39
- 试验地点
- 1
- 主要终点
- Major adverse cardiovascular events (MACE)
研究概览
简要总结
This is a self-controlled cohort study to evaluate the efficacy and safety of comprehensive treatment in patients with inflammation-associated rapidly-progressive coronary artery disease (IR-CAD) by comparing the study endpoints before treatment with those after treatment in the same group of patients.
详细描述
A special type of coronary artery disease (CAD) has been identified in our clinical practice, which has completely different clinical features from those of typical atherosclerotic coronary artery disease (AS-CAD). The patients often have sterile inflammatory diseases and/or clinical evidence of inflammation, whose CAD progresses rapidly, recurs frequently, and responds poorly to intensified secondary prevention of AS-CAD, especially after percutaneous coronary intervention (PCI). We name this special type of CAD inflammation-associated rapidly-progressive coronary artery disease (IR-CAD).
The optimal treatment for IR-CAD remains unknown. We hypothesize that the rapid progression of IR-CAD might be associated with inflammation considering that: 1) inflammation is associated with poor prognosis in CAD patients after PCI; 2) IR-CAD patients often have sterile inflammatory diseases and/or clinical evidence of inflammation; 3) the disease progression of IR-CAD can be controlled to some extent with corticosteroids and immunosuppressive agents. Therefore, we incorporate immunosuppressive therapy into the overall management strategy of IR-CAD patients in clinical practice, developing comprehensive treatment, including: 1) intensified secondary prevention of AS-CAD; 2) immunosuppressive therapy; 3) coronary revascularization; 4) supportive therapies.
The present self-controlled cohort study is designed to evaluate the efficacy and safety of comprehensive treatment in about 39 IR-CAD patients by comparing the outcomes before with those after the initiation of comprehensive treatment in the same group of patients.
All patients who were admitted to the Department of Cardiology, Peking Union Medical College Hospital on and after January 1, 2022 will be screened for study participation. Patients were diagnosed as IR-CAD if they presented with 1) rapidly progressive myocardial ischemia (typical symptoms and non-invasive evidence) despite standard treatment for secondary prevention of AS-CAD after the last coronary revascularization; 2) angiographic evidence of new coronary lesions (de novo stenosis or restenosis) related to myocardial ischemia; 3) evidence of inflammation (positive inflammation markers or established diagnoses of inflammatory diseases or use of immunosuppressive therapy). IR-CAD patients who have received comprehensive treatment will be enrolled in the present cohort study. The eligible patients will be followed for 24 months since the initiation of comprehensive treatment.
The primary efficacy endpoint is major adverse cardiovascular events (MACE). The key secondary efficacy endpoint is target vessel related major adverse cardiovascular events (TV-MACE). Other secondary efficacy endpoints include individual components of MACE and TV-MACE, exercise capacity, angiographic metrics of coronary lesions, and inflammation markers. The safety endpoints are major bleeding events and severe infection events.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Fulfilling all the following criteria before initiation of comprehensive treatment:
- •1.1 18 years of age or older, male or female.
- •1.2 Negative result of urine or blood pregnancy test for females with childbearing potential (not post-menopausal or surgically sterile).
- •1.3 Prior history of coronary revascularization (percutaneous coronary intervention [PCI] or coronary artery bypass graft [CABG]).
- •1.4 Receiving standard treatment for secondary prevention of atherosclerotic coronary artery disease (AS-CAD) after the last coronary revascularization.
- •1.5 Hospitalization due to rapidly-progressive myocardial ischemia:
- •Typical symptoms of angina (Canadian Cardiovascular Society [CCS] III-IV) and non-invasive evidence of myocardial ischemia; and
- •Occurred within 6 months or occurred on immunosuppressive therapy within 12 months of the last coronary revascularization.
- •1.6 Angiographic evidence of new coronary lesions (de novo stenoses or restenoses):
- •Occurred after the last coronary revascularization; and
- •Related to myocardial ischemia (location, extent, severity, et al).
- •1.7 Evidence of inflammation:
- •At least one of the markers indicating active inflammation has ever been elevated (erythrocyte sedimentation rate [ESR], high-sensitivity C-reactive protein [hs-CRP], interleukin [IL]-6, tumor necrosis factor [TNF]-α, ferritin, et al); or
- •Established diagnosis of systemic autoimmune disease or systemic vasculitis; or
- •Receiving immunosuppressive therapy.
- •Receiving comprehensive treatment, including ischemia-driven PCI which was performed no earlier than 40 days of the initiation of immunosuppressive therapy.
排除标准
- •Coronary restenosis due to mechanical factors (stent under-expansion, stent mal-apposition, stent rupture, et al).
- •Other moderate to severe heart diseases (congenital heart disease, valvular heart disease, myocarditis, cardiomyopathy, pericardial diseases, pulmonary hypertension, heart failure, arrhythmia, et al).
- •Active acute or chronic infection (human immunodeficiency virus [HIV], tuberculosis, et al).
- •Active malignancy (diagnosed within 12 months or with ongoing requirement for treatment).
- •Vital organ failure.
- •Life expectancy < 1 year.
- •Contraindications for or intolerance to treatment for secondary prevention of AS-CAD, contrast agents, glucocorticoids, immunosuppressive agents.
- •In pregnancy or breast-feeding, or with intention to be pregnant during the study period.
- •Risk of non-compliance (history of drug addiction or alcohol abuse, et al).
- •Previous enrollment in this study.
- •Participation in another study within 30 days.
- •Involvement in the planning and conduct of this study (applying to investigators, contract research organization staffs, study site staffs, et al).
- •Any condition, which in the opinion of the investigators, would make it unsuitable for the patient to participate in this study.
研究组 & 干预措施
Pre-treatment Group
IR-CAD patients before receiving comprehensive treatment.
干预措施: Healthy life style (Behavioral)
Pre-treatment Group
IR-CAD patients before receiving comprehensive treatment.
干预措施: Secondary prevention for atherosclerotic coronary artery disease (Drug)
Pre-treatment Group
IR-CAD patients before receiving comprehensive treatment.
干预措施: Coronary revascularization (Procedure)
Pre-treatment Group
IR-CAD patients before receiving comprehensive treatment.
干预措施: Supportive therapies (Drug)
Post-treatment Group
IR-CAD patients after receiving comprehensive treatment.
干预措施: Healthy life style (Behavioral)
Post-treatment Group
IR-CAD patients after receiving comprehensive treatment.
干预措施: Secondary prevention for atherosclerotic coronary artery disease (Drug)
Post-treatment Group
IR-CAD patients after receiving comprehensive treatment.
干预措施: Immunosuppressive therapy (Drug)
Post-treatment Group
IR-CAD patients after receiving comprehensive treatment.
干预措施: Coronary revascularization (Procedure)
Post-treatment Group
IR-CAD patients after receiving comprehensive treatment.
干预措施: Supportive therapies (Drug)
结局指标
主要结局
Major adverse cardiovascular events (MACE)
时间窗: Time from the last coronary revascularization to the first occurrence of MACE, or the last follow-up visit, or the end of 24-month follow-up, which occurs first, both before and after the initiation of comprehensive treatment.
The composite endpoint including death, or Q wave myocardial infarction, or unplanned myocardial ischemia-driven coronary revascularization (PCI or CABG), or unplanned myocardial ischemia-driven hospitalization.
次要结局
- Target vessel related unplanned myocardial ischemia-driven coronary revascularization(Time from the last coronary revascularization to the first occurrence of MACE, or the last follow-up visit, or the end of 24-month follow-up, which occurs first, both before and after the initiation of comprehensive treatment.)
- Birmingham vasculitis activity score(Before treatment: the timepoint before the initiation of comprehensive treatment, or at baseline. After treatment: the timepoint of the first occurrence of MACE, or the last follow-up visit, or the end of 24-month follow-up, which occurs first.)
- Target vessel related major adverse cardiovascular events (TV-MACE)(Time from the last coronary revascularization to the first occurrence of MACE, or the last follow-up visit, or the end of 24-month follow-up, which occurs first, both before and after the initiation of comprehensive treatment.)
- Myocardial infarction(Time from the last coronary revascularization to the first occurrence of MACE, or the last follow-up visit, or the end of 24-month follow-up, which occurs first, both before and after the initiation of comprehensive treatment.)
- Unplanned myocardial ischemia-driven hospitalization(Time from the last coronary revascularization to the first occurrence of MACE, or the last follow-up visit, or the end of 24-month follow-up, which occurs first, both before and after the initiation of comprehensive treatment.)
- Target vessel related unplanned myocardial ischemia-driven hospitalization(Time from the last coronary revascularization to the first occurrence of MACE, or the last follow-up visit, or the end of 24-month follow-up, which occurs first, both before and after the initiation of comprehensive treatment.)
- Walking distance in 6 minutes(Before treatment: the timepoint before the initiation of comprehensive treatment, or at baseline. After treatment: the timepoint of the first occurrence of MACE, or the last follow-up visit, or the end of 24-month follow-up, which occurs first.)
- Target lesion minimal lumen area (TL-MLA)(Before treatment: the timepoint before the initiation of comprehensive treatment, or at baseline. After treatment: the timepoint of the first occurrence of MACE, or the last follow-up visit, or the end of 24-month follow-up, which occurs first.)
- Number of vessel segments with coronary lesions(Before treatment: the timepoint before the initiation of comprehensive treatment, or at baseline. After treatment: the timepoint of the first occurrence of MACE, or the last follow-up visit, or the end of 24-month follow-up, which occurs first.)
- Erythrocyte sedimentation rate (ESR)(Before treatment: the timepoint before the initiation of comprehensive treatment, or at baseline. After treatment: the timepoint of the first occurrence of MACE, or the last follow-up visit, or the end of 24-month follow-up, which occurs first.)
- Target lesion percent area stenosis (TL-%AS)(Before treatment: the timepoint before the initiation of comprehensive treatment, or at baseline. After treatment: the timepoint of the first occurrence of MACE, or the last follow-up visit, or the end of 24-month follow-up, which occurs first.)
- High-sensitivity C-reactive protein (hs-CRP)(Before treatment: the timepoint before the initiation of comprehensive treatment, or at baseline. After treatment: the timepoint of the first occurrence of MACE, or the last follow-up visit, or the end of 24-month follow-up, which occurs first.)
- Tumor necrosis factor (TNF)-α(Before treatment: the timepoint before the initiation of comprehensive treatment, or at baseline. After treatment: the timepoint of the first occurrence of MACE, or the last follow-up visit, or the end of 24-month follow-up, which occurs first.)
- Target vessel related myocardial infarction(Time from the last coronary revascularization to the first occurrence of MACE, or the last follow-up visit, or the end of 24-month follow-up, which occurs first, both before and after the initiation of comprehensive treatment.)
- Unplanned myocardial ischemia-driven coronary revascularization(Time from the last coronary revascularization to the first occurrence of MACE, or the last follow-up visit, or the end of 24-month follow-up, which occurs first, both before and after the initiation of comprehensive treatment.)
- SYNTAX score(Before treatment: the timepoint before the initiation of comprehensive treatment, or at baseline. After treatment: the timepoint of the first occurrence of MACE, or the last follow-up visit, or the end of 24-month follow-up, which occurs first.)
- Death(Time from the last coronary revascularization to the first occurrence of MACE, or the last follow-up visit, or the end of 24-month follow-up, which occurs first, both before and after the initiation of comprehensive treatment.)
- Number of squats in 1 minute(Before treatment: the timepoint before the initiation of comprehensive treatment, or at baseline. After treatment: the timepoint of the first occurrence of MACE, or the last follow-up visit, or the end of 24-month follow-up, which occurs first.)
- interleukin (IL)-6(Before treatment: the timepoint before the initiation of comprehensive treatment, or at baseline. After treatment: the timepoint of the first occurrence of MACE, or the last follow-up visit, or the end of 24-month follow-up, which occurs first.)
研究者
LiuZhenyu
Professor
Peking Union Medical College Hospital