Clinical trial NCT05860400: Efficacy and Safety of Comprehensive Treatment in Patients with IR-CAD: a Self-controlled Cohort Study
Official title: Efficacy and Safety of Comprehensive Treatment in Patients with Inflammation-associated Rapidly-progressive Coronary Artery Disease (IR-CAD): a Self-controlled Cohort Study
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Coronary Artery Disease
Coronary Artery Stenosis
Coronary Artery Restenosis
Coronary Artery Disease Progression
Inflammation
Inflammatory Disease
Inflammation Vascular
Keywords: Coronary Artery Disease
Coronary Revascularization
Progression, Disease
Inflammation
Lead sponsor: Peking Union Medical College Hospital
Sponsor class: OTHER
First posted: 2023-05-16
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 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.

Brief summary: 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.

Detailed description: 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.

For endpoints which are categorical variables, e.g., MACE, survival analysis will be used to compare the survival curves before treatment (from the last coronary revascularization before the initiation of comprehensive treatment to the first occurrence of MACE) with those after treatment (from the initiation of comprehensive treatment to the first occurrence of MACE, or the last follow-up visit, or the end of 24-month follow-up, which occurs first). Event-free survival rates and relative risk will be calculated.

For endpoints which are continuous variables, e.g., inflammation markers, paired t-test or paired rank sum test will be used to compare the endpoint levels before treatment (before the initiation of comprehensive treatment or at baseline) with those after treatment (the first occurrence of MACE, or the last follow-up visit, or the end of 24-month follow-up, which occurs first, after the initiation of comprehensive treatment).

Eligibility criteria: Inclusion Criteria:

1. 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.
2. Receiving comprehensive treatment, including ischemia-driven PCI which was performed no earlier than 40 days of the initiation of immunosuppressive therapy.

Exclusion Criteria:

1. Coronary restenosis due to mechanical factors (stent under-expansion, stent mal-apposition, stent rupture, et al).
2. Other moderate to severe heart diseases (congenital heart disease, valvular heart disease, myocarditis, cardiomyopathy, pericardial diseases, pulmonary hypertension, heart failure, arrhythmia, et al).
3. Active acute or chronic infection (human immunodeficiency virus \[HIV\], tuberculosis, et al).
4. Active malignancy (diagnosed within 12 months or with ongoing requirement for treatment).
5. Vital organ failure.
6. Life expectancy \< 1 year.
7. Contraindications for or intolerance to treatment for secondary prevention of AS-CAD, contrast agents, glucocorticoids, immunosuppressive agents.
8. In pregnancy or breast-feeding, or with intention to be pregnant during the study period.
9. Risk of non-compliance (history of drug addiction or alcohol abuse, et al).
10. Previous enrollment in this study.
11. Participation in another study within 30 days.
12. Involvement in the planning and conduct of this study (applying to investigators, contract research organization staffs, study site staffs, et al).
13. Any condition, which in the opinion of the investigators, would make it unsuitable for the patient to participate in this study.

Primary outcomes:
measure: Major adverse cardiovascular events (MACE)
timeFrame: 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.
Secondary outcomes:
measure: Target vessel related major adverse cardiovascular events (TV-MACE)
timeFrame: 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.
measure: Death
timeFrame: 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.
measure: Myocardial infarction
timeFrame: 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.
measure: Target vessel related myocardial infarction
timeFrame: 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.
measure: Unplanned myocardial ischemia-driven coronary revascularization
timeFrame: 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.
measure: Target vessel related unplanned myocardial ischemia-driven coronary revascularization
timeFrame: 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.
measure: Unplanned myocardial ischemia-driven hospitalization
timeFrame: 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.
measure: Target vessel related unplanned myocardial ischemia-driven hospitalization
timeFrame: 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.
measure: Walking distance in 6 minutes
timeFrame: 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.
measure: Number of squats in 1 minute
timeFrame: 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.
measure: Target lesion minimal lumen area (TL-MLA)
timeFrame: 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.
measure: Target lesion percent area stenosis (TL-%AS)
timeFrame: 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.
measure: SYNTAX score
timeFrame: 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.
measure: Number of vessel segments with coronary lesions
timeFrame: 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.
measure: Erythrocyte sedimentation rate (ESR)
timeFrame: 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.
measure: High-sensitivity C-reactive protein (hs-CRP)
timeFrame: 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.
measure: interleukin (IL)-6
timeFrame: 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.
measure: Tumor necrosis factor (TNF)-α
timeFrame: 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.
measure: Birmingham vasculitis activity score
timeFrame: 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.
Other outcomes:
measure: Major bleeding events
timeFrame: 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.
measure: Severe infection events
timeFrame: 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.
Locations:
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
Study officials:
affiliation: Peking Union Medical College Hospital
name: Zhenyu Liu, M.D.
role: PRINCIPAL_INVESTIGATOR
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