ESCALATion of Medical Therapy Following Multimodality Plaque Evaluation in High-risk Chronic Coronary Syndromes
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 50
- 主要终点
- Absolute change in minimal fibrous cap thickness
研究概览
简要总结
ESCALATE will provide a thorough investigation of how anti-inflammatory therapy, with low-dose colchicine, affects patients with stable coronary artery disease. Using traditional clinical risk factors and multimodality intracoronary imaging, the investigators will identify patients with the greatest clinical risk.
Participants will undergo repeat multimodality intracoronary imaging assessment at 6 months to measure the impact once-daily low-dose colchicine therapy on the structure and function of coronary arteries.
This study will provide valuable insights into how anti-inflammatory therapies, such as colchicine, may improve outcomes in patients with coronary artery disease.
详细描述
- Background and study aims
Despite recent advances, coronary artery disease (CAD) remains the main cause of death worldwide. CAD occurs when the arteries bringing blood to the heart become narrowed by a build-up of fatty material within their walls. If this occurs gradually, it can cause chest discomfort i.e., angina. In a heart attack, the artery wall becomes inflamed and splits causing blood clot formation and an abrupt blockage of flow, resulting in severe pain and damaged heart muscle.
Current treatments focus on reducing cholesterol, slowing the build-up of fatty material, and rapidly restoring blood flow during a heart attack. Chronic inflammation, acting in tandem with other risk factors, has been identified as playing a central role in CAD progression and its acute manifestations.
Colchicine is a safe, well-tolerated, anti-inflammatory therapy used in the treatment of gout and other inflammatory conditions. Daily treatment with low-dose colchicine has proven effective in reducing rates of heart attack and death in large clinical trials, but use in routine practice remains low. A contributing factor to this reticence is uncertainty regarding the mechanism through which colchicine provides benefit. This study is designed to address this knowledge gap. 2. Who can participate?
Patients aged 18 to 90 years old with coronary artery disease and high clinical risk 3. What does the study involve?
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Ability to provide written informed consent
- •Age 18 to 90 years old
- •Male, or female of non-child-bearing potential
- •Elevated clinical risk, as evidenced by ≥1 of:
- •Previous spontaneous acute myocardial infarction (diagnosed according to the universal MI criteria) with or without persistent ST-segment elevation
- •Previous stroke or intervention for peripheral arterial disease (i.e., evidence of atherosclerotic disease affecting >1 vascular bed)
- •Established diagnosis of diabetes mellitus
- •Systemic Coronary Risk Estimation 2 (SCORE2) or Systemic Coronary Risk Estimation 2 - Older Persons (SCORE2-OP) algorithm 10-year risk of fatal and non-fatal myocardial infarction or stroke >10%
- •Documented evidence of coronary artery disease, with an angiographically moderate stenosis on invasive coronary angiography (30-80%)
- •At least one non-flow limiting (FFR >0.80) moderate lesion with TCFA (minimum fibrous cap thickness of less than or equal to120µm and lipid arc >90°)
- •History of prescribed statin therapy, at a stable dose, for >4 weeks
- •Evidence of residual inflammation at baseline (i.e., high-sensitivity CRP ≥2)
排除标准
- •Women who are pregnant, breast feeding, or of child-bearing potential
- •Symptoms of unstable angina, characterised as: angina at rest; new onset of severe exertional angina (CCS grade III or higher for <4 weeks); or distinct, sudden, intensification of previously stable angina
- •Previous spontaneous acute myocardial infarction (diagnosed according to the universal MI criteria) with or without persistent ST-segment elevation <4 weeks from recruitment
- •Previous coronary artery bypass grafting
- •Known chronic total occlusion of coronary artery
- •Chronic kidney disease with eGFR <50 mL/min/1.73 m2 per MDRD formula or renal replacement therapy at baseline assessment
- •Known active or recurrent hepatic disorder (including cirrhosis, hepatitis B and hepatitis C, or confirmed ALT/AST levels > 3 times ULN or total bilirubin > 2 times ULN) at baseline assessment
- •Symptoms of severe heart failure (systolic or diastolic) with New York Heart Association (NYHA) Functional Classification 3 or 4
- •Moderate or severe valvular heart disease considered likely to require intervention
- •History of blood dyscrasia including anaemia, thrombocytopenia, neutrophilia, leukopenia or other abnormality of blood count at baseline
- •Peripheral neuritis, myositis or marked myo-sensitivity to statins
- •A history of alcohol and/or substance abuse that could interfere with the conduct of the trial
- •Patients with suspected or proven immunocompromised state, including:
- •those with evidence of Human Immunodeficiency Virus (HIV) infection; Patients on anti-retroviral therapy are excluded
- •those with any other medical condition which in the opinion of the investigator places the patient at unacceptable risk for participation in immunomodulatory therapy
- •History of hypersensitivity to the study drug or its constituents
- •Patients who have received an investigational drug or device within 30 days (inclusive) of baseline assessment, or who are expected to participate in any other investigational drug or device study during the conduct of this trial
- •Any biologic drugs targeting the immune system (for example, TNF blockers, anakinra, rituximab, abatacept, tocilizumab)
- •Established long-term pharmacotherapy with a strong CYP3A4 inhibitor or a P-glycoprotein inhibitor (P-gpi) (e.g., macrolide antibiotics, ciclosporin, ketoconazole, itraconazole, voriconazole, HIV protease inhibitors, verapamil, diltiazem and disulfiram)
- •Contraindications to intravenous adenosine will exclude patients from adenosine induced hyperaemia
- •Any life-threatening condition with life expectancy <6 months that might prevent the patient from completing the study.
研究组 & 干预措施
Low dose colchicine 0.5mg OD
Low dose colchicine 0.5mg OD for 6 months
干预措施: Colchicine 0.5 MG (Drug)
结局指标
主要结局
Absolute change in minimal fibrous cap thickness
时间窗: 6months
The absolute change (µm) in minimal fibrous cap thickness, in a defined arterial region of interest, as assessed by OCT
次要结局
- % change in maximal lipid arc(6 months)
- Absolute and percentage change in vessel fractional flow reserve (FFR)(6 months)
- Major adverse clinical events(6 months)
- Percentage change in lipid index(6 months)
- Absolute change in maximum lipid core burden index in a 4-mm segment (maxLCBI4mm)(6 months)
- Percentage change in high-sensitivity c-reactive protein (hs-CRP)(6 months)
- Acute kidney injury(6 months)
- Major bleeding events (BARC 3-5)(6 months)
- Absolute and percentage change in coronary flow reserve (CFR)(6 months)
- Hospitalisation with serious infection(6 months)
- % change in minimal fibrous cap thickness(6 months)
- Relative change (%) in maximum lipid core burden index in a 4-mm segment (maxLCBI4mm)(6 months)
- Change in total atheroma volume(6 months)
- Absolute and percentage change in index of microvascular resistance (IMR)(6 months)