The Low-Dose Interleukin-2 For The Reduction Of Vascular Inflammation In Acute Coronary Syndromes -Clinical Outcomes And Follow-up Study
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Major adverse cardiovascular outcomes
研究概览
简要总结
The preceding IVORY trial (NCT04241601) has completed. As atherosclerosis and its complications are driven by inflammation the investigators hypothesise that treatment with low-dose IL2 may reduce adverse cardiovascular outcomes compared to placebo.
In this follow-up study, the investigators aim to collect cardiovascular clinical outcome data for patients who completed the IVORY clinical trial and will look at major adverse cardiovascular events (MACE), defined as cardiovascular death, non-fatal myocardial infarction, resuscitated cardiac arrest, ischaemic stroke, or unplanned coronary revascularization. In addition, data on adverse events such as all cause death, haemorrhagic stroke, new atrial fibrillation, ventricular arrhythmias, hospitalisation due to cardiovascular causes (e.g. stable and unstable angina, TIAs, heart failure), amputations and revascularisation due to peripheral vascular disease.
详细描述
A heart attack occurs when there is reduced blood flow to heart muscle cells which results from narrowings or blockages in walls of blood vessels supplying the heart, due to fatty deposits and inflammatory cells that build up over time. This build-up leads to heart muscle damage called a heart attack.
The immune system plays an important role in both the development of the narrowings and the damage to the heart muscle during a heart attack. Studies have shown that there is a lower level of protective immune cells called regulatory T-cells (Tregs) in heart attack patients. Increasing the number of circulating Tregs may have a direct effect in reducing the inflammation in arteries, preventing further narrowings in blood vessels and improving heart muscle function. Aldesleukin, also known as interleukin-2 (IL2), is a medicine that stimulates the production of Treg cells when given at low doses. The effectiveness of IL2 in influencing the immune system was tested in a phase 2 trial, IVORY.
Participants were recruited to the IVORY trial following a sudden narrowing/blockages in walls of blood vessels to the heart resulting in a heart attack (Acute Coronary Syndrome (ACS)). Participants were randomised to receive either low dose IL2 or placebo, researchers and participants were blinded to the treatment allocation. Participants underwent two PET/CT (Positron emission tomography-computed tomography) scans to observe change of inflammation in the blood vessels from baseline between the two trial groups.
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 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants who completed the full per-protocol treatment regime of low-dose IL2 or placebo having attended the final dosing visit in the IVORY trial. IVORY patients who previously consented to have their medical records inspected in the IVORY trial and who have already passed away at the commencement of IVORY-FINALE will also be included in analyses
排除标准
- •Patients who decline participation
- •Patients who did not consent to being contacted about future research
- •Patients who were withdrawn from the IVORY trial for any reason
研究组 & 干预措施
Aldesleukin
Aldesleukin loading dose 1.5 x 10^6 IU followed by maintenance dose of 1.5 x 10^6 IU
干预措施: Aldesleukin (Drug)
Placebo
Dextrose 5%
干预措施: Dextrose 5% in water (Drug)
结局指标
主要结局
Major adverse cardiovascular outcomes
时间窗: 5 years from when initially dosed in preceding IVORY trial
Number of major adverse cardiovascular outcomes
次要结局
- Deaths due to cardiovascular causes comparing IL2 to placebo(5 years from when initially dosed in preceding IVORY trial)
- Unplanned coronary vascularisations comparing IL2 to placebo(5 years from when initially dosed in preceding IVORY trial)
- Resuscitated cardiac arrests comparing IL2 to placebo(5 years from when initially dosed in preceding IVORY trial)
- Non-fatal MI (including NSTEMI and STEMI) comparing IL2 to placebo(5 years from when initially dosed in preceding IVORY trial)
- Hospitalisations due to symptoms from heart failure (incl admission due to pulmonary oedema and congestive heart failure) comparing IL2 to placebo(5 years from when initially dosed in preceding IVORY trial)
- Revascularisations for peripheral vascular disease comparing IL2 to placebo(5 years from when initially dosed in preceding IVORY trial)
- Amputations due to peripheral vascular disease comparing IL2 to placebo(5 years from when initially dosed in preceding IVORY trial)
- Haemorrhagic strokes comparing IL2 to placebo(5 years from when initially dosed in preceding IVORY trial)
- New atrial fibrillation diagnosis comparing IL2 to placebo(5 years from when initially dosed in preceding IVORY trial)
- Ventricular arrhythmia (sustained ventricular tachycardia and ventricular fibrillation) comparing IL2 to placebo(5 years from when initially dosed in preceding IVORY trial)
- Ischaemic strokes comparing IL2 to placebo(5 years from when initially dosed in preceding IVORY trial)
- Death due to cardiovascular causes(1 year from when initially dosed in preceding IVORY trial)
- Hospitalisations due to cardiovascular causes comparing IL2 to placebo(5 years from when initially dosed in preceding IVORY trial)
- All-cause deaths comparing IL2 to placebo(1 year from when initially dosed in preceding IVORY trial)
- All-cause death comparing IL2 to placebo(5 years from when initially dosed in preceding IVORY trial)
研究者
Joseph Cheriyan, MBChB, MA, FRCP, FESC, FACC
Dr Joseph Cheriyan, Consultant Clinical Pharmacologist/Affilitated Associate Professor
Cambridge University Hospitals NHS Foundation Trust