Clinical trial NCT06427694: Low-Dose IL-2 For The Reduction Of Vascular Inflammation In ACS -Clinical Outcomes & Follow-up Study
Official title: The Low-Dose Interleukin-2 For The Reduction Of Vascular Inflammation In Acute Coronary Syndromes -Clinical Outcomes And Follow-up Study
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Acute Coronary Syndromes
Keywords: Acute Coronary Syndromes
Lead sponsor: Cambridge University Hospitals NHS Foundation Trust
Sponsor class: OTHER
First posted: 2024-05-24
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Participants of the IVORY trial (NCT04241601) and who consented to be contacted for future research received all scheduled doses of either placebo or IL2 and are alive at the time of data collection will be approached.

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Major adverse cardiovascular outcomes
timeFrame: 1 year from when initially dosed in preceding IVORY trial
measure: Major adverse cardiovascular outcomes
timeFrame: 2 years from when initially dosed in preceding IVORY trial
measure: Major adverse cardiovascular outcomes
timeFrame: 5 years from when initially dosed in preceding IVORY trial
Secondary outcomes:
measure: Death due to cardiovascular causes
timeFrame: 1 year from when initially dosed in preceding IVORY trial
measure: Deaths due to cardiovascular causes comparing IL2 to placebo
timeFrame: 2 years from when initially dosed in preceding IVORY trial
measure: Deaths due to cardiovascular causes comparing IL2 to placebo
timeFrame: 5 years from when initially dosed in preceding IVORY trial
measure: Resuscitated cardiac arrests comparing IL2 to placebo
timeFrame: 1 year from when initially dosed in preceding IVORY trial
measure: Resuscitated cardiac arrests comparing IL2 to placebo
timeFrame: 2 years from when initially dosed in preceding IVORY trial
measure: Resuscitated cardiac arrests comparing IL2 to placebo
timeFrame: 5 years from when initially dosed in preceding IVORY trial
measure: Non-fatal MI (including NSTEMI and STEMI) comparing IL2 to placebo
timeFrame: 1 year from when initially dosed in preceding IVORY trial
measure: Non-fatal MI (including NSTEMI and STEMI) comparing IL2 to placebo
timeFrame: 2 years from when initially dosed in preceding IVORY trial
measure: Non-fatal MI (including NSTEMI and STEMI) comparing IL2 to placebo
timeFrame: 5 years from when initially dosed in preceding IVORY trial
measure: Ischaemic strokes comparing IL2 to placebo
timeFrame: 1 year from when initially dosed in preceding IVORY trial
measure: Ischaemic strokes comparing IL2 to placebo
timeFrame: 2 years from when initially dosed in preceding IVORY trial
measure: Ischaemic strokes comparing IL2 to placebo
timeFrame: 5 years from when initially dosed in preceding IVORY trial
measure: Unplanned coronary vascularisations comparing IL2 to placebo
timeFrame: 1 year from when initially dosed in preceding IVORY trial
measure: Unplanned coronary vascularisations comparing IL2 to placebo
timeFrame: 2 years from when initially dosed in preceding IVORY trial
measure: Unplanned coronary vascularisations comparing IL2 to placebo
timeFrame: 5 years from when initially dosed in preceding IVORY trial
measure: Hospitalisations due to cardiovascular causes comparing IL2 to placebo
timeFrame: 1 year from when initially dosed in preceding IVORY trial
measure: Hospitalisations due to cardiovascular causes comparing IL2 to placebo
timeFrame: 2 years from when initially dosed in preceding IVORY trial
measure: Hospitalisations due to cardiovascular causes comparing IL2 to placebo
timeFrame: 5 years from when initially dosed in preceding IVORY trial
measure: All-cause deaths comparing IL2 to placebo
timeFrame: 1 year from when initially dosed in preceding IVORY trial
measure: All-cause death comparing IL2 to placebo
timeFrame: 2 years from when initially dosed in preceding IVORY trial
measure: All-cause death comparing IL2 to placebo
timeFrame: 5 years from when initially dosed in preceding IVORY trial
measure: Hospitalisations due to symptoms from heart failure (incl admission due to pulmonary oedema and congestive heart failure) comparing IL2 to placebo
timeFrame: 1 year from when initially dosed in preceding IVORY trial
measure: Hospitalisations due to symptoms from heart failure (incl admission due to pulmonary oedema and congestive heart failure) comparing IL2 to placebo
timeFrame: 2 years from when initially dosed in preceding IVORY trial
measure: Hospitalisations due to symptoms from heart failure (incl admission due to pulmonary oedema and congestive heart failure) comparing IL2 to placebo
timeFrame: 5 years from when initially dosed in preceding IVORY trial
measure: Revascularisations for peripheral vascular disease comparing IL2 to placebo
timeFrame: 1 year from when initially dosed in preceding IVORY trial
measure: Revascularisations for peripheral vascular disease comparing IL2 to placebo
timeFrame: 2 years from when initially dosed in preceding IVORY trial
measure: Revascularisations for peripheral vascular disease comparing IL2 to placebo
timeFrame: 5 years from when initially dosed in preceding IVORY trial
measure: Amputations due to peripheral vascular disease comparing IL2 to placebo
timeFrame: 1 year from when initially dosed in preceding IVORY trial
measure: Amputations due to peripheral vascular disease comparing IL2 to placebo
timeFrame: 2 years from when initially dosed in preceding IVORY trial
measure: Amputations due to peripheral vascular disease comparing IL2 to placebo
timeFrame: 5 years from when initially dosed in preceding IVORY trial
measure: Haemorrhagic strokes comparing IL2 to placebo
timeFrame: 1 year from when initially dosed in preceding IVORY trial
measure: Haemorrhagic strokes comparing IL2 to placebo
timeFrame: 2 years from when initially dosed in preceding IVORY trial
measure: Haemorrhagic strokes comparing IL2 to placebo
timeFrame: 5 years from when initially dosed in preceding IVORY trial
measure: New atrial fibrillation diagnosis comparing IL2 to placebo
timeFrame: 1 year from when initially dosed in preceding IVORY trial
measure: New atrial fibrillation diagnosis comparing IL2 to placebo
timeFrame: 2 years from when initially dosed in preceding IVORY trial
measure: New atrial fibrillation diagnosis comparing IL2 to placebo
timeFrame: 5 years from when initially dosed in preceding IVORY trial
measure: Ventricular arrhythmia (sustained ventricular tachycardia and ventricular fibrillation) comparing IL2 to placebo
timeFrame: 1 year from when initially dosed in preceding IVORY trial
measure: Ventricular arrhythmia (sustained ventricular tachycardia and ventricular fibrillation) comparing IL2 to placebo
timeFrame: 2 years from when initially dosed in preceding IVORY trial
measure: Ventricular arrhythmia (sustained ventricular tachycardia and ventricular fibrillation) comparing IL2 to placebo
timeFrame: 5 years from when initially dosed in preceding IVORY trial
Other outcomes:
Locations:
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
state: Cambridgeshire
Study officials:
affiliation: Cambridge University Hospitals NHS Foundation Trust
name: Joseph Cheriyan, MBChB, FRCP
role: PRINCIPAL_INVESTIGATOR
References: