Low-Dose IL-2 For The Reduction Of Vascular Inflammation In ACS -Clinical Outcomes & Follow-up Study

Acute Coronary Syndromes Clinical Trial

— IVORY-FINALE  

Official title:

The Low-Dose Interleukin-2 For The Reduction Of Vascular Inflammation In Acute Coronary Syndromes -Clinical Outcomes And Follow-up Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06427694
• Other study ID #: IVORY-FINALE (A096877)
• Secondary ID: 339102
• Status: Recruiting
• Start date: June 1, 2024
• Est. completion date: February 11, 2030

Study information

• Verified date: June 2024
• Source: Cambridge University Hospitals NHS Foundation Trust
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: February 11, 2030
• Est. primary completion date: April 30, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Coronary Syndrome
• Acute Coronary Syndromes
• Inflammation
• Syndrome

Intervention

Drug:
• Aldesleukin
IL2 antagonist
• Dextrose 5% in water
matched placebo to active

Locations

Country	Name	City	State
United Kingdom	Addenbrooke's Hospital	Cambridge	Cambridgeshire

Sponsors (1)

Lead Sponsor	Collaborator
Cambridge University Hospitals NHS Foundation Trust

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Major adverse cardiovascular outcomes	Number of major adverse cardiovascular outcomes	1 year from when initially dosed in preceding IVORY trial
Primary	Major adverse cardiovascular outcomes	Number of major adverse cardiovascular outcomes	2 years from when initially dosed in preceding IVORY trial
Primary	Major adverse cardiovascular outcomes	Number of major adverse cardiovascular outcomes	5 years from when initially dosed in preceding IVORY trial
Secondary	Death due to cardiovascular causes	Number of deaths due to cardiovascular causes comparing IL2 to placebo	1 year from when initially dosed in preceding IVORY trial
Secondary	Deaths due to cardiovascular causes comparing IL2 to placebo	Number of deaths due to cardiovascular causes comparing IL2 to placebo	2 years from when initially dosed in preceding IVORY trial
Secondary	Deaths due to cardiovascular causes comparing IL2 to placebo	Number of deaths due to cardiovascular causes comparing IL2 to placebo	5 years from when initially dosed in preceding IVORY trial
Secondary	Resuscitated cardiac arrests comparing IL2 to placebo	Numbers of resuscitated cardiac arrests comparing IL2 to placebo	1 year from when initially dosed in preceding IVORY trial
Secondary	Resuscitated cardiac arrests comparing IL2 to placebo	Numbers of resuscitated cardiac arrests comparing IL2 to placebo	2 years from when initially dosed in preceding IVORY trial
Secondary	Resuscitated cardiac arrests comparing IL2 to placebo	Numbers of resuscitated cardiac arrests comparing IL2 to placebo	5 years from when initially dosed in preceding IVORY trial
Secondary	Non-fatal MI (including NSTEMI and STEMI) comparing IL2 to placebo	Number of non-fatal MI (including NSTEMI and STEMI) comparing IL2 to placebo	1 year from when initially dosed in preceding IVORY trial
Secondary	Non-fatal MI (including NSTEMI and STEMI) comparing IL2 to placebo	Number of non-fatal MI (including NSTEMI and STEMI) comparing IL2 to placebo	2 years from when initially dosed in preceding IVORY trial
Secondary	Non-fatal MI (including NSTEMI and STEMI) comparing IL2 to placebo	Number of non-fatal MI (including NSTEMI and STEMI) comparing IL2 to placebo	5 years from when initially dosed in preceding IVORY trial
Secondary	Ischaemic strokes comparing IL2 to placebo	Number of ischaemic strokes comparing IL2 to placebo	1 year from when initially dosed in preceding IVORY trial
Secondary	Ischaemic strokes comparing IL2 to placebo	Number of ischaemic strokes comparing IL2 to placebo	2 years from when initially dosed in preceding IVORY trial
Secondary	Ischaemic strokes comparing IL2 to placebo	Number of ischaemic strokes comparing IL2 to placebo	5 years from when initially dosed in preceding IVORY trial
Secondary	Unplanned coronary vascularisations comparing IL2 to placebo	Number of unplanned coronary vascularisations comparing IL2 to placebo	1 year from when initially dosed in preceding IVORY trial
Secondary	Unplanned coronary vascularisations comparing IL2 to placebo	Number of unplanned coronary vascularisations comparing IL2 to placebo	2 years from when initially dosed in preceding IVORY trial
Secondary	Unplanned coronary vascularisations comparing IL2 to placebo	Number of unplanned coronary vascularisations comparing IL2 to placebo	5 years from when initially dosed in preceding IVORY trial
Secondary	Hospitalisations due to cardiovascular causes comparing IL2 to placebo	Number of hospitalisations due to cardiovascular causes comparing IL2 to placebo	1 year from when initially dosed in preceding IVORY trial
Secondary	Hospitalisations due to cardiovascular causes comparing IL2 to placebo	Number of hospitalisations due to cardiovascular causes comparing IL2 to placebo	2 years from when initially dosed in preceding IVORY trial
Secondary	Hospitalisations due to cardiovascular causes comparing IL2 to placebo	Number of hospitalisations due to cardiovascular causes comparing IL2 to placebo	5 years from when initially dosed in preceding IVORY trial
Secondary	All-cause deaths comparing IL2 to placebo	Number of all-cause deaths comparing IL2 to placebo	1 year from when initially dosed in preceding IVORY trial
Secondary	All-cause death comparing IL2 to placebo	Number of all-cause deaths comparing IL2 to placebo	2 years from when initially dosed in preceding IVORY trial
Secondary	All-cause death comparing IL2 to placebo	Number of all-cause deaths comparing IL2 to placebo	5 years from when initially dosed in preceding IVORY trial
Secondary	Hospitalisations due to symptoms from heart failure (incl admission due to pulmonary oedema and congestive heart failure) comparing IL2 to placebo	Number of hospitalisations due to symptoms from heart failure (incl admission due to pulmonary oedema and congestive heart failure) comparing IL2 to placebo	1 year from when initially dosed in preceding IVORY trial
Secondary	Hospitalisations due to symptoms from heart failure (incl admission due to pulmonary oedema and congestive heart failure) comparing IL2 to placebo	Number of hospitalisations due to symptoms from heart failure (incl admission due to pulmonary oedema and congestive heart failure)comparing IL2 to placebo	2 years from when initially dosed in preceding IVORY trial
Secondary	Hospitalisations due to symptoms from heart failure (incl admission due to pulmonary oedema and congestive heart failure) comparing IL2 to placebo	Number of hospitalisation 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
Secondary	Revascularisations for peripheral vascular disease comparing IL2 to placebo	Number of revascularisations for peripheral vascular disease comparing IL2 to placebo	1 year from when initially dosed in preceding IVORY trial
Secondary	Revascularisations for peripheral vascular disease comparing IL2 to placebo	Number of revascularisations for peripheral vascular diseasecomparing IL2 to placebo	2 years from when initially dosed in preceding IVORY trial
Secondary	Revascularisations for peripheral vascular disease comparing IL2 to placebo	Number of revascularisations for peripheral vascular disease comparing IL2 to placebo	5 years from when initially dosed in preceding IVORY trial
Secondary	Amputations due to peripheral vascular disease comparing IL2 to placebo	Number of amputations due to peripheral vascular disease comparing IL2 to placebo	1 year from when initially dosed in preceding IVORY trial
Secondary	Amputations due to peripheral vascular disease comparing IL2 to placebo	Number of amputations due to peripheral vascular disease comparing IL2 to placebo	2 years from when initially dosed in preceding IVORY trial
Secondary	Amputations due to peripheral vascular disease comparing IL2 to placebo	Number of amputations due to peripheral vascular disease comparing IL2 to placebo	5 years from when initially dosed in preceding IVORY trial
Secondary	Haemorrhagic strokes comparing IL2 to placebo	Number of haemorrhagic strokes comparing IL2 to placebo	1 year from when initially dosed in preceding IVORY trial
Secondary	Haemorrhagic strokes comparing IL2 to placebo	Number of haemorrhagic strokes comparing IL2 to placebo	2 years from when initially dosed in preceding IVORY trial
Secondary	Haemorrhagic strokes comparing IL2 to placebo	Number of haemorrhagic strokes comparing IL2 to placebo	5 years from when initially dosed in preceding IVORY trial
Secondary	New atrial fibrillation diagnosis comparing IL2 to placebo	Number of new atrial fibrillation diagnoses comparing IL2 to placebo	1 year from when initially dosed in preceding IVORY trial
Secondary	New atrial fibrillation diagnosis comparing IL2 to placebo	Number of new atrial fibrillation diagnoses comparing IL2 to placebo	2 years from when initially dosed in preceding IVORY trial
Secondary	New atrial fibrillation diagnosis comparing IL2 to placebo	Number of new atrial fibrillation diagnoses comparing IL2 to placebo	5 years from when initially dosed in preceding IVORY trial
Secondary	Ventricular arrhythmia (sustained ventricular tachycardia and ventricular fibrillation) comparing IL2 to placebo	Number of ventricular arrhythmia episodes (sustained ventricular tachycardia and ventricular fibrillation) comparing IL2 to placebo	1 year from when initially dosed in preceding IVORY trial
Secondary	Ventricular arrhythmia (sustained ventricular tachycardia and ventricular fibrillation) comparing IL2 to placebo	Number of ventricular arrhythmia episodes (sustained ventricular tachycardia and ventricular fibrillation) comparing IL2 to placebo	2 years from when initially dosed in preceding IVORY trial
Secondary	Ventricular arrhythmia (sustained ventricular tachycardia and ventricular fibrillation) comparing IL2 to placebo	Number of ventricular arrhythmia episodes (sustained ventricular tachycardia and ventricular fibrillation) comparing IL2 to placebo	5 years from when initially dosed in preceding IVORY trial