OptimiZation Of Lipid Lowering Therapies Using a Decision Support System In Patients With Acute Coronary Syndrome.

Myocardial Infarction Clinical Trial

— ZODIAC  

Official title:

Implementation of a Decision Support System and Its Effect on Early Optimisation of Lipid-Lowering Therapies in Patients With Acute Coronary Syndrome: a Cluster Randomised Controlled Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05844566
• Other study ID #: 22HH7982
• Status: Recruiting
• Phase: N/A
• Start date: April 3, 2023
• Est. completion date: March 31, 2024

Study information

• Verified date: December 2023
• Source: Imperial College London
• Contact: Maria Moreno Morales
• Phone: +44 (0) 7935 352902
• Email: m.moreno-morales[@]imperial.ac.uk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this clinical trial is to compare implementation of a Decision Support System (DSS) - aligned to the 2019 ESC/EAS Guidelines - in addition to routine clinical care versus routine clinical care without availability of a DSS, in participants aged ≥18 to < 80 years old presenting with Acute Coronary Syndrome (ACS).

The main questions it aims to answer are:

• to assess whether the availability of a DSS (which provides estimates of risk and estimates of potential benefit through LDL-C lowering) to current practice results in an increase in the early initiation of combination Lipid Lowering Therapies (LLTs) or intensification of LLT regimens compared to current practice alone over a 24-week period after an Acute Coronary Syndromes (ACS) event

• To estimate in the study cohort the potential benefits of guideline-based LLT intensification via simulation-based methods using estimates of baseline risk: LLT utilisation, additional LDL-C reductions and LDL-C goal achievement, on simulated risk of CV events through modelling.

Participants will give consent to randomised clinical sites to collect their data. The clinical sites will either be randomised to standard of care or the availability of and access to the DSS.

Researchers will compare patients from DSS and Non-DSS sites to see if the availability of the DSS results in implementation of more intensive lipid lowering regimens, resulting in the achievement of lower LDL-C values as well as the proportion of patients who reach target LDL-C levels (<1.4 mmol/L (<55 mg/dL) by Week 24.

Description:

Patients with acute coronary syndromes (ACS) including myocardial infarction (MI) remain at risk of future cardiovascular events depending upon the interaction between inherited genetic factors/ and environmental factors including cholesterol over their lifetime. Expert guidelines on secondary prevention such as the ESC therefore increasingly recognise a more individualised approach.

Lowering LDL-C with high intensity lipid lowering therapies (LLTs) initiated within 10 days of an ACS reduces risk more than less intense regimens. In the SWEDEHEART registry which included 40,6007 patients over a median follow up of 3.78 years, patients who achieved the largest absolute reductions in LDL-C or greatest percentage reduction in LDL-C, had the lowest risk of a range of cardiovascular events and mortality. The approach to use of lipid lowering (LLT) was statin based monotherapy with few attaining the recommended cholesterol goals.

The 2019 European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS) dyslipidaemia guidelines categorise patients with an ACS event as very-high risk and recommend an LDL-C goal of < 1.4 mmol/L (<55 mg/dL) and >50% reduction in LDL-C in this population. But several studies in European populations have highlighted gaps between clinical practice/ implementation of treatment recommendations compared with evidence based guideline recommendations. In the DA VINCI study representing 5,888 patients prescribed LLT in 18 European countries, LDL-C goal achievement in very-high risk populations was just 39% per 2016 ESC/EAS guidelines of<1.8mmol/L with only about 18% achieving the new recommended lower goal of <1.4mmol/L. It has become clear that greater implementation/ use of available combination therapies will be needed if lower recommended goals are to be achieved. It is unclear what the barriers are to earlier implementation and may include a lack of physician understanding of risk of further CV events or a lack of understanding of the quantifiable benefits from specific magnitudes of LDL-C lowering.

The aim of this trial is to assess whether providing information to those managing ACS patients that quantify absolute risk and the absolute benefit from different lipid lowering regimens through access to a Decision Support Tool (DSS) system is more likely to result in earlier intensification of lipid lowering regimens and thus result in a greater proportion of patients achieving the ESC lipid lowering goals after ACS compared to patients being managed routinely without access to a DSS standard (cluster RCT design). It is well established that unless treatments are initiated through secondary care or as part of acute care pathways, there is considerable inertia in further optimisation of treatment in primary care. Thus, this trial will assess whether presenting quantifiable data on risks and benefits results in behaviour change among secondary care physicians and improves cholesterol management within 6 months of an ACS.

The DSS is available online or remotely accessible via a website intended for clinicians to estimate the clinical benefit of any LLT regimen, whether single or combination therapies. The DSS shows the expected risk, risk reductions and number needed to treat for the various treatments selected by the clinical user on the potential value of initiation of an add-on therapy for reducing the risk of other Cardiovascular (CV) events. This DSS provides a graphical and tabular representation of the time-dependent CV treatment benefit model for LLTs published in a peer-reviewed journal article.

The trial hypothesises that having a pictorial representation of both individual risk and recommended treatments will encourage clinicians to implement clinical guidelines more closely. The clinicians using the DSS will be asked to complete a DSS evaluation at the end of the trial. Implementing the patient-specific recommendation remains at the clinicians' discretion.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1584
• Est. completion date: March 31, 2024
• Est. primary completion date: March 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 79 Years

Eligibility

Inclusion criteria:

Sites:

• Manage ACS patients as defined by: Symptoms of myocardial ischemia with an unstable pattern, occurring at rest or with minimal exertion, within 72 hours of an unscheduled hospital admission due to presumed or proven obstructive coronary disease and at least one of the following:

• Elevated cardiac biomarkers

• Resting electrocardiographic changes consistent with ischemia or infarction, plus additional evidence of obstructive coronary disease from regional wall motion or perfusion abnormality, 70% or more epicardial coronary stenosis by angiography, or need for coronary revascularization procedure

• Mange post ACS follow up care of patients including risk factor control

• Ability to provide follow up information on patient care for a minimum of 24 weeks including blood tests

• Willing/ able to access and undertake training for the DSS

• Adequate internet connection at site and the ability to access the DSS

• No restrictions on use of LLTs (within national guidelines/ reimbursement)

• Ability to include all essential parameters and patient information for DSS input

Participants:

• Aged =18 to < 80 years old

• Provide written informed consent

• Presenting to a study site with ACS as LLT naïve, monotherapy or combination therapy (defined as more than one LLT agent)

• Willing to take lipid lowering treatments for the secondary prevention of cardiovascular disease

• Attending the same study site (or same clinical team) for ACS follow up to ensure follow up data can be collected; or ensure that follow up data can be collected from other clinical institutions as part of the clinical pathway.

Exclusion criteria:

Sites:

• Unable to capture/ provide data on patients with ACS during admission and follow up

• Unable or unwilling to use lipid lowering treatments other than statins for ACS care

Participants:

• Unable to provide written informed consent

• LDL-C measurement < 1.8 mmol/L at admission

Related Conditions & MeSH terms

• Acute Coronary Syndrome
• Infarction
• Ischemic Stroke
• Myocardial Infarction
• Syndrome

Intervention

Device:
• Decision Support System (DSS)
This DSS will provide estimates of potential benefits in terms of ASCVD risk reduction (composite endpoint: combined non-fatal myocardial infarction, non-fatal ischaemic stroke and cardiovascular death) as a function of treatment duration and magnitude of LDL-C lowering. The DSS does not recommend treatments but shows the expected ASCVD risk, absolute and relative ASCDV risk reductions and number needed to treat for the various treatments selected by the clinical user on the potential value of initiation of an add-on therapy for reducing the risk of recurrent Cardiovascular (CV) events. Implementing the patient-specific recommendation remains at the clinicians' discretion.

Locations

Country	Name	City	State
United Kingdom	Royal United Hospital	Bath	Somerset
United Kingdom	Sandwell General Hospital	Birmingham	West Midlands
United Kingdom	Glan Glwyd Hospital	Bodelwyddan	Denbighshire, Wales
United Kingdom	Royal Bournemouth Hospital	Bournemouth	Dorset
United Kingdom	Conquest Hospital	Brighton	East Sussex
United Kingdom	Russell's Hall Hospital	Dudley	West Midlands
United Kingdom	Calderdale Royal Hospital	Halifax	West Yorkshire
United Kingdom	Kettering General Hospital	Kettering	Northamptonshire
United Kingdom	Hammersmith Hospital	London
United Kingdom	Luton and Dunstable University Hospital	Luton	Bedfordshire
United Kingdom	Freeman Hospital	Newcastle Upon Tyne	Tyne And Wear
United Kingdom	North Tyneside General Hospital	North Shields	Tyne And Wear
United Kingdom	Scunthorpe General Hospital	Scunthorpe	North Lincolnshire
United Kingdom	Sunderland Royal Hospital	Sunderland	Tyne And Wear
United Kingdom	Worcestershire Royal Hospital	Worcester	Worcestershire
United Kingdom	Worthing Hospital	Worthing	West Sussex

Sponsors (3)

Lead Sponsor	Collaborator
Imperial College London	Axtria, Inc., Sanofi

Country where clinical trial is conducted

United Kingdom, 

References & Publications (27)

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* Note: There are 27 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Optimisation of the intensity of Lipid Lowering Therapy within 24 weeks of index ACS	Proportion of patients treated with combination therapy, or who receive escalated monotherapy, or escalated combination therapy, within 24 weeks of the index ACS.	24 weeks
Secondary	Time to initiation	Time to initiation of combination therapy or escalation of Lipid lowering therapy as defined in the primary endpoint	24 weeks
Secondary	LDL-C Level	LDL-C by Week 24	24 weeks
Secondary	Target LDL-C reduction	Proportion of patients reaching target LDL-C level (<1.4 mmol/L (<55 mg/dL) by Week 24	24 weeks

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