ASCERTAIN: AtheroSclerotic Cardiovascular disEase Risk assessmenT and treAtment In AustraliaN Primary Care

Sponsor

Monash University (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05834673

Collaborator

Novartis Pharmaceuticals (Industry)

600

Enrollment

Location

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The goal of this observational study is to understand and compare an alternative model of care in comparison to the usual model of care in include male and female participants ≥18 years of age with a history of ASCVD (hear and blood vessels diseases) or high-risk participants who have elevated bad cholesterol (LDL-C ≥1.8 mmol/L). The alternative model of care includes telephone support calls from a study nurse (after visits 1,2 and 4) and text messages to your mobile phone with healthy heart information.

The main question it aims to answer is to understand and compare an alternative model of care in comparison to the usual model of care by evaluating the study participants bad cholesterol values after 180 and 365 days of the study.

Each participant will take their medications as per usual care but may have the addition of Inclisiran, 284 mg 1.5 ml liquid in a single-use prefilled syringe for under skin administration. In accordance with the current medical practice guidelines for treating heart related conditions, inclisiran and its product information will be made available for use in both care models.

All the participants who decide to take part in this study will be requested to do the following:

Answer any questions from the study doctor or the study staff as accurately as possible when asked about changes in health status, medications, heart health, visits to other doctors or hospital admissions, planned surgery, even if they think none of these are related to the study.
Study doctor will be able to inform them of which medications you can and cannot take as part of this study.
To use mobile phone to receive text messages and/or questionnaires as proposed in the new model of care.
Advise the study doctor if they plan to move away from the geographical area where the study is being conducted during the study period.
Take the medications for cholesterol lowering treatment (such as a statin and/or ezetimibe) that are prescribed by the study doctor.
Tell the study doctor or study staff as soon as possible about suspected participant / participant partner pregnancy.
Tell the study doctor or study staff if they change their mind about taking part in the study.
Attend all the visits (screening visit, visits 1, 2, 3, 4 and visit 5).
Provide all the information that will enable the study team to contact them, i.e., inform the study staff if contact details change, provide contact details of a family member, etc.

Condition or Disease	Intervention/Treatment	Phase
Atherosclerotic Cardiovascular Disease (ASCVD) Coronary Heart Disease (CHD) Cerebrovascular Disease Peripheral Arterial Disease (PAD)	Drug: Inclisiran Prefilled Syringe

Detailed Description

ASCVD remains a significant burden in the Australian population. Moreover, based on recent local data, it is clear that there are still opportunities to improve the management of this condition in Australia.

In collaboration with leading experts in the field, analysis of the gaps in management of cholesterol in Australia has been undertaken. Key areas identified include Lack of regular lipid testing in general practice, Limited access to full range of management tools, current therapies aren't achieving clinical guidelines and poor medication adherence.

To address these pain points, the ASCERTAIN study will implement a new model of care that has been co-created with leading cardiologists in Australia and feedback has been provided by a General Practitioner (GP) Advisory Committee.

As the primary purpose of this study is to assess the impact of a new model of care compared to usual care, inclisiran and its approved Product Information will be made available in both arms to be used as per the treating physician's discretion. Participants taking part in this study will receive maximally tolerated statin and/or ezetimibe therapy with or without other LDL-C lowering therapies as per the treating physician's discretion.

The primary clinical question of interest is:

What is the effectiveness of a new model of care implementation strategy compared to usual care in patients who have not reached their LDL-target?

In the usual care arm:

1- The GPs will be educated on the European Society of Cardiology (ESC) guidelines and Guideline Directed Management therapy (GDMT)

In the new model of care arm -

The GPs will be educated on the ESC guidelines and Guideline Directed Management therapy (GDMT).
The Participants enrolled in this arm will be receiving monthly short message service (SMS) messages with regards to regarding cardiovascular health and appointment reminders (low touch engagement nudges).
In addition, Participants will receive telephone-based support calls from a study nurse trained in motivational interviewing. These telephone calls will cover diet, exercise, medication, and where necessary smoking cessation. A summary of any recommendations will then be sent to the primary care physician via email or letter. However, ultimately the primary care physician is responsible for the management of their patient.

The study will include male and female participants ≥18 years of age with a history of ASCVD (coronary heart disease, ischaemic cerebrovascular disease or peripheral arterial disease) or ASCVD-risk equivalents who have elevated LDL-C (≥1.8 mmol/L). A total of approximately 600 participants will be included in the study and will be randomised in a 1:1 ratio at approximately 20 sites across Australia.

For the purposes of defining the ASCVD-risk equivalent group, the Guidelines for the Management of Absolute Cardiovascular Disease Risk (2012) in Australian adults will be used. As per these guidelines, the online calculator www.cvdcheck.org.au (which is based on the Framingham Risk Equation) will be used to calculate an individual's estimated 5-year absolute CVD risk. High risk corresponds to >15% probability of CVD within the next 5 years.

As this study will utilise Electronic Health Records (EHR), only clinics using Medical Director (MD) Clinical software will be able to participate in this study. Potential sites may be identified by running a search of the practice databases. From a recruitment and practicality perspective, in the first instance, those clinics that have a high volume of potential patients who meet the eligibility criteria will be considered. Additional formal feasibility assessment will be completed by the Sponsor to ensure clinics are suitable for participation in the study.

Study sites may receive a list of patients who could qualify for the study. This list will be generated by a search of the practice database running a query for patients that satisfy the inclusion criteria. Alternatively, the sites may identify patients who could qualify for the study independently. The study sites will contact participants who meet the eligibility criteria.

Patient Reported Outcomes (PROs) will be completed by the participant electronically. Participants will receive a link to the questionnaire via text message or email.

The analysis will be performed at the end of the study, after the data for all participants are available. Unless otherwise specified, all statistical tests will be conducted against a two-sided alternative hypothesis, employing a significance level of 0.05.

Efficacy, safety, and other data will be summarised. For continuous variables, summary statistics (mean, standard deviation, median, interquartile range, minimum, and maximum) at each time point and for change from baseline to each time point will be reported by study arm. For discrete variables, frequency counts and percentages at each time point will be reported by study arm.

Study Design

Study Type:

Observational

Anticipated Enrollment :

600 participants

Observational Model:

Other

Time Perspective:

Prospective

Official Title:

A 2-arm Multicentre Phase IV, Randomised, Open-label Study to Evaluate the Implementation and Utility of a Primary Care Model in Patients With Atherosclerotic Cardiovascular Disease (ASCVD) or ASCVD-risk Equivalents and Elevated LDL-C

Anticipated Study Start Date :

Jun 1, 2023

Anticipated Primary Completion Date :

Dec 1, 2024

Anticipated Study Completion Date :

Jun 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Usual Care Model Usual care arm : The GPs will be educated on the ESC guidelines and Guideline Directed Management therapy (GDMT) Inclisiran is available for this arm	Drug: Inclisiran Prefilled Syringe Inclisiran, 284 mg, 1.5 ml Liquid in a single-use prefilled syringe (PFS) for s.c. administration and any standard medications to be used within registered indication and at the treating physician's discretion. Other Names: LEQVIO
New Model of Care Model of care arm The GPs will be educated on the ESC guidelines and Guideline Directed Management therapy (GDMT) The Participants enrolled via these sites arm will be getting receive monthly SMS messages with regards to regarding cardiovascular health and appointment reminders (low touch engagement nudges) In addition, Participants will receive telephone-based support calls from a study nurse trained in motivational interviewing. These telephone calls will cover diet, exercise, medication, and where necessary smoking cessation. A summary of any recommendations will then be sent to the primary care physician via email or letter. Inclisiran is available for this arm.	Drug: Inclisiran Prefilled Syringe Inclisiran, 284 mg, 1.5 ml Liquid in a single-use prefilled syringe (PFS) for s.c. administration and any standard medications to be used within registered indication and at the treating physician's discretion. Other Names: LEQVIO

Arm

Intervention/Treatment

Usual Care Model

Usual care arm : The GPs will be educated on the ESC guidelines and Guideline Directed Management therapy (GDMT) Inclisiran is available for this arm

Drug: Inclisiran Prefilled Syringe

Inclisiran, 284 mg, 1.5 ml Liquid in a single-use prefilled syringe (PFS) for s.c. administration and any standard medications to be used within registered indication and at the treating physician's discretion.

Other Names:

LEQVIO

New Model of Care

Model of care arm The GPs will be educated on the ESC guidelines and Guideline Directed Management therapy (GDMT) The Participants enrolled via these sites arm will be getting receive monthly SMS messages with regards to regarding cardiovascular health and appointment reminders (low touch engagement nudges) In addition, Participants will receive telephone-based support calls from a study nurse trained in motivational interviewing. These telephone calls will cover diet, exercise, medication, and where necessary smoking cessation. A summary of any recommendations will then be sent to the primary care physician via email or letter. Inclisiran is available for this arm.

Drug: Inclisiran Prefilled Syringe

Other Names:

LEQVIO

Outcome Measures

Primary Outcome Measures

Effect on LDL-C [Baseline and 180 Days]
LDL-C at baseline and at day 180

Secondary Outcome Measures

Effect on LDL-C [365 Days]
LDL-C at baseline and at day 365

Other Outcome Measures

Patient satisfaction [Baseline,180 and 365 Days]
CSQ-8 (client satisfaction questionnaire) score at baseline, and days 180 and 365
Patient activation [Baseline,180 and 365 Days]
Patient activation measure (PAM) questionnaire score at baseline, and days 180 and 365
LDL-C control [90 and 270 Days]
LDL-C to target (Primary prevention <2.0 mmol/L, Secondary prevention <1.8mmol/L, and secondary prevention for patients at very high risk <1.4mmol/L)
Blood Pressure - Control over Risk factors [90 and 270 Days]
Blood pressure <130mmHg
HbA1c - Control over Risk factors [90 and 270 Days]
HbA1c <7%
BMI- Control over Risk factors [90 and 270 Days]
BMI <25kg/m2 (BMI is calculated by dividing the weight in Kilograms by the height in meters)
Smoking Status- Control over Risk factors [90 and 270 Days]
Non-smoking status
Medication adherence [365 Days]
Proportion of patients reporting high levels of adherence to lipid lowering therapy between both arms.
Lowering absolute cardiovascular (CV) risk [180 Days]
Absolute risk at day 180 as assessed by the CVD Check Calculator: www.cvdcheck.org.au/calculator).
Health care resourcing consumption [180 and 365 Days]
The health care resourcing consumption of each of the models of care as assessed by Medicare item number utilisation if feasible.
scalability of the model of care for a broader population-1 [180 and 365 Days]
Study sites characteristics / patients' demographics relationship to Intensification of LDL-C lowering therapy as per GDMT
scalability of the model of care for a broader population-2 [180 and 365 Days]
Study sites characteristics / patients' demographics relationship to effectiveness of CV risk factor lowering.
Lp(a) levels [180 Days]
Lp(a) levels at baseline and day 180
Changes in Lp(a) levels [180 Days]
The percentage change in Lp(a) from baseline to Day 180

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Signed informed consent must be obtained prior to participation in the study
Males and females ≥18 years of age
Documented History of ASCVD

Coronary heart disease (CHD):

Prior myocardial infarction
Prior coronary revascularisation (PCI or CABG)

Cerebrovascular disease:

Prior documented ischaemic stroke
Documented Carotid artery stenosis >70%
History of prior percutaneous or surgical carotid artery revascularisation.

Peripheral arterial disease (PAD):

History of prior percutaneous or surgical revascularisation of an iliac, femoral, or popliteal artery or aortic aneurysm in electronic patient history
Prior surgical amputation of a lower extremity due to peripheral artery disease.

OR ASCVD risk equivalents as per assessed by the online tool (>15% probability of CVD event within the next 5 years www.cvdcheck.org.au/calculator) or at clinically determined high risk.

Serum LDL-C above target ≥1.8 mmol/L (≥70 mg/dL) for ASCVD patients or ≥2.0 mmol/L for ASCVD risk equivalent patients
Not at Guideline directed cholesterol goals
On a stable dose of lipid-lowering therapy (such as a statin and/or ezetimibe) for ≥30 days before screening with no planned medication or dose change. Statin intolerant patients are eligible if intolerance is documented.

Exclusion Criteria:

Any medical or surgical history and or condition that might limit the individual's ability to take part in the study and/or put the participant at significant risk (according to physician's judgment).
Any underlying known disease, or surgical, physical, or medical condition that, in the opinion of the physician might interfere with the interpretation of the study results, including pregnancy.
Previous, current, or planned treatment with a monoclonal antibody targeting PCSK9.
Participants unable to access or unwilling to use mobile phone to receive text messages and/or questionnaires as proposed in the new model of care.
Participants who plan to move away from the geographical area where the study is being conducted during the study period.