A Non-interventional Implementation Study to Evaluate Treatment With Inclisiran (Leqvio®) and Other Lipid Lowering Treatments in a Real-world Setting

Study Overview
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Brief Summary
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This is a multicenter, non-randomized, non-interventional three-cohort study with prospective collection of primary data of treatment with newly initiated oral Lipid lowering treatment on top of a statin (Oral LLT cohort), newly initiated Inclisiran (Inclisiran cohort) and newly initiated Inclisiran on top of lipid apheresis (Apheresis plus Inclisiran cohort) in routine clinical care. All procedures, treatment adaptions and laboratory assessments are part of clinicla routine and conducted independent of this study.

Official Title
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A Non-interventional Implementation Study to Evaluate Treatment With Inclisiran (Leqvio®) and Other Lipid Lowering Treatments in a Real-world Setting (VICTORION-Implement)

Conditions
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Hypercholesterolemia

Intervention / Treatment
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* Other: Inclisiran


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who provide written informed consent to participate in the study Male or female patients ≥ 18 years of age Oral LLT Cohort: Patients with documented ASCVD newly initiated on an oral lipid lowering treatment on top of a statin (e.g. ezetimibe, bempedoic acid, cholestyraimin) Inclisiran Cohort: Patients newly initiated on Inclisiran fulfilling the restricted reimbursement criteria or individual access requirements who are not at LDL-C goal as per their CV risk as recommended in the 2019 EAS/ESC guidelines (Mach et al., 2020). At least 60% of the documented patients must be PCSK9-inhibitor naive Apheresis plus Inclisiran Cohort: Patients with Inclisiran on top of regular weekly or bi-weekly lipoprotein apheresis (LDL-c or LP(a)). Exclusion Criteria: Oral LLT Cohort: Patients who receive a PCSK9-mAB or other PCSK9-targeted therapy Inclisiran 1 Cohort: current or previous PCSK9-targeted treatment Contraindication for Inclisiran according to the SmPC Patients who have received Inclisiran previously Patients with homozygous FH Any underlying known disease, or surgical, physical, or medical condition that, in the opinion of the investigator (or delegate) might interfere with interpretation of the clinical study results. Simultaneous or planned participation in an interventional research study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Oral LLT<br>Patients who newly initiated oral Lipid lowering treatment (LLT) on top of a statin | |
| Inclisiran<br>Patients who newly initiated Inclisiran Inclisiran in a PCSK9-treatment naive cohort Inclisiran in patients with prior PCSK9-antibody treatment | Other: Inclisiran<br>* Prospective observational cohort study. There is no treatment allocation. Patients administered Inclisiran by prescription will be enrolled.<br>|
| Apheresis plus Inclisiran<br>Patients who newly initiated Inclisiran on top of lipid apheresis | Other: Inclisiran<br>* Prospective observational cohort study. There is no treatment allocation. Patients administered Inclisiran by prescription will be enrolled.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Date of first Atherosclerotic Cardiovascular Disease (ASCVD) diagnosis | Date of first Atherosclerotic Cardiovascular Disease (ASCVD) diagnosis is collected | Baseline | 
| Number of patients with cardiovascular events | Number of patients with cardiovascular events is collected | Baseline | 
| Number of participants with concomitant medication in the previous 12 months | Number of participants with concomitant medication in the previous 12 months is collected | Baseline | 
| Number of apheresis treatments in the previous 12 months | Number of apheresis treatments in the previous 12 months is collected | Baseline | 
| Lipid lowering therapy used in the previous 12 months | Lipid lowering therapy used in the previous 12 months is collected | Baseline | 
| Apheresis plus Inclisiran Cohort: Number of lipid apheresis conducted | Number of lipid apheresis conducted on Apheresis plus Inclisiran cohort is collected | Baseline | 
| Low Density Lipoprotein cholesterol (LDL-C) | Low Density Lipoprotein cholesterol (LDL-C) is collected | Baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of In- and outpatient visits | Number of In- and outpatient visits is collected | 21 months | 
| Number of examinations | Number of examinations is collected | 21 months | 
| Number and types of lipid lowering treatments | Number and types of lipid lowering treatments are collected | 21 months | 
| Number of consultations | Number of consultations beside regular visits are collected | 21 months | 
| Inclisiran Cohort: Percentage of patients progressing to lipoprotein apheresis after initial Inclisiran therapy over time | Percentage of patients progressing to lipoprotein apheresis after initial Inclisiran therapy over time is collected for the Inclisiran Cohort. | 21 months | 
| Percentage of days covered by at least one LLT | Percentage of days covered (PDC) by at least one lipid lowering treatment (LLT) is collected | 21 months | 
| Percentage of patients with a PDC ≥ 80% months | Percentage of patients with a Percentage of days covered (PDC) ≥ 80% months is collected | 21 months | 
| Time to discontinuation of Inclisiran/ any LLT | Time to discontinuation of Inclisiran/ any lipid lowering treatment (LLT) is collected | 21 months | 
| Percentage of patients who discontinue Inclisiran/ any LLT | Percentage of patients who discontinue Inclisiran/ any lipid lowering treatment (LLT) is collected | 21 months | 
| Change in LDL-C compared to baseline | Change in Low denisty lipoprotein cholesterine (LDL-C) compared to baseline is measured | Baseline, month 3, month 9, month 15, month 21 | 
| Changes in TC, HDL-C and non-HDL-C compared to Baseline | Changes in total cholesterol (TC), High Denisty lipoprotein C (HDL-C) and non-HDL-C compared to Baseline is measured | Baseline, month 3, month 9, month 15, month 21 | 
| Change in c-reactive protein compared to baseline | Change in c-reactive protein compared to baseline is measured | Baseline, month 3, month 9, month 15, month 21 | 
| Changes in triglycerides and LP(a) compared to baseline | Changes in triglycerides and Lipoprotein (a) (LP(a)) compared to baseline are measured | Baseline, month 3, month 9, month 15, month 21 | 
| Change in hsCRP compared to Baseline | Change in high-sensitivity C-reactive protein (hs-CRP) compared to Baseline is measured | Baseline, month 3, month 9, month 15, month 21 | 
| Change in Creatinin compared to baseline | Change in Creatinin compared to baseline is measured | Baseline, month 3, month 9, month 15, month 21 | 
| Change in HbA1c compared to baseline | Change in Glycated hemoglobin (HbA1c) compared to baseline is measured | Baseline, month 3, month 9, month 15, month 21 | 
| Change in eGFR compared to baseline | Change in Estimated Glomerular Filtration Rate (eGFR) compared to baseline is measured | Baseline, month 3, month 9, month 15, month 21 | 
| Proportion of patients achieving prespecified LDL-C targets | Proportion of patients achieving prespecified LDL-C targets based on 2019 ESC/EAS guideline for the management of dyslipidemia is collected | Baseline, month 3, month 9, month 15, month 21 | 
| Percentage of patients achieving ≥50% LDL-C reduction over time | Percentage of patients achieving ≥50% LDL-C reduction over time is collected | Baseline, month 3, month 9, month 15, month 21 | 
| Changes in SMART-Risk Scores over time compared to baseline | The SMART Risk Score is a tool to estimate 10-year risk for recurrent vascular events in patients with manifest cardiovascular disease. SMART Risk Score ranges from 0 - 100 %, where higher values indicate higher cv risk. | Baseline, month 3, month 9, month 15, month 21 | 
| Proportion of patients with treatment modifications | Proportion of patients with the following treatment modifications, is collected: dose changes switching of lipid lowering treatment initiation of lipid apheresis for LDL-C | 21 months | 
| Changes from baseline in WHO Quality of Life BREF (WHOQOL-BRED)questionnaire over time | Each individual item of the WHOQOL-BREF is scored from 1 to 5 on a response scale, which is stipulated as a five-point ordinal scale. The scores are then transformed linearly to a 0-100-scale. Higher numbers indicate better QoL. | Baseline, month 3, month 9, month 15, month 21 | 
| Changes from baseline in TSQM-9 over time | Treatment Satisfaction Questionnaire for Medication-9 items (TSQM-9) domain scores range from 0 -100, with higher scores representing higher satisfaction on that domain. | Baseline, month 3, month 9, month 15, month 21 | 
| Evaluate nutritional factors via questionnaire | Questionnaire from the German Nationale Verzehrstudie II -Was esse ich is used. No score is used for the interpretation. Questions about nutrition and activities are interpreted separately and compared over time. | Baseline, month 3, month 9, month 15, month 21 | 
| Percentage of Adverse Events and Serious Adverse Events | Percentage of Adverse Events (AEs) and Serious Adverse Events (SAEs) is collected | 21 months | 
| Percentage of Adverse Events and Serious Adverse Events leading to discontinuation of therapy | Percentage of Adverse Events and Serious Adverse Events leading to discontinuation of therapy is collected | 21 months | 
| Apheresis plus Inclisiran Cohort: Changes in the rate of lipid apheresis | Changes in the rate of lipid apheresis over time after Inclisiran initiation compared to the period 12 months pre-Baseline is collected. | 12 months pre-Baseline, Baseline, month 3, month 9, month 15, month 21 | 
| Apheresis plus Inclisiran Cohort: Changes in CRP compared to baseline | Changes in high-sensitive C-reactive protein (hsCRP) are measured in labs. Values are interpresetd as; - less or 1.0 mg/l is normal 1.01 - 3.00 slightly high more than 3.0 mg/l is significantly elevated | Baseline, month 3, month 9, month 15, month 21 | 
| Apheresis plus Inclisiran Cohort: Changes in PTH | Apheresis plus Inclisiran Cohort: Changes in Parathyroid hormone (PTH) | Baseline, month 3, month 9, month 15, month 21 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypercholesterolemia, Inclisiran, Atherosclerotic Cardiovascular Disease, ASCVD