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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

Recruiting
Conditions
Hypercholesterolemia
Interventions
Other: Inclisiran
Registration Number
NCT05362903
Lead Sponsor
Novartis Pharmaceuticals
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
2030
Inclusion Criteria
  1. Patients who provide written informed consent to participate in the study
  2. Male or female patients ≥ 18 years of age
  3. 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)
  4. 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
  5. Apheresis plus Inclisiran Cohort: Patients with Inclisiran on top of regular weekly or bi-weekly lipoprotein apheresis (LDL-c or LP(a)).
Exclusion Criteria
  1. Oral LLT Cohort: Patients who receive a PCSK9-mAB or other PCSK9-targeted therapy
  2. Inclisiran 1 Cohort: current or previous PCSK9-targeted treatment
  3. Contraindication for Inclisiran according to the SmPC
  4. Patients who have received Inclisiran previously
  5. Patients with homozygous FH
  6. 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.
  7. Simultaneous or planned participation in an interventional research study

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
InclisiranInclisiranPatients who newly initiated Inclisiran 1. Inclisiran in a PCSK9-treatment naive cohort 2. Inclisiran in patients with prior PCSK9-antibody treatment
Apheresis plus InclisiranInclisiranPatients who newly initiated Inclisiran on top of lipid apheresis
Primary Outcome Measures
NameTimeMethod
Apheresis plus Inclisiran Cohort: Number of lipid apheresis conductedBaseline

Number of lipid apheresis conducted on Apheresis plus Inclisiran cohort is collected

Date of first Atherosclerotic Cardiovascular Disease (ASCVD) diagnosisBaseline

Date of first Atherosclerotic Cardiovascular Disease (ASCVD) diagnosis is collected

Number of patients with cardiovascular eventsBaseline

Number of patients with cardiovascular events is collected

Number of apheresis treatments in the previous 12 monthsBaseline

Number of apheresis treatments in the previous 12 months is collected

Number of participants with concomitant medication in the previous 12 monthsBaseline

Number of participants with concomitant medication in the previous 12 months is collected

Lipid lowering therapy used in the previous 12 monthsBaseline

Lipid lowering therapy used in the previous 12 months is collected

Low Density Lipoprotein cholesterol (LDL-C)Baseline

Low Density Lipoprotein cholesterol (LDL-C) is collected

Secondary Outcome Measures
NameTimeMethod
Number of examinations21 months

Number of examinations is collected

Number and types of lipid lowering treatments21 months

Number and types of lipid lowering treatments are collected

Percentage of days covered by at least one LLT21 months

Percentage of days covered (PDC) by at least one lipid lowering treatment (LLT) is collected

Percentage of patients who discontinue Inclisiran/ any LLT21 months

Percentage of patients who discontinue Inclisiran/ any lipid lowering treatment (LLT) is collected

Changes in SMART-Risk Scores over time compared to baselineBaseline, month 3, month 9, month 15, month 21

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.

Number of consultations21 months

Number of consultations beside regular visits are collected

Inclisiran Cohort: Percentage of patients progressing to lipoprotein apheresis after initial Inclisiran therapy over time21 months

Percentage of patients progressing to lipoprotein apheresis after initial Inclisiran therapy over time is collected for the Inclisiran Cohort.

Changes in triglycerides and LP(a) compared to baselineBaseline, month 3, month 9, month 15, month 21

Changes in triglycerides and Lipoprotein (a) (LP(a)) compared to baseline are measured

Change in HbA1c compared to baselineBaseline, month 3, month 9, month 15, month 21

Change in Glycated hemoglobin (HbA1c) compared to baseline is measured

Apheresis plus Inclisiran Cohort: Changes in the rate of lipid apheresis12 months pre-Baseline, Baseline, month 3, month 9, month 15, month 21

Changes in the rate of lipid apheresis over time after Inclisiran initiation compared to the period 12 months pre-Baseline is collected.

Number of In- and outpatient visits21 months

Number of In- and outpatient visits is collected

Percentage of patients with a PDC ≥ 80% months21 months

Percentage of patients with a Percentage of days covered (PDC) ≥ 80% months is collected

Changes in TC, HDL-C and non-HDL-C compared to BaselineBaseline, month 3, month 9, month 15, month 21

Changes in total cholesterol (TC), High Denisty lipoprotein C (HDL-C) and non-HDL-C compared to Baseline is measured

Change in Creatinin compared to baselineBaseline, month 3, month 9, month 15, month 21

Change in Creatinin compared to baseline is measured

Percentage of patients achieving ≥50% LDL-C reduction over timeBaseline, month 3, month 9, month 15, month 21

Percentage of patients achieving ≥50% LDL-C reduction over time is collected

Evaluate nutritional factors via questionnaireBaseline, month 3, month 9, month 15, month 21

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.

Percentage of Adverse Events and Serious Adverse Events leading to discontinuation of therapy21 months

Percentage of Adverse Events and Serious Adverse Events leading to discontinuation of therapy is collected

Apheresis plus Inclisiran Cohort: Changes in CRP compared to baselineBaseline, month 3, month 9, month 15, month 21

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

Change in LDL-C compared to baselineBaseline, month 3, month 9, month 15, month 21

Change in Low denisty lipoprotein cholesterine (LDL-C) compared to baseline is measured

Change in c-reactive protein compared to baselineBaseline, month 3, month 9, month 15, month 21

Change in c-reactive protein compared to baseline is measured

Proportion of patients achieving prespecified LDL-C targetsBaseline, month 3, month 9, month 15, month 21

Proportion of patients achieving prespecified LDL-C targets based on 2019 ESC/EAS guideline for the management of dyslipidemia is collected

Proportion of patients with treatment modifications21 months

Proportion of patients with the following treatment modifications, is collected:

* dose changes

* switching of lipid lowering treatment

* initiation of lipid apheresis for LDL-C

Changes from baseline in WHO Quality of Life BREF (WHOQOL-BRED)questionnaire over timeBaseline, month 3, month 9, month 15, month 21

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.

Changes from baseline in TSQM-9 over timeBaseline, month 3, month 9, month 15, month 21

Treatment Satisfaction Questionnaire for Medication-9 items (TSQM-9) domain scores range from 0 -100, with higher scores representing higher satisfaction on that domain.

Apheresis plus Inclisiran Cohort: Changes in PTHBaseline, month 3, month 9, month 15, month 21

Apheresis plus Inclisiran Cohort: Changes in Parathyroid hormone (PTH)

Time to discontinuation of Inclisiran/ any LLT21 months

Time to discontinuation of Inclisiran/ any lipid lowering treatment (LLT) is collected

Change in hsCRP compared to BaselineBaseline, month 3, month 9, month 15, month 21

Change in high-sensitivity C-reactive protein (hs-CRP) compared to Baseline is measured

Change in eGFR compared to baselineBaseline, month 3, month 9, month 15, month 21

Change in Estimated Glomerular Filtration Rate (eGFR) compared to baseline is measured

Percentage of Adverse Events and Serious Adverse Events21 months

Percentage of Adverse Events (AEs) and Serious Adverse Events (SAEs) is collected

Trial Locations

Locations (1)

Novartis Investigative Site

🇩🇪

Zwiesel, Germany

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