LDL-C Optimization Using Inclisiran in Patients in Which Drug-Drug Interactions Limit LDL Lowering

Launched by UNIVERSITY OF CALIFORNIA, SAN DIEGO · Mar 4, 2025

Keywords

ClinConnect Summary

This clinical trial is studying a medication called inclisiran to help lower LDL cholesterol (often referred to as "bad" cholesterol) in patients who can't use standard cholesterol-lowering drugs called statins due to interactions with other medications they are taking. Many of these patients have complex health conditions, such as autoimmune diseases or diabetes, and are on multiple medications, which can make it challenging to effectively lower their cholesterol levels. The trial aims to see if giving inclisiran as an injection, along with standard care, can improve cholesterol levels in these high-risk patients.

To participate in this study, individuals need to be between 18 and 85 years old, currently taking five or more prescription medications, and have high cholesterol levels despite being on the highest dose of statin they can tolerate. Participants will be randomly assigned to receive inclisiran injections or standard treatment and will need to commit to following the study guidelines for the duration of the trial. This study is currently recruiting participants, and those who join will help researchers understand how to better manage cholesterol levels in patients facing these unique challenges.

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Eligibility criteria

• Inclusion Criteria:
• • Provision of signed and dated informed consent form.
• • Stated willingness to comply with all study procedures and availability for the duration of the study, including potential randomization to injections.
• • Age \>18 and \<85 years and able to provide self-consent.
• • Taking five or more prescription drugs at the time of enrollment, of any type.
• * Meets at least one of the following criteria:
• • Elevated 10-year ASCVD risk score ≥7.5% (based on the ACC/AHA ASCVD Risk Estimator Plus tool).
• * Evidence of subclinical atherosclerosis including:
• • Calcification in any vascular bed, including coronary arteries and aorta. Calcification of cardiac valves. Breast calcification. Carotid plaque that is not hemodynamically significant.
• • o Type II diabetes on a stable medical regimen with HbA1c \<8.5%. Per American Diabetes Association guidelines, patients with Type II diabetes aged 40-75 years should be on a moderate-intensity statin.
• • Patients with documented partial or complete statin intolerance are eligible for enrollment.
• * On maximally tolerated statin therapy (which can be no statin for patients with documented intolerance) and have suboptimal LDL levels:
• • For patients with Type II diabetes: LDL \>70 mg/dL or non-HDL \>120 mg/dL.
• • For other patients: LDL \>90 mg/dL or non-HDL \>120 mg/dL.
• • Willing to adhere to the randomized study regimen, including subcutaneous injection of inclisiran.
• • Agreement to adhere to lifestyle considerations (see Section 5.3) throughout the study duration.
• Exclusion Criteria:
• • Prior or current use of inclisiran.
• • Known hypersensitivity or allergy to inclisiran or its components.
• • Active liver disease or unexplained persistent elevations in liver enzymes (ALT or AST \>3x upper limit of normal).
• • History of rhabdomyolysis or severe muscle-related statin intolerance.
• • Uncontrolled diabetes (HbA1c \>8.5%).
• • Active malignancy requiring systemic therapy.
• • Recent major cardiovascular event (myocardial infarction, stroke, or hospitalization for unstable angina) within the past 3 months.
• • History of organ transplant other than solid-organ transplant.
• • Pregnancy or breastfeeding.
• • Any condition that, in the opinion of the investigator, would make participation unsafe or interfere with study procedures.