LDL-C Optimization Using Inclisiran in Patients in Which Drug-Drug Interactions Limit LDL Lowering
Study of Optimal LDL-C Value Enhancement With Inclisiran in Patients With Multiple Comorbidities in Which There Are Drug-Drug Interactions Limiting LDL-C Lowering
University of California, San Diego
100 participants
Apr 3, 2025
INTERVENTIONAL
Summary
Drug-drug interactions often limit statin optimization in a population of patients prescribed cytochrome P3A4 inhibitors, which include immunosuppressive agents, protease inhibitors, and antifungals. These patients frequently have autoimmune conditions or rheumatologic disorders that require complex drug regimens and are often on low-dose statin therapy or no statin at all, resulting in suboptimal LDL levels despite increased cardiovascular (CV) risk. There is an unmet clinical need to improve LDL levels in this vulnerable patient population, which faces increased CV risk due to underlying conditions that also contribute to polypharmacy and multiple drug-drug interactions. This study is a randomized, open-label trial evaluating subcutaneous inclisiran plus standard of care for LDL-C lowering in high-risk primary prevention patients with multiple comorbidities (e.g., Type II diabetes, liver disease, chronic kidney disease, autoimmune disease, solid-organ transplant) who are taking five or more medications in which drug-drug interactions prevent optimization of statin therapy.
Eligibility
Inclusion Criteria15
- 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 Criteria10
- 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.
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Interventions
The intervention arm will receive subcutaneous injection of inclisiran 284mg at the baseline visit, 3 months and 9 month visit.
Locations(1)
View Full Details on ClinicalTrials.gov
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NCT06865885