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
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.
Description
This is an investigator-initiated, single-site, open-label, randomized trial. The investigators will enroll up to 100 high-risk primary prevention patients with at least one comorbidity and an indication for additional lipid control (such as Type II diabetes with A1c ≤ 8.5%, subclinical atherosclerosis, or ASCVD risk of 7.5% or greater). Patients will be randomized 1:1 to the inclisiran arm (n ≥ 50) with standard of care or standard of care alone (n ≥ 50). The study will consist of five study visits (screening, baseline, 3 months, 9 months, and 12 months). Patients in the inclisiran arm will…
Eligibility
- Age range
- 18–85 years
- Sex
- All
- Healthy volunteers
- No
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 vasc…
Interventions
- DrugInclisiran sodium 300 mg (equivalent to 284 mg inclisiran) in 1.5 mL
The intervention arm will receive subcutaneous injection of inclisiran 284mg at the baseline visit, 3 months and 9 month visit.
Location
- UC San Diego Altman Clinical and Translational Research InstituteLa Jolla, California