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

What this study involves

The registry says this study is recruiting. Individual locations may have different availability.

Study type

Interventional

Phase

Phase 4

Age range

18 years - 85 years

Sex eligible

All sexes

Healthy volunteers

Not accepted

Participants

100 Estimated

These are starting points, not an eligibility decision. The research team must review the full requirements.

About the research

Polypharmacy and drug-drug interactions often limit statin optimization, including in a population of patients prescribed cytochrome P3A4 inhibitors such as, 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, etc.) who are taking five or more medications in which drug-drug interactions may prevent optimization of statin therapy.

Who may be able to participate?

The list below is the sponsor’s full registry wording. It can include conditions, prior treatment, test results and other requirements. A match in search does not mean you qualify.

Inclusion Criteria:

To be eligible to participate in this study, individuals must meet all of the following criteria:

1. Provide signed and dated informed consent form.
2. Are willing to comply with all study procedures and availability for the duration of the study including the potential randomization to injections, as stated by the participant and assessed by study staff.
3. Are ≥ 18 and ≤ 85 years of age with the ability to consent for themselves.
4. Take 5 or more medications at the time of enrollment (any type of medication). This includes prescription drugs, as well as over-the-counter drugs or supplements recommended by a healthcare provider, in line with the WHO definition of polypharmacy.
5. Meet at least one of criteria a, b, or c:

1. Elevated 10-year ASCVD risk score ≥7.5% based on the ACC/AHA Pooled Cohort ASCVD Risk Estimator Plus tool OR PREVENT-ASCVD 10-Year Risk Estimate ≥ 10% (https://tools.acc.org/ASCVD-Risk-Estimator-Plus/#!/calculate/estimate/) Or
2. Evidence of subclinical atherosclerosis:

* calcification in any vascular bed, including coronary arteries, aorta
* calcification of cardiac valves
* breast calcification
* carotid plaque that is not hemodynamically significant Or
3. Type II diabetes with HbA1c less than 8.5.
6. Take maximally tolerated dose of statin therapy (for patients that have documented statin intolerance or contraindication, this can be no statin) and have suboptimal LDL levels (LDL ≥ 70 mg/dL or non-HDL ≥ 100 mg/dL based on current treatment guidelines).
7. Are on stable lipid-lowering therapy for at least 4 weeks prior to screening. Patients can also take other non-PCSK9i lipid-lowering therapies, such as ezetimibe, bempedoic acid, icosapent ethyl, and fibrates.
8. May have potential drug-drug interactions that may limit statin dose or up-titration.
9. Agree to adhere to lifestyle considerations (see Section 5.3) throughout study duration.

Exclusion Criteria:

Individuals who meet any of the following criteria will be excluded from participation in this study:

1. Have a history of ASCVD, defined as history of myocardial infarction, atherosclerotic ischemic stroke, transient ischemic attack (TIA) of atherosclerotic ischemic origin, coronary artery bypass graft (CABG), coronary/carotid/peripheral artery/aortic stent for atherosclerotic disease, or peripheral artery disease diagnosed via imaging or ankle-brachial index).

* For heart transplant recipients, history of myocardial infarction, CABG, or coronary artery stenting is only exclusionary after most recent heart transplant.
* Non-atherosclerotic ischemic strokes or TIAs identified as cardioembolic or attributed to hypercoagulability or non-atherosclerotic vasculopathy are NOT exclusionary.
2. Are pregnant, nursing, or trying to conceive.
3. Are currently taking PCSK9 inhibitors (evolocumab, alirocumab) or are already on inclisiran. If any prior exposure to evolocumab or alirocumab, the last dose should have been at least 12 weeks prior to study enrollment. If any prior exposure to inclisiran, the last dose should have been at least 6 months prior to study enrollment.
4. Have a coronary artery calcium score ≥ 300 as these patients are considered secondary prevention patients.
5. Are currently enrolled in medical research judged not to be scientifically or medically compatible with this study as determined at the discretion of the PI.
6. Have any other medical condition(s) or take any treatment(s) deemed by the investigator to pose a risk to patient safety or interfere with study evaluation, procedures, or completion.

Treatment, groups and participation

The registry may describe treatments and study duration without a complete visit calendar. Ask the study team for the exact schedule, procedures, risks, costs and alternatives. Keep your usual care plan unless your treating clinician tells you otherwise.

Assignment

Random assignment

Masking

No masking

What researchers are measuring

Outcome measures describe what is being studied. They are not proof that a treatment works.

Primary measures

Secondary measures

Other measures

Research locations (1)

The overall study status and a local site’s status can differ. Confirm that location’s availability before traveling.

1 locations

Study team and timeline

Lead sponsor

University of California, San Diego

Study start

Apr 2, 2025 Actual

Primary completion

Jun 1, 2028 Estimated

Study completion

Sep 1, 2028 Estimated

First posted

Mar 10, 2025 Actual

Last updated

Nov 10, 2026 Actual

Official study contacts