V-INCLUSION

Currently Recruiting: Participants

Study Drug/Intervention: Inclisiran

Anticipated Sample Size: 1,440 patients

Study Timeline: This study is expected to recruit its first patient in September 2024 and conclude enrollment in May 2025, with final follow-up occurring by May 2027.

ClinicalTrials.gov ID: NCT06249165

What is V-INCLUSION?

V-INCLUSION is a phase IV, multicenter, randomized, open-label trial. The aim is to assess the effectiveness of inclisiran and usual care compared to usual care alone in addressing care gaps within a pragmatic framework. The study focuses on an inclusive and underrepresented population at high risk for or diagnosed with atherosclerotic cardiovascular disease (ASCVD). The participants will be those who are typically underrepresented in cardiovascular clinical trials and who face disparities in ASCVD risk identification and LDL-C management, as well as inequitable ASCVD outcomes (including women, racial and ethnic minorities, and rural participants). The study will use electronic health records (EHR) to efficiently identify individuals at high risk for or already diagnosed with ASCVD, but whose LDL-C levels remain above guideline-recommended thresholds despite receiving usual care.

Study Objective

To evaluate the impact of inclisiran and usual care versus usual care alone on LDL-C control at day 360 in underrepresented and historically understudied patient groups in the U.S.

Unique Aspects of Project

V-INCLUSION will only enroll underrepresented groups. All participants will receive inclisiran in either year one or year two.

Inclusion Criteria

1. Males and females ≥18 years of age.
2. Have clinical ASCVD or ASCVD risk equivalent diagnosis captured in EHR. 
3. Serum LDL-C ≥ 70 mg/dL for participants with ASCVD, or LDL-C ≥ 100 mg/dL for ASCVD risk equivalent participants, based on last recorded LDL-C value within the preceding eighteen (18) months without a subsequent change in lipid lowering therapy.
4. Willing and able to give informed consent and willing to comply with all required study procedures.
5. On statin therapy, or have documented statin intolerance
6. From historically underrepresented populations in cardiovascular clinical research, including:
   1. Female sex
   2. Hispanic/Latino ethnicity
   3. Black/African-American, Asian, or Native American race
   4. Rural dwelling (based on the HRSA definition for determining rural grant eligibility - view here).

Exclusion Criteria

1. Planned use of other investigational products or devices during the course of the study.
2. Treatment with monoclonal antibodies directed towards PCSK9 within 90 days or with inclisiran within 180 days of pre-screening.
3. History of hypersensitivity to the study treatment or its excipients or to other siRNA drugs.
4. Pregnant or nursing (lactating) women.
5. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using basic methods of contraception during dosing of study treatment. 
6. New York Heart Association (NYHA) class III or IV heart failure or last known left ventricular ejection fraction <25%.
7. Significant cardiac arrhythmia within 3 months prior to randomization that is not controlled by medication or other methods (i.e. via ablation etc.) at the time of pre-screening.
8. Uncontrolled hypertension: systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg prior to randomization despite antihypertensive therapy.
9. Active liver disease 
10. End-stage renal disease (ESRD)

Underrepresented and historically understudied male and female participants - at least 50% of female participants and 70% from underrepresented groups (Black/African American, Hispanic/Latino, Asian, other), as well as 10% rural participants of any sex or race/ethnicity, who meet the eligibility requirements.

Study Sites

30 U.S. sites

Duration of Study Participation

Up to two years

Study Follow-Up

Participants randomized to inclisiran and usual care have four visits over one year; participation ends after one year. Those randomized to usual care alone have seven visits over two years, receiving inclisiran in year two.

Please contact V-INCLUSION@duke.edu for more information.