A Randomized, Multicenter, Open-label Trial Comparing the Effectiveness of an "Inclisiran First" Implementation Strategy to Usual Care on LDL Cholesterol (LDL-C) in Patients With Atherosclerotic Cardiovascular Disease and Elevated LDL-C (≥70 mg/dL) Despite Receiving Maximally Tolerated Statin Therapy (VICTORION-INITIATE)
Overview
- Phase
- Phase 3
- Intervention
- Inclisiran
- Conditions
- Atherosclerotic Cardiovascular Disease
- Sponsor
- Novartis Pharmaceuticals
- Enrollment
- 450
- Locations
- 43
- Primary Endpoint
- Percent Change From Baseline in LDL-C
- Status
- Completed
- Last Updated
- 11 months ago
Overview
Brief Summary
The purpose of this study is to assess the effectiveness of an "inclisiran first" implementation strategy (addition of inclisiran to maximally tolerated statin therapy immediately upon failure to achieve acceptable LDL-C with maximally tolerated statin therapy alone) compared to usual care in an ASCVD population.
Detailed Description
The study design will be a randomized, two-arm, parallel-group, open-label, multicenter, clinical trial comparing an "inclisiran first" implementation strategy to usual care in approximately 444 participants (1:1 randomization) with established ASCVD and elevated LDL-C (or non-HDL-C) despite treatment with maximally tolerated statin therapy. The study will include male and female participants ≥18 years of age with a history of ASCVD (coronary heart disease, ischemic cerebrovascular disease or peripheral arterial disease) who have elevated LDL-C (≥70 mg/dL) or non-HDL-C (≥100 mg/dL) despite being treated with maximally tolerated statin therapy. A total of approximately 444 participants will be randomized to the "inclisiran first" implementation strategy or usual care in a 1:1 ratio at approximately 50 US sites.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- •Participants meeting any of the following criteria are not eligible for inclusion in this study.
- •Any uncontrolled or serious disease, or any medical or surgical condition, that may either interfere with participation in the clinical study, and/or put the participant at significant risk (according to investigator's \[or delegate\] judgment) if he/she participates in the clinical study
- •An underlying known disease, or surgical, physical, or medical condition that, in the opinion of the investigator (or delegate) might interfere with interpretation of the clinical study results
- •New York Heart Association (NYHA) class III or IV heart failure or last known left ventricular ejection fraction \<30%
- •Significant cardiac arrhythmia within 3 months prior to randomization that is not controlled by medication or via ablation at the time of screening
- •Major adverse cardiovascular event within 6 months prior to randomization
- •Uncontrolled severe hypertension: systolic blood pressure \>180 mmHg or diastolic blood pressure \>110 mmHg prior to randomization despite antihypertensive therapy
- •Severe concomitant non-cardiovascular disease that carries the risk of reducing life expectancy to less than 2 years
- •History of malignancy that required surgery (excluding local and wide-local excision), radiation therapy and/or systemic therapy during the two years prior to randomization
- •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 investigational drug. Basic contraception methods include:
Arms & Interventions
Inclisiran First
Inclisiran sodium 300 mg 1.5 ml (equivalent to 284 mg of inclisiran) + usual care
Intervention: Inclisiran
Outcomes
Primary Outcomes
Percent Change From Baseline in LDL-C
Time Frame: Baseline, Day 330
Percent change from baseline in Low-Density Lipoprotein Cholesterol (LDL-C) of an "inclisiran first" implementation strategy compared to usual care at Day 330.
Percentage of Participants Who Discontinued Statin Therapy
Time Frame: Day 330
Percentage of patients who discontinued statin therapy ≥ 30 days before the end-of-study visit of an "inclisiran first" implementation strategy compared to usual care, for patients in the FAS excluding those with a medical history of statin intolerance.
Secondary Outcomes
- Absolute Change From Baseline in LDL-C(Baseline, Day 330)
- Average Percent Change From Baseline in LDL-C Levels Across Visits(Up to 330 Days)
- Average Absolute Change From Baseline in LDL-C Levels Across Visits(Up to 330 days)
- Percentage of Participants Achieving ≥ 50% Reduction From Baseline in LDL-C(Baseline, Day 330)
- Percentage of Participants Achieving LDL-C < 100 mg/dL.(Day 330)
- Percentage of Participants Achieving LDL-C < 70 mg/dL(Day 330)
- Percentage of Participants Achieving LDL-C < 55 mg/dL(Day 330)
- Percent Change in Lipids and Other Lipoproteins From Baseline(Baseline, Day 330)
- Absolute Change in Lipids and Other Lipoproteins From Baseline(Baseline, Day 330)
- Percentage of Participants by Intensity of Lipid Lowering Therapy(Baseline, Day 330)
- Proportion of Days Covered by Medication(Up to 330 Days)
- LDL-C Measures of Variability - Standard Deviation(Day 90, Day 180, Day 270 and Day 330)
- LDL-C Measures of Variability - Coefficient of Variation(Day 90, Day 180, Day 270 and Day 330)