Management of LDL-cholesterol With Inclisiran + Usual Care Compared to Usual Care Alone in Participants With a Recent Acute Coronary Syndrome

Phase 3

Completed

Conditions: Acute Coronary Syndrome

Interventions: Drug: Inclisiran

Registration Number: NCT04873934

Lead Sponsor: Novartis Pharmaceuticals

Brief Summary: The purpose of this study is to study the effectiveness of implementation of a systematic LDL-C management pathway including treatment with inclisiran in participants who have experienced a recent acute coronary syndrome (ACS) and have an increased LDL-cholesterol (≥70 mg/dL) despite being treated with a statin drug.

Detailed Description: This was a randomized, parallel-group, open-label, multicenter, 1-year (30-day Screening Period and 330-day Treatment Period) study comparing an LDL-C management strategy including inclisiran + usual care to usual care alone. Approximately 384 participants were planned to be randomized 1:1 to aggressive LDL-C management with inclisiran + usual care (intervention arm) (3 inclisiran doses) or usual care (control arm). Usual care could have included addition of ezetimibe, bempedoic acid, PCSK9-inhibiting monoclonal antibodies, and/or commercially available inclisiran

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 400

Inclusion Criteria

Recent Acute Coronary Syndrome (in-patient/out-patient) within 5 weeks of screening
Serum LDL-C ≥70 mg/dL or non-HDL-C ≥100 mg/dL
Fasting triglycerides <4.52 mmol/L (<400 mg/dL) at screening
Calculated glomerular filtration rate >20 mL/min by estimated glomerular filtration rate (eGFR)
Participants are required to be discharged on statin therapy, or have documented statin intolerance, as determined by the investigator, following hospitalization for an ACS. Statin intolerant participants are eligible if they had intolerable side effects on at least 2 different statins, including one at the lowest standard dose

Exclusion Criteria

New York Heart Association (NYHA) class IIIb or IV heart failure or last known left ventricular ejection fraction <25%.
Significant cardiac arrhythmia within 3 months prior to randomization that is not controlled by medication or via ablation at the time of screening.
Severe concomitant non-cardiovascular disease that carries the risk of reducing life expectancy to less than 2 years.
Treatment with other investigational products or devices within 30 days or five half˗lives of the screening visit, whichever is longer.
Planned use of other investigational products or devices during the course of the study.
Treatment with monoclonal antibodies directed towards PCSK9 within 90 days of screening.
Recurrent ACS event within 2 weeks prior to randomization.
Coronary angiography and revascularization procedure (percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) surgery) performed within 2 weeks prior to the randomization visit or planned after randomization.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Inclisiran with Usual Care	Inclisiran	Inclisiran sodium 300 mg / 1.5 ml (equivalent to 284 mg of inclisiran)

Primary Outcome Measures

Name	Time	Method
Percent Change From Baseline to Day 330 in LDL-C	Baseline and Day 330	Percent change from baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Day 330
Achievement of LDL-C < 70 mg/dL at Day 330	Day 330	Percentage of participants achieving Low-Density Lipoprotein Cholesterol (LDL-C) \< 70 mg/dL at Day 330

Secondary Outcome Measures

Name	Time	Method
Absolute Change From Baseline in LDL-C	Baseline, Day 90, Day 270 and Day 330	Absolute change from baseline in low-density lipoprotein cholesterol (LDL-C) by visit
Average Percent Change From Baseline in LDL-C Levels	Baseline, from Day 90 to Day 330	Average percent change from baseline in low-density lipoprotein cholesterol (LDL-C) levels to each post-baseline visit
Average Absolute Change From Baseline in LDL-C Levels	Baseline, From Day 90 to Day 330	Average absolute change from baseline in low-density lipoprotein cholesterol (LDL-C) levels to each post-baseline visit
Achieving ≥50% Reduction From Baseline in LDL-C	Baseline, Day 330	Percentage of participants achieving ≥50% reduction from baseline in low-density lipoprotein cholesterol (LDL-C) at Day 330
Achieving LDL-C < 100 mg/dL and LDL-C < 55 mg/dL	Day 330	Percentage of participants achieving low-density lipoprotein cholesterol (LDL-C) \<100 mg/dL (among the subset of participants with baseline LDL-C \>= 100 mg/dL) and LDL-C \< 55 mg/dL at Day 330
Percent Change in Lipids and Other Lipoproteins From Baseline to Day 330	Baseline and Day 330	Percent change in apolipoprotein B, very-low-density lipoprotein (VLDL), non-high-density lipoprotein cholesterol (non-HDL-C), total cholesterol, lipoprotein(a) (Lp\[a\]), HDL-C and triglycerides from baseline to Day 330
Absolute Change in Lipids and Other Lipoproteins From Baseline to Day 330	Baseline and Day 330	Absolute change in apolipoprotein B, very-low-density lipoprotein (VLDL), non-high-density lipoprotein cholesterol (non-HDL-C), total cholesterol, HDL-C and triglycerides from baseline to Day 330
Absolute Change in Lp[a] From Baseline to Day 330	Baseline and Day 330	Absolute change in lipoprotein(a) (Lp\[a\]) from baseline to Day 330
Intensity of Lipid Lowering Therapy	Baseline and Day 330	Percentage of participants by intensity of lipid lowering therapy (dose decrease, increase or no change)
Proportion of Days Covered	Baseline through last date of participation, up to 330 Days	Total number of days on either statin, ezetimibe, or PCSK9 inhibiting monoclonal antibody therapies divided by total number of study days. If a participant did not take any of the 3 medications, then the total number of days was assumed to be zero.
Discontinuation of Statin Therapy	Baseline and Day 330	Percentage of participants discontinuing statin therapy. Discontinuation of statin therapy was defined as no statin use ≥ 30 days before the end-of-study visit. Participants for whom it could not be ascertained that they were on statin therapy at the end of study or who discontinued from the study early were assumed to have discontinued statin therapy.

Trial Locations

Locations (88): Northeast Arkansas Baptist Clinic
🇺🇸
Jonesboro, Arkansas, United States
Central Cardiology Medical Center
🇺🇸
Bakersfield, California, United States
The Heart Group Cardiovascular Associates Inc
🇺🇸
Fresno, California, United States
Mission Heritage Medical Group
🇺🇸
Mission Viejo, California, United States
Northbay Clinical Research LLC
🇺🇸
Santa Rosa, California, United States
Clinnova Research Solutions
🇺🇸
Torrance, California, United States
Harbor-UCLA Medical Center
🇺🇸
Torrance, California, United States
Interv Cardiology Med Grp
🇺🇸
West Hills, California, United States
Aurora Denver Cardiology Associates
🇺🇸
Aurora, Colorado, United States
Colorado Springs Cardiology
🇺🇸
Colorado Springs, Colorado, United States
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Northeast Arkansas Baptist Clinic
🇺🇸Jonesboro, Arkansas, United States