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

The purpose of this study is to assess the effect on LDL-C of implementation of a systematic LDL-C management care pathway that includes initiation of inclisiran compared to usual care without inclisiran in participants with a recent hospitalization (inpatient/outpatient) for an acute coronary syndrome (ACS) with LDL-cholesterol ≥70 mg/dL despite receiving statin therapy.

Study Timeline

• Study First Submitted: 2021-04-30
• Study First Submitted QC: 2021-04-30
• Study First Posted: 2021-05-05
• Study Start: 2021-06-24
• Primary Completion: 2024-08-07
• Study Completion: 2024-08-07
• Status Verified: 2025-01
• Last Update Submitted: 2025-02-11
• Last Update Posted: 2025-02-13

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
Percentage (%) change in low-density lipoprotein cholesterol (LDL-C)	Baseline and Day 330	Inclisiran compared to usual care in reducing LDL-C \[percent change\] at Day 330 (Year 1)
Percentage (%) achieving change in low-density lipoprotein cholesterol (LDL-C) to <70 mg/dL	Baseline and Day 330	Inclisiran compared to usual care in achieving LDL-C reduction \<70 mg/dL \[percent achieved\] at Day 330 (Year 1)

Secondary Outcome Measures

Name	Time	Method
Absolute change from baseline in low-density lipoprotein cholesterol (LDL-C)	Baseline to Day 330	Inclisiran compared to usual care in reducing LDL-C \[absolute change\] at Day 330 (Year 1)
Average percent change from baseline in low-density lipoprotein cholesterol (LDL-C) levels to each post-baseline visit	Baseline, Day 330	Inclisiran compared to usual care on average percent change from baseline in LDL-C levels after Day 90 and up to Day 330
Average absolute change from baseline in low-density lipoprotein cholesterol (LDL-C) levels to each post-baseline visit	Baseline, Day 330	Inclisiran compared to usual care on average absolute change from baseline in LDL-C levels after Day 90 and up to Day 330
Achieving ≥50% reduction from baseline in low-density lipoprotein cholesterol (LDL-C) (yes, no)	Baseline, Day 330	Inclisiran compared to usual care on achieving ≥50% reduction from baseline to Day 330
Percentage of participants achieving low-density lipoprotein cholesterol (LDL-C) targets (LDL-C <100 mg/dL among the subset of participants with LDL-C ≥100 mg/dL at baseline, and LDL-C <55 mg/dL)	Baseline, Day 330	Inclisiran compared to usual care on achieving LDL-C \<100 mg/dL (subset of LDL-C ≥100 mg/dL at baseline) in LDL-C \<55 mg/dL to Day 330
Percent change in apolipoprotein B, very low density lipoprotein, high density lipoprotein cholesterol, lipoprotein (a), non-high density lipoprotein cholesterol, and total cholesterol	Baseline and Day 330	Inclisiran compared to placebo in reducing Apo B, very low density lipoprotein (VLDL), high density lipoprotein cholesterol (HDL-C), lipoprotein (a) \[Lp(a)\], non-high density lipoprotein cholesterol (non-HDL-C), and total cholesterol over time
Absolute change in apolipoprotein B, very low density lipoprotein, high density lipoprotein cholesterol, lipoprotein (a), non-high density lipoprotein cholesterol, and total cholesterol	Baseline and Day 330	Inclisiran compared to placebo in reducing Apo B, very low density lipoprotein (VLDL), high density lipoprotein cholesterol (HDL-C), lipoprotein (a) \[Lp(a)\], non-high density lipoprotein cholesterol (non-HDL-C), and total cholesterol over time
Measurement of the intensity of lipid lowering therapy (dose decrease, increase or no change)	Baseline and Day 330	Inclisiran compared to usual care on intensity of lipid lowering therapy over time
Percentage of participants discontinuing statin therapy (i.e., no statin use ≥30 days before the end-of-study visit)	Baseline and Day 330	Inclisiran compared to usual care on discontinuation of statin therapy from baseline to Day 330

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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