Status and phase
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About
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.
Full 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.
Enrollment
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Volunteers
Inclusion and exclusion criteria
Participants eligible for inclusion in this study must meet all of the following criteria:
Signed informed consent must be obtained prior to participation in the study
Males and females ≥18 years of age
History of ASCVD, documented by hospital records, claims data and/or prior laboratory/imaging assessments a Coronary heart disease (CHD):
Serum LDL-C ≥70 mg/dL or non-HDL-C ≥100 mg/dL
Fasting triglyceride <5.65 mmol/L (<500 mg/dL) at screening
Calculated glomerular filtration rate >30 mL/min by estimated glomerular filtration rate (eGFR) using standardized local clinical methodology
Participants should be on maximally tolerated statin therapy, as determined by the investigator, with no immediate plans to modify lipid lowering therapies. Statin intolerant patients are eligible if they had documented side effects on at least 2 different statins, including one at the lowest standard dose
Participants must be willing and able to give informed consent before initiation of any study related procedures and willing to comply with all required study procedures
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:
Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy or tubal ligation at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential.
Known history of alcohol and/or drug abuse within the last 5 years (occasional casual users of illicit drugs in the opinion of the investigators are not excluded)
Treatment with other investigational products or devices within 30 days or five half-lives of the screening visit, whichever is longer
History of hypersensitivity to any of the study treatments or its excipients or to drugs of similar chemical classes
Planned use of other investigational products or devices during the course of the study
Any condition that according to the investigator could interfere with the conduct of the study, such as but not limited to:
Previous or current treatment (within 90 days of screening) with monoclonal antibodies directed towards PCSK9 or ezetimibe
Active liver disease defined as any known current infectious, neoplastic, or metabolic pathology of the liver or alanine aminotransferase (ALT) elevation >3x ULN, aspartate aminotransferase (AST) elevation >3x ULN, or total bilirubin elevation >2x ULN (except patients with Gilbert's syndrome) at screening confirmed by a repeat measurement at least one week apart
Primary purpose
Allocation
Interventional model
Masking
450 participants in 2 patient groups
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Central trial contact
Novartis Pharmaceuticals; Novartis Pharmaceuticals
Data sourced from clinicaltrials.gov
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