Status
Conditions
Treatments
About
To determine whether treating to an LDL-C target of 25 to <70 mg/dL is superior to an LDL-C target of 70 to <100 mg/dL with respect to major cardiovascular events (cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization) in patients aged ≥75 years with atherosclerotic cardiovascular disease (ASCVD).
To determine whether treating to an LDL-C target of 25 to <70 mg/dL is non-inferior to an LDL-C target of 70 to <100 mg/dL with respect to major safety events (hemorrhagic stroke, new-onset diabetes, muscle-related events, neurocognitive adverse events, new or recurrent cancer, cataract, or hepatic disorder [Alanine aminotransferase (ALT)/Aspartate aminotransferase (AST) >3× ULN, or total bilirubin >2× ULN]) in patients aged ≥75 years with ASCVD.
Full description
The benefits of LDL cholesterol-lowering treatment for the prevention of atherosclerotic cardiovascular disease (ASCVD) are well established. LDL-C lowering is associated with a significant reduction in major adverse cardiovascular events in a linear fashion, apparently without any plateau at low LDL-C levels. On the other hand, the degree to which LDL-C levels can be safely lowered remains unclear. It is still controversial whether lower LDL-C levels are associated with significant clinical adverse effects (e.g. new-onset diabetes mellitus or possibly hemorrhagic stroke) and long-term data are needed to address safety concerns.
It should be noted that the benefits and risks from LDL cholesterol lowering in older patients (age ≥75 years) remains debated because most randomized trials have explicitly excluded or enrolled few older adults. In clinical practice, the appropriate treatment target for LDL-C in patients ≥75 years of age with ASCVD remains uncertain. Current US and European cholesterol guidelines have no specific recommendations regarding the LDL-C treatment goal for older patients and noted that the level of evidence in older patients is low. Currently, there is no direct evidence from randomized clinical trials (RCTs) for the most appropriate treatment targets for LDL-C among patients ≥75 years of age with ASCVD in worldwide.
The TARGET OLD trial is a multicenter, open-label, parallel-group, event-driven, randomized, controlled trial with blinded end-point evaluation. Consecutive patients aged ≥75 years with ASCVD who meet the inclusion criteria and none of the exclusion criteria outlined above will be randomized in a 1:1 fashion to LDL-C target of 25 to <70 mg/dL or LDL-C target of 70 to <100 mg/dL. The proposed study will examine the comparative efficacy and safety of treating to an LDL-C target of 25 to <70 mg/dL compared with an LDL-C target of 70 to <100 mg/dL among patients aged 75 years or older with ASCVD. Our primary hypothesis is that, among such patients, targeting an LDL-C of 25 to less than 70 mg/dL is superior to a target of 70 to less than 100 mg/dL on reducing the risk of major adverse cardiovascular events (primary efficacy end point), while is non-inferior towards the composite of major safety outcomes (key secondary safety end point).
Prescription of lipid-lowering agents (drug and dosage up to the investigator according to the assigned target LDL-C level. Statin monotherapy or in combination with ezetimibe, PCSK9 inhibitor or other drugs were adjusted on the basis of the study-group assignment. Patients will follow-up at 1, 2, 4, 6, 12 months, and then every 6 months throughout 36 months with an evaluation of patients' lipid profiles, any cardiovascular events, safety and adverse events, muscle-related symptoms, quality of life (EQ-5D), and patient-reported cognition function (ECog scale). The trial will continue until 726 adjudicated primary endpoint events have occurred. We estimated that 4,200 patients would be needed to provide the necessary number of confirmed endpoints to test the study hypothesis. All analyses will be according to the intention-to-treat (ITT) principle.
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
Men or women ≥75 years of age
Diagnosis of clinical atherosclerotic cardiovascular disease (ASCVD) with one or more of the following:
Diagnosis of coronary heart disease (one or more of the following criteria must be satisfied):
Diagnosis of atherosclerotic cerebrovascular or carotid disease (one or more of the following criteria must be satisfied):
Diagnosis of atherosclerotic peripheral artery disease (one or more of the following criteria must be satisfied):
History of aorto-iliac or peripheral arterial intervention (catheter-based or surgical).
Prior non-traumatic amputation of a lower extremity due to peripheral artery disease
History of intermittent claudication and one or more of the following:
Baseline LDL-C level should be satisfied:
Signed written informed consent.
Exclusion criteria
Subject was clinically unstable:
Moderate to severe heart failure (New York Heart Association [NYHA] Functional Classification III or IV) or last known left ventricular ejection farction (LVEF) <40%.
Severe renal dysfunction, defined as creatinine clearance <30 mL/min or estimated glomerular filtration (eGFR) rate less than 30 ml/min/1.73 m2, or requirement for peritoneal dialysis or hemodialysis for renal insufficiency.
History of hemorrhagic stroke or unknown classified stroke.
Uncontrolled or recurrent ventricular tachycardia (such as ventricular fibrillation, recurrent and highly symptomatic ventricular tachycardia, complete heart block, atrial fibrillation with rapid ventricular response, or supraventricular tachycardia that are not controlled by medications).
Uncontrolled hypertension (greater than 180 mm Hg systolic and/or greater than 110 mm Hg diastolic at randomization visit).
History or clinical evidence of active liver disease or hepatic dysfunction, defined as alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3 × upper limit of normal (ULN), or total bilirubin > 2 × ULN.
Unexplained elevated creatine kinase (CK) concentration >5 × ULN or elevation due to known muscle disease.
Planned or expected cardiac surgery, PCI or carotid stenting, or planned major noncardiac surgery during the study period. If angiography or revascularization is planned, patients may be screened and enrolled after all such planned procedures are completed.
Active Malignancy (except nonmelanoma skin cancers, cervical in-situ carcinoma, breast ductal carcinoma in situ, or stage 1 prostate carcinoma) including those patients requiring surgery, chemotherapy, and/or radiation in the past 3 years.
Drug or alcohol abuse, and inability/unwillingness to abstain from drug abuse and excessive alcohol consumption during the study.
Severe, concomitant noncardiovascular disease that is expected to reduce life expectancy to <3 years
Currently receiving treatment in another investigational device or drug study, or less than 30 days since ending treatment on another investigational device or drug study(ies), or receiving other investigational agent(s)
Subject has received drugs via a systemic route that have known major interactions with background statin therapy (eg, itraconazole, ketoconazole, and other antifungal azoles, erythromycin, clarithromycin, or cyclosporine nefazodone) within 1 month prior to randomization or is likely to require such treatment during the study period.
Recipient of any major organ transplant (eg, lung, liver, heart, bone marrow, renal)
Subject likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures (eg, Clinical Outcome Assessments) to the best of the subject and investigator's knowledge.
Any uncontrolled or serious disease, or any medical or surgical condition (such as known active infection or major hematologic, renal, metabolic, gastrointestinal or endocrine dysfunction, or a chronic disease or infection [eg, HIV]), that may either interfere with participation in the clinical study and is not currently stable and appropriately managed in the judgment of the investigator, and/or put the subject at significant risk (according to investigator's judgment) if he/she participates in the clinical study.
Mental/psychological impairment/neurocognitive disorder, or any other reason to expect patient difficulty in complying with the requirements of the study or understanding the goal and potential risks of participating in the study
Primary purpose
Allocation
Interventional model
Masking
4,200 participants in 2 patient groups
Loading...
Central trial contact
Hao-Yu Wang, MD, PhD; Kefei Dou, MD, PhD
Data sourced from clinicaltrials.gov
Clinical trials
Research sites
Resources
Legal