LDL Cholesterol TARGETs in OLDer Patients (Age≥75 Years) With ASCVD (TARGET OLD)

NCT05765370 | Recruiting

• 1 other identifier: 2022-1879
• Study Type: interventional
• Target: 4,200
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Atherosclerotic Cardiovascular Disease; Older Patients; LDL Cholesterol

Keywords

LDL-C target; Atherosclerotic Cardiovascular Disease; Older patients; Age≥75 years; Lipid-lowering therapy; Stain; PCSK9 inhibitor

Outcome Measures

Primary Outcomes (1)

• Time to first occurrence of major cardiovascular events (composite of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, coronary revascularization)

  The primary endpoint measure was the number of patients with a first occurrence of adjudicated composite of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization during the follow-up period.

  From randomization until study completion (until 726 adjudicated primary endpoint events have occurred); for approximately a median follow-up of 42 months

Secondary Outcomes (12)

• Time to first occurrence of major safety events (composite of hemorrhagic stroke, new-onset diabetes, muscle-related events, neurocognitive adverse events, new or progressive cancer, cataract, or hepatic disorder).

  From randomization until study completion (until 726 adjudicated primary endpoint events have occurred); for approximately a median follow-up of 42 months

• Time to first occurrence of composite endpoint of cardiovascular death, myocardial infarction, stroke, or coronary revascularization.

  From randomization until study completion (until 726 adjudicated primary endpoint events have occurred); for approximately a median follow-up of 42 months.

• Time to first occurrence of composite endpoint of cardiovascular death, myocardial infarction, or stroke.

  From randomization until study completion (until 726 adjudicated primary endpoint events have occurred); for approximately a median follow-up of 42 months.

• Time to first occurrence of composite endpoint of all-cause death, myocardial infarction, or stroke.

  From randomization until study completion (until 726 adjudicated primary endpoint events have occurred); for approximately a median follow-up of 42 months.

• Time to first occurrence of composite endpoint of cardiovascular death or myocardial infarction.

  From randomization until study completion (until 726 adjudicated primary endpoint events have occurred); for approximately a median follow-up of 42 months.

Other Outcomes (2)

• Health-related Quality-of-life outcome

  Baseline, 30 days, 6 months, 1 year, and then every 6 months until study completion (726 adjudicated primary endpoint events have occurred)

• Patient-reported cognition function

  Baseline, 30 days, 6 months, 1 year, and then every 6 months until study completion (726 adjudicated primary endpoint events have occurred).

Study Arms (2)

LDL-C Lower-Target Group (25mg/dL≤ LDL-C<70mg/dL)

EXPERIMENTAL

Participants randomized into the LDL-C lower-target arm will have a goal of 25mg/dL≤ LDL-C\<70mg/dL. Prescription of lipid-lowering agents (drug and dosage) were initiated or adjusted on the basis of the investigator according to the assigned target LDL-C level.

Procedure: Achieving a Target LDL-C level of 25mg/dL≤ LDL-C<70mg/dL

LDL-C Higher-Target Group (70mg/dL≤ LDL-C<100mg/dL)

ACTIVE COMPARATOR

Participants randomized into the LDL-C lower-target arm will have a goal of 70mg/dL≤ LDL-C\<100mg/dL. Prescription of lipid-lowering agents (drug and dosage) were initiated or adjusted on the basis of the investigator according to the assigned target LDL-C level.

Procedure: Achieving a Target LDL-C level of 70mg/dL≤ LDL-C<100mg/dL

Interventions

Achieving a Target LDL-C level of 25mg/dL≤ LDL-C<70mg/dL PROCEDURE

Investigators initiated or adjusted lipid-lowering agents (drug and dosage) to achieve the target of 25mg/dL≤ LDL-C\<70mg/dL. The protocol encouraged, but did not mandate, the initiation of moderate-intensity statin therapy for secondary prevention with the evaluation of the potential for ASCVD risk reduction, adverse effects, and drug-drug interactions, as well as patient frailty and patient preferences. Statin monotherapy or in combination with ezetimibe, PCSK9 inhibitor or other drugs were adjusted on the basis of LDL-C levels. At each follow-up visit, the investigators should verify whether the target LDL-C has been obtained. If the target level of LDL cholesterol was achieved, it is reasonable to continue to monitor adherence to lifestyle modifications, medication, and ongoing LDL-C response to therapy. If the target level of LDL cholesterol was not achieved, adjustment of the type and dose regimen of statin, or the additional of a nonstatin agent should be considered.

LDL-C Lower-Target Group (25mg/dL≤ LDL-C<70mg/dL)

Achieving a Target LDL-C level of 70mg/dL≤ LDL-C<100mg/dL PROCEDURE

Investigators initiated or adjusted lipid-lowering agents (drug and dosage) to achieve the target of 70mg/dL≤ LDL-C\<100mg/dL. The protocol encouraged, but did not mandate, the initiation of moderate-intensity statin therapy for secondary prevention with the evaluation of the potential for ASCVD risk reduction, adverse effects, and drug-drug interactions, as well as patient frailty and patient preferences. Statin monotherapy or in combination with ezetimibe, PCSK9 inhibitor or other drugs were adjusted on the basis of LDL-C levels. At each follow-up visit, the investigators should verify whether the target LDL-C has been obtained. If the target level of LDL cholesterol was achieved, it is reasonable to continue to monitor adherence to lifestyle modifications, medication, and ongoing LDL-C response to therapy. If the target level of LDL cholesterol was not achieved, adjustment of the type and dose regimen of statin, or the additional of a nonstatin agent should be considered.

LDL-C Higher-Target Group (70mg/dL≤ LDL-C<100mg/dL)

Eligibility Criteria

• Age: 75 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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):
• Hospitalization for acute coronary syndrome
• Treatment or hospitalization for stable angina pectoris with documented ischemia on invasive or noninvasive testing
• History of myocardial infarction
• History of coronary revascularization procedure (eg, percutaneous coronary intervention \[PCI\] or coronary artery bypass graft surgery \[CABG\])
• Invasive diagnostic coronary angiography indicating \>50% stenosis in at least one major epicardial coronary artery or CT-imaging (eg, CCTA/MDCT) evidence of coronary atherosclerosis (\>50% stenosis in at least two major epicardial coronary artery)
• Diagnosis of atherosclerotic cerebrovascular or carotid disease (one or more of the following criteria must be satisfied):
• History of ischemic stroke or transient ischemic attack (TIA) confirmed by symptoms with a documented ischemic lesion on CT or MRI in the cerebral regions corresponding to the symptoms;
• Documented intracranial atherosclerotic stenosis on the basis of conventional cerebral angiography, magnetic resonance angiography, CT angiography, transcranial doppler ultrasound, and high-resolution MRI;
• Symptomatic carotid artery disease with ≥50% carotid arterial stenosis;
• Asymptomatic carotid artery disease with ≥70% carotid arterial stenosis per angiography or duplex ultrasound;
• History of carotid revascularization (catheter-based or surgical).
• Diagnosis of atherosclerotic peripheral artery disease (one or more of the following criteria must be satisfied):

You may not qualify if:

• Subject was clinically unstable:
• Hypotension, defined as sustained systolic blood pressure of \<90 mmHg due to cardiac failure with associated symptoms;
• Unstable or severe pulmonary edema/decompensated congestive heart failure;
• Acute mitral regurgitation or acute ventricular septal defect;
• Cardiogenic shock and/or need for mechanical/pharmacologic hemodynamic support
• Ongoing Non-STEMI with biomarkers (cardiac troponin) still rising
• Recent STEMI (≤7 days prior to randomization)
• Recurrent symptoms of cardiac ischemia
• 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.

Sponsors & Collaborators

• China National Center for Cardiovascular Diseases: lead

Study Sites (1)

Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College

Beijing, Beijing Municipality, 100037, China

RECRUITING

MeSH Terms

Conditions

Atherosclerosis

Condition Hierarchy (Ancestors)

Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Kefei Dou, MD, PhD

  Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing

  PRINCIPAL INVESTIGATOR

• Hao-Yu Wang, MD, PhD

  Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kefei Dou, MD, PhD

CONTACT

+86-10-13801032912; drdoukefei@126.com

Hao-Yu Wang, MD, PhD

CONTACT

+86-10-15810671272; wanghaoyu@fuwai.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Participants and study investigators were aware of the study-group assignments, but outcome adjudicators were not. All potential cardiovascular events and safety events were adjudicated according to prespecified criteria by an independent clinical events committee whose members were unaware of the trial-group assignments.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 1, 2023
• First Posted: March 13, 2023
• Study Start: March 24, 2023
• Primary Completion (Estimated): September 24, 2026
• Study Completion (Estimated): December 24, 2026
• Last Updated: April 10, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)