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NCT Number: NCT07615296

Target-Oriented Strategy of Ultra-Low LDL-C (<1.0 vs. 1.0-1.39 mmol/L) in Extreme-High-Risk ASCVD Patients: Clinical Benefit, Safety and Cost-Effectiveness Assessment

The goal of this clinical trial is to learn whether an ultra-low LDL-C target (<1.0 mmol/L) can improve clinical outcomes compared with a moderately low LDL-C target (1.0-1.39 mmol/L) in Chinese patients with extreme-high-risk atherosclerotic cardiovascular disease (ASCVD). It also aims to evaluate long-term safety and cost-effectiveness, and explore potential benefit subgroups and underlying mechanisms. The main questions it aims to answer are:

Does an LDL-C target <1.0 mmol/L reduce major adverse cardiovascular events (MACE-4: cardiovascular death, non-fatal myocardial infarction, non-fatal ischemic stroke, urgent coronary revascularization) compared with a target of 1.0-1.39 mmol/L?What are the long-term safety risks including cognitive decline, hemorrhagic stroke, new-onset diabetes, new malignancies and severe adverse drug reactions under different LDL-C targets?Researchers will compare participants receiving an LDL-C target <1.0 mmol/L with those receiving a target of 1.0-1.39 mmol/L to see if the ultra-low LDL-C strategy provides better clinical benefit with acceptable safety and economic value.

Participants will:

Receive lipid-lowering therapy following a mandatory titration-maintenance-off-target correction algorithm according to their assigned LDL-C target Undergo routine follow-up every 3 months, cognitive assessment every 6 months, and comprehensive annual re-examinations for a median of 2 years and up to 5 years Have centralized blinded lipid testing and endpoint adjudication by an independent Clinical Event Committee

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Key information

Conditions

Atherosclerotic Cardiovascular Disease (ASCVD) Arterial Occlusive Diseases Arteriosclerosis Atherosclerosis Cardiovascular Diseases Vascular Diseases

Age range

18 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Beijing Anzhen Hospital, Capital Medical University

Beijing, Beijing Municipality, 100029, China

Location contact

Hai Gao, MD

CONTACT

[email protected]

+86 13901015971

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Aged 18-80 years, any sex.
  • Diagnosed with ultra-high-risk ASCVD per 2023 Chinese Lipid Guidelines: either ≥2 major ASCVD events within 24 months, or 1 major ASCVD event plus ≥2 high-risk factors (diabetes, multi-vessel disease, premature CHD family history, elevated Lp(a), hypertension).
  • LDL-C ≥1.0 mmol/L after ≥4-week maximum-tolerated statin plus ezetimibe therapy, confirmed by central laboratory.
  • Able to complete follow-up and examinations; no severe hepatic/renal dysfunction.
  • Voluntary participation with written informed consent.

Exclusion criteria

  • Hypersensitivity or intolerance to statins, ezetimibe, or PCSK9 inhibitors.
  • Hemorrhagic stroke, active bleeding, severe trauma or major surgery within 6 months before enrollment.
  • Malignancy (expected survival <3 years), severe liver/kidney disease, or autoimmune disease.
  • Cognitive impairment (MoCA <20) or psychiatric disorders precluding assessment cooperation.
  • Pregnant, breastfeeding, or planning pregnancy during the trial.
  • Participation in other clinical trials or use of other lipid-lowering drugs within 3 months.
  • Poor compliance or other conditions judged by investigators to interfere with the study.

Treatment and study plan

Lipid-lowering therapy targeting LDL-C <1.0 mmol/L

Drug

Statin-ezetimibe-based lipid-lowering therapy with mandatory titration-maintenance-off-target correction algorithm. PCSK9 inhibitor is sequentially added and dose-adjusted based on centralized blinded lipid test results to achieve LDL-C level <1.0 mmol/L.

Lipid-lowering therapy targeting LDL-C 1.0-1.39 mmol/L

Drug

Standard statin-ezetimibe lipid-lowering therapy. Mandatory dose reduction (discontinue ezetimibe → halve statin → discontinue statin) will be performed if LDL-C drops below 1.0 mmol/L, to maintain LDL-C within 1.0-1.39 mmol/L.

Primary outcomes

  1. Major Adverse Cardiovascular Events-4 (MACE-4)

    Time frame: Median 2 years, up to 5 years from randomization

    Composite endpoint including cardiovascular death, non-fatal myocardial infarction, non-fatal ischemic stroke, and urgent coronary revascularization.

Secondary outcomes

  1. All-cause mortality

    Time frame: Median 2 years, up to 5 years post-randomization

  2. Major Adverse Cardiovascular Events-3 (MACE-3)

    Time frame: Median 2 years, up to 5 years post-randomization

  3. individual components of MACE-4

    Time frame: Median 2 years, up to 5 years post-randomization

  4. LDL-C target achievement rate

    Time frame: Median 2 years, up to 5 years post-randomization

Study contacts

Contact information is provided by the study sponsor or research team.

Hai Gao, MD

CONTACT

[email protected]

+86 13901015971

Sponsors and collaborators

Lead sponsor

Beijing Anzhen Hospital

Other

Registry information

Official study title

Target-Oriented Strategy of Ultra-Low LDL-C Goal in Extreme-High-Risk ASCVD Patients (<1.0 vs. 1.0-1.39 mmol/L): Clinical Benefit, Safety and Cost-Effectiveness Assessment- A Multicenter, Prospective, Randomized, Open-Label, Blinded-Endpoint Adaptive Trial

Acronym: TARGET-EXTREME

Important dates

Study start
2027
Primary completion
2029
Study completion
2031
First posted
May 29, 2026
Registry last updated
May 29, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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