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 (TARGET-EXTREME)
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
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
연구 개요
상태
연구 유형
등록 (추정된)
단계
- 해당 없음
연락처 및 위치
연구 연락처
- 이름: Hai Gao, MD
- 전화번호: +86 13901015971
- 이메일: gaohai1221@mail.ccmu.edu.cn
연구 장소
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Beijing Municipality
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Beijing, Beijing Municipality, 중국, 100029
- Beijing Anzhen Hospital, Capital Medical University
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연락하다:
- Hai Gao, MD
- 전화번호: +86 13901015971
- 이메일: gaohai1221@mail.ccmu.edu.cn
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참여기준
자격 기준
공부할 수 있는 나이
- 성인
- 고령자
건강한 자원 봉사자를 받아들입니다
설명
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.
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위
- 중재 모델: 병렬 할당
- 마스킹: 하나의
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
|---|---|
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실험적: Ultra-low LDL-C target group
Participants receive statin-ezetimibe-based lipid-lowering therapy with mandatory titration algorithm, adding PCSK9 inhibitor sequentially to achieve LDL-C <1.0 mmol/L.
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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.
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활성 비교기: Moderate-low LDL-C target group
Participants maintain statin-ezetimibe therapy; dose reduction is enforced if LDL-C <1.0 mmol/L to keep level within 1.0-1.39
mmol/L.
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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.
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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Major Adverse Cardiovascular Events-4 (MACE-4)
기간: Median 2 years, up to 5 years from randomization
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Composite endpoint including cardiovascular death, non-fatal myocardial infarction, non-fatal ischemic stroke, and urgent coronary revascularization.
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Median 2 years, up to 5 years from randomization
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2차 결과 측정
결과 측정 |
기간 |
|---|---|
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All-cause mortality
기간: Median 2 years, up to 5 years post-randomization
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Median 2 years, up to 5 years post-randomization
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Major Adverse Cardiovascular Events-3 (MACE-3)
기간: Median 2 years, up to 5 years post-randomization
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Median 2 years, up to 5 years post-randomization
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individual components of MACE-4
기간: Median 2 years, up to 5 years post-randomization
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Median 2 years, up to 5 years post-randomization
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LDL-C target achievement rate
기간: Median 2 years, up to 5 years post-randomization
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Median 2 years, up to 5 years post-randomization
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공동 작업자 및 조사자
연구 기록 날짜
연구 주요 날짜
연구 시작 (추정된)
기본 완료 (추정된)
연구 완료 (추정된)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (실제)
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
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