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
調査の概要
状態
研究の種類
入学 (推定)
段階
- 適用できない
連絡先と場所
研究連絡先
- 名前：Hai Gao, MD
- 電話番号：+86 13901015971
- メール：gaohai1221@mail.ccmu.edu.cn
研究場所
-
-
Beijing Municipality
-
Beijing、Beijing Municipality、中国、100029
- Beijing Anzhen Hospital, Capital Medical University
-
コンタクト：
- Hai Gao, MD
- 電話番号：+86 13901015971
- メール：gaohai1221@mail.ccmu.edu.cn
-
-
参加基準
適格基準
就学可能な年齢
- 大人
- 高齢者
健康ボランティアの受け入れ
説明
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.
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：独身
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
実験的：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.
|
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.
|
|
アクティブコンパレータ：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.
|
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.
|
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Major Adverse Cardiovascular Events-4 (MACE-4)
時間枠：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.
|
Median 2 years, up to 5 years from randomization
|
二次結果の測定
結果測定 |
時間枠 |
|---|---|
|
All-cause mortality
時間枠：Median 2 years, up to 5 years post-randomization
|
Median 2 years, up to 5 years post-randomization
|
|
Major Adverse Cardiovascular Events-3 (MACE-3)
時間枠：Median 2 years, up to 5 years post-randomization
|
Median 2 years, up to 5 years post-randomization
|
|
individual components of MACE-4
時間枠：Median 2 years, up to 5 years post-randomization
|
Median 2 years, up to 5 years post-randomization
|
|
LDL-C target achievement rate
時間枠：Median 2 years, up to 5 years post-randomization
|
Median 2 years, up to 5 years post-randomization
|
協力者と研究者
スポンサー
研究記録日
主要日程の研究
研究開始 (推定)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- LIPID-2026-001
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。