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
Studieoversikt
Status
Studietype
Registrering (Antatt)
Fase
- Ikke aktuelt
Kontakter og plasseringer
Studiekontakt
- Navn: Hai Gao, MD
- Telefonnummer: +86 13901015971
- E-post: gaohai1221@mail.ccmu.edu.cn
Studiesteder
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Beijing Municipality
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Beijing, Beijing Municipality, Kina, 100029
- Beijing Anzhen Hospital, Capital Medical University
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Ta kontakt med:
- Hai Gao, MD
- Telefonnummer: +86 13901015971
- E-post: gaohai1221@mail.ccmu.edu.cn
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Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
- Voksen
- Eldre voksen
Tar imot friske frivillige
Beskrivelse
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.
Studieplan
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: Randomisert
- Intervensjonsmodell: Parallell tildeling
- Masking: Enkelt
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
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Eksperimentell: 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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Aktiv komparator: 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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Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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Major Adverse Cardiovascular Events-4 (MACE-4)
Tidsramme: 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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Sekundære resultatmål
Resultatmål |
Tidsramme |
|---|---|
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All-cause mortality
Tidsramme: 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)
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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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Samarbeidspartnere og etterforskere
Sponsor
Studierekorddatoer
Studer hoveddatoer
Studiestart (Antatt)
Primær fullføring (Antatt)
Studiet fullført (Antatt)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Faktiske)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Ytterligere relevante MeSH-vilkår
Andre studie-ID-numre
- LIPID-2026-001
Plan for individuelle deltakerdata (IPD)
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