Clinical trial NCT06014060: 24 Versus 12-Month Dual Antiplatelet Therapy After Drug-Eluting Stent in Patients With Elevated Lipoprotein(a) Levels: A Prospective, Multicenter, Double-Blind, Placebo-Controlled Randomized Trial
Official title: 24 Versus 12-Month Dual Antiplatelet Therapy After Drug-Eluting Stent in Patients With Elevated Lipoprotein(a) Levels: A Prospective, Multicenter, Double-Blind, Placebo-Controlled Randomized Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Elevated Lipoprotein(a) Level
Coronary Artery Disease
Drug-Eluting Stent
Dual Antiplatelet Therapy
Keywords: Lipoprotein(a)
Coronary Artery Disease
Drug-Eluting Stent
Percutaneous Coronary Intervention
Dual Antiplatelet Therapy
Lead sponsor: China National Center for Cardiovascular Diseases
Sponsor class: OTHER_GOV
First posted: 2023-08-28
Enrollment: 3300
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 1. Main objective Among patients with elevated Lp(a) levels (\>30mg/dL) who did not experience cardiovascular events or BARC type 2, 3, or 5 bleeding within 12 months after PCI and DES implantation, was it possible to reduce the primary adverse cardiovascular and cerebrovascular events (a composite endpoint consisting of all-cause death, non-fatal myocardial infarction, and stroke) by extending the duration of DAPT (24 months) compared to the standard duration (12 months)? (Efficacy test)
2. Secondary Objectives Key secondary research objective: Among patients with elevated Lp(a) levels (\> 30mg/dL) who underwent PCI and received DES implantation within 12 months after the procedure, and who did not experience cardiovascular events or BARC type 2, 3, or 5 bleeding, whether extending the DAPT duration (24 months) compared to the standard DAPT duration (12 months) does not result in an increase in clinical net adverse events (a composite endpoint consisting of all-cause death, non-fatal myocardial infarction, stroke, and BARC type 3 or 5 bleeding) compared to the standard DAPT duration. (Non-inferiority test) Other secondary research objectives: To evaluate the differences in the incidence of the composite endpoint consisting of BARC type 3 or 5 bleeding (the primary safety endpoint) between extending the DAPT duration (24 months) and the standard DAPT duration (12 months); the differences in the incidence of the composite endpoint consisting of cardiovascular death and myocardial infarction; the differences in the incidence of the composite endpoint consisting of all-cause death and myocardial infarction; the differences in the incidence of stent thrombosis; the differences in the incidence of any myocardial infarction; the differences in the incidence of target vessel myocardial infarction; the differences in the incidence of stroke; the differences in the incidence of ischemic stroke; the differences in the incidence of hemorrhagic stroke; the differences in the incidence of cardiovascular death; the differences in the incidence of all-cause death; the differences in the incidence of repeat revascularization; the differences in the incidence of target vessel revascularization; the differences in the incidence of BARC type 2, 3, or 5 bleeding; the differences in the incidence of any bleeding.

Detailed description: Lp(a) levels play an important role in predicting subsequent ischemic events in patients with established coronary artery disease (CAD), especially those who underwent PCI. However, there are still no approved pharmacologic therapies that specifically target high Lp(a) levels.

DAPT consisting of aspirin and a P2Y12 receptor inhibitor represents the cornerstone of pharmacological treatment aimed at preventing thrombotic complications after PCI. Considering that Lp(a) has a prothrombotic effect through its inactive, plasminogen-like protease domain on apo(a), the investigators speculate that prolonged DAPT may have a beneficial effect on reducing future ischemic events in patients with elevated Lp(a) levels after PCI. Some observational studies revealed that DAPT \> 1 year was significantly associated with lower risk of cardiovascular events compared with DAPT ≤ 1 year in patients with elevated Lp(a) levels who were event-free at 1 year after PCI with DES. However, the relative efficacy and safety of prolonged DAPT versus standard DAPT in this high-risk population has never been assessed in randomized controlled trials (RCTs).

The DAPT-Lp(a) trial is a multicenter, parallel-group, randomized controlled trial with blinded end-point evaluation. Consecutive patients with Lp(a) levels\>30mg/dL who meet the inclusion criteria and none of the exclusion criteria will be randomized in a 1:1 fashion to 24-month DAPT group or 12-month DAPT group. The investigators hypothesise that, in patients with Lp(a) levels \>30mg/dL who were event-free at 1 year after PCI with DES, 24-month DAPT is superior to 12-month DAPT with respect to major adverse cardiovascular and cerebrovascular events (primary end point), while it is non-inferior to 12-month DAPT with respect to net adverse clinical events (key secondary end point).

The investigators estimated that 3,300 patients would be needed to provide the necessary number of confirmed endpoints to test the study hypothesis. Patients will be followed up at 3, 6, 9, 12 months after randomization. All analyses will be performed according to the intention-to-treat (ITT) principle.

Eligibility criteria: Inclusion Criteria:

1. Male or nonpregnant female between 18-75 years;
2. Subjects with Lp(a) levels \> 30mg/dL before percutaneous coronary intervention (PCI);
3. PCI procedure with drug-eluting stent (DES) implantation and no cardiovascular events or BARC type 2, 3, or 5 bleeding events occurring within 12 months after the procedure
4. Subjects (or legal guardian) understand the trial requirements and the treatment procedures and provides written informed;

Exclusion Criteria:

1. Subjects with Lp(a) \< 30mg/dL or Lp(a) level unavailable before PCI;
2. Subjects who experience adverse cardiovascular events (death, myocardial infarction, stent thrombosis, stroke, repeat coronary revascularization, or Bleeding Academic Research Consortium \[BARC\] type 2, 3 or 5 bleeding) within 1-year after PCI;
3. BARC type 2, 3, or 5 bleeding occurred before PCI
4. Unable to tolerate DAPT therapy or anticoagulant therapy at the same time, long-term use of non-steroidal anti-inflammatory drugs is required Or glucocorticoids;
5. Discontinuation of DAPT for ≥14 days for planned surgical procedures in the next 12 months;
6. Systolic blood pressure \< 90mmHg for \> 30 minutes accompanied by hypoperfusion symptoms or systolic blood pressure ≥ 90mmHg is maintained with mechanical/pharmacologic hemodynamic support;
7. Persistent symptoms of myocardial ischemia;
8. Moderate to severe heart failure (New York Heart Association \[NYHA\] Functional Classification III or IV) or last known left ventricular ejection fraction (LVEF) \< 40%;
9. Severe valvular heart disease, myocarditis or cardiomyopathy;
10. Severe hepatic insufficiency (ALT or AST \> 3 times upper limit of normal, total bilirubin \> 2.5 times upper limit of normal);
11. Severe renal dysfunction, defined as creatinine clearance \<30 mL/min or estimated glomerular filtration (eGFR) rate less than 30 ml/min/1.73m2, or requirement for peritoneal dialysis or hemodialysis for renal insufficiency;
12. Severe acute or chronic infectious disease;
13. History of severe rheumatic immune disease or malignant tumor;
14. Currently receiving treatment in another investigational device or drug study, or less than 30 days since ending treatment on another investigational device or drug study(ies), or receiving other investigational agent(s);
15. Drug or alcohol abuse, and inability/unwillingness to abstain from drug abuse and excessive alcohol consumption during the study;
16. Recipient of any major organ transplant (eg, lung, liver, heart, bone marrow, renal);
17. Known significant active and uncontrolled disease, or any medical, physical condition, as judged by the investigator Or surgical status, may interfere with participation in this study
18. Mental/psychological disorder or any other reason that the subject is expected to have difficulty complying with the study requirements or understanding the participants With the objectives and potential risks of the study;
19. To the knowledge of the investigator, subjects were unlikely to follow up or were not expected to complete 1 year of follow-up;
20. Life expectancy is less than 1 year;

22. Refusal to participate in the study

Primary outcomes:
measure: Major adverse cardiovascular and cerebrovascular event (MACCE)
timeFrame: 12 months after randomization
measure: BARC type 3 or 5 bleeding
timeFrame: 12 months after randomization
Secondary outcomes:
measure: Net adverse clinical event (NACE)
timeFrame: 12 months after randomization
measure: Cardiovascular death or myocardial infarction
timeFrame: 12 months after randomization
measure: All-cause death or myocardial infarction
timeFrame: 12 months after randomization
measure: Stent thrombosis
timeFrame: 12 months after randomization
measure: Any myocardial infarction
timeFrame: 12 months after randomization
measure: Target vessel myocardial infarction
timeFrame: 12 months after randomization
measure: Stroke
timeFrame: 12 months after randomization
measure: Ischemic stroke
timeFrame: 12 months after randomization
measure: Hemorrhagic stroke
timeFrame: 12 months after randomization
measure: Cardiovascular death
timeFrame: 12 months after randomization
measure: All-cause death
timeFrame: 12 months after randomization
measure: Repeat revascularization
timeFrame: 12 months after randomization
measure: Target vessel revascularization
timeFrame: 12 months after randomization
measure: BARC type 2, 3 or 5 bleeding
timeFrame: 12 months after randomization
measure: Any bleeding
timeFrame: 12 months after randomization
Other outcomes:
Locations:
city: Beijing
country: China
facility: Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College
state: Beijing
Study officials:
affiliation: Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
name: Kefei Dou, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
name: Kongyong Cui, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: