DAPT-Lp(a): 24 Versus 12-Month Dual Antiplatelet Therapy After Drug-Eluting Stent in Patients With Elevated Lipoprotein(a) Levels

• Sponsor: China National Center for Cardiovascular Diseases (Other)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT06014060
• Collaborator: (none)
• Enrollment: 3,300
• Location: 1
• Arms: 2
• Anticipated Duration (Months): 60
• Patients Per Site Per Month: 55

Study Details

Study Description

Brief Summary

The purpose of this study is (1) to determine whether 24-month dual antiplatelet therapy (DAPT) is superior to 12-month DAPT after percutaneous coronary intervention (PCI) with drug-eluting stent (DES) with respect to major adverse cardiovascular and cerebrovascular events (all-cause death, myocardial infarction, or stroke) in patients with elevated lipoprotein(a)[Lp(a)] levels (>30mg/dL); (2) to determine whether 24-month DAPT is non-inferior to 12-month DAPT after PCI with DES with respect to net adverse clinical events (all-cause death, myocardial infarction, stroke or Bleeding Academic Research Consortium [BARC] type 3 or 5 bleeding) in patients with elevated Lp(a) levels (>30mg/dL).

Condition or Disease	Intervention/Treatment	Phase
Elevated Lipoprotein(a) Level; Coronary Artery Disease; Drug-Eluting Stent; Dual Antiplatelet Therapy	Procedure: 24 Months DAPT; Procedure: 12 Months DAPT	N/A

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.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 3300 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Masking Description: Participants and study investigators were aware of the study-group assignments, but outcome adjudicators were not. All potential events were adjudicated according to prespecified criteria by an independent clinical events committee whose members were unaware of the trial-group assignments.
• Primary Purpose: Treatment
• Official Title: 24-Month Versus 12-Month Dual Antiplatelet Therapy After Drug-Eluting Stent in Patients With Elevated Lipoprotein(a) Levels
• Anticipated Study Start Date: Jan 1, 2024
• Anticipated Primary Completion Date: Dec 31, 2028
• Anticipated Study Completion Date: Dec 31, 2028

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 24 Months DAPT Dual antiplatelet therapy consisting of aspirin and clopidogrel will be continued for 12 months after randomisation.	Procedure: 24 Months DAPT; All subjects will receive co-administration of aspirin (100 mg/day) and clopidogrel (75 mg/day) for 12 months after randomization.
Active Comparator: 12 Months DAPT Dual antiplatelet therapy will be discontinued and patients will receive aspirin monotherapy for 12 months after randomisation.	Procedure: 12 Months DAPT; All subjects will receive aspirin (100 mg/day) monotherapy without co-administration of clopidogrel for 12 months after randomization.

Outcome Measures

Primary Outcome Measures

1. Major adverse cardiovascular and cerebrovascular event (MACCE) [12 months after randomization]

   The primary endpoint was major adverse cardiovascular and cerebrovascular event (MACCE), defined as a composite of all-cause death, myocardial infarction or stroke.

Secondary Outcome Measures

1. Net adverse clinical event (NACE) [12 months after randomization]

   The key secondary endpoint was net adverse clinical event, defined as a composite of all-cause death, myocardial infarction, stroke or Bleeding Academic Research Consortium (BARC)] type 3 or 5 bleeding.

2. Cardiovascular death or myocardial infarction [12 months after randomization]

   Number of patients with a first occurrence of adjudicated composite of cardiovascular death or myocardial infarction.

3. All-cause death or myocardial infarction [12 months after randomization]

   Number of patients with a first occurrence of adjudicated composite of all-cause death or myocardial infarction.

4. All-cause death [12 months after randomization]

   Number of patients with the occurrence of adjudicated all-cause death.

5. Cardiovascular death [12 months after randomization]

   Number of patients with the occurrence of adjudicated cardiovascular death.

6. Any myocardial infarction [12 months after randomization]

   Number of patients with a first occurrence of adjudicated any myocardial infarction.

7. Target vessel myocardial infarction [12 months after randomization]

   Number of patients with a first occurrence of adjudicated target vessel myocardial infarction.

8. Stroke [12 months after randomization]

   Number of patients with a first occurrence of adjudicated stroke.

9. Ischemic stroke [12 months after randomization]

   Number of patients with a first occurrence of adjudicated ischemic stroke.

10. Hemorrhagic stroke [12 months after randomization]

    Number of patients with a first occurrence of adjudicated hemorrhagic stroke.

11. Definite/probable stent thrombosis [12 months after randomization]

    Number of patients with a first occurrence of adjudicated definite/probable stent thrombosis.

12. Repeat revascularization [12 months after randomization]

    Number of patients with a first occurrence of adjudicated repeat revascularization.

13. Target vessel revascularization [12 months after randomization]

    Number of patients with a first occurrence of adjudicated target vessel revascularization.

14. Any bleeding [12 months after randomization]

    Number of patients with a first occurrence of adjudicated any bleeding.

15. BARC type 2, 3 or 5 bleeding [12 months after randomization]

    Number of patients with a first occurrence of adjudicated BARC type 2, 3 or 5 bleeding.

16. BARC type 3 or 5 bleeding [12 months after randomization]

    Number of patients with a first occurrence of adjudicated BARC type 3 or 5 bleeding.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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. Subjects who are event-free at 1 year after PCI with drug-eluting stent (DES);

4. Subjects (or legal guardian) understand the trial requirements and the treatment procedures and provides written informed;

5. Subjects are willing to comply with all protocol-required follow-up evaluation.

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. Subjects who have other diseases requiring dual antiplatelet therapy (DAPT) such as peripheral vascular disease;

4. Subjects who cannot tolerate DAPT therapy or receive anticoagulation therapy at the time of randomization;

5. Planned surgery necessitating discontinuation of antiplatelet therapy (>14 days) within the 12 months after randomization;

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. Unstable or severe pulmonary edema/decompensated congestive heart failure;

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. Recurrent symptoms of ischemia;

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. History or clinical evidence of active liver disease or hepatic dysfunction, defined as alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3 × upper limit of normal (ULN), or total bilirubin > 2 × ULN; Unexplained elevated creatine kinase (CK) concentration >5 × ULN or elevation due to known muscle disease;

13. Severe acute or chronic infectious disease;

14. History of severe rheumatic immune disease or malignant tumor;

15. 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);

16. Drug or alcohol abuse, and inability/unwillingness to abstain from drug abuse and excessive alcohol consumption during the study;

17. Recipient of any major organ transplant (eg, lung, liver, heart, bone marrow, renal);

18. Subject likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures (eg, Clinical Outcome Assessments) to the best of the subject and investigator's knowledge;

19. Any uncontrolled or serious disease, or any medical or surgical condition (such as known active infection or major hematologic, renal, metabolic, gastrointestinal or endocrine dysfunction, or a chronic disease or infection [eg, HIV]), that may either interfere with participation in the clinical study and is not currently stable and appropriately managed in the judgment of the investigator, and/or put the subject at significant risk (according to investigator's judgment) if he/she participates in the clinical study;

20. Mental/psychological impairment/neurocognitive disorder, or any other reason to expect patient difficulty in complying with the requirements of the study or understanding the goal and potential risks of participating in the study;

21. Concurrent medical condition with a life expectancy of < 1 year;

22. Subject unable to give informed consent;

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College	Beijing	Beijing	China	100037

Sponsors and Collaborators

• China National Center for Cardiovascular Diseases

Investigators

• Principal Investigator: Kefei Dou, MD, PhD, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
• Principal Investigator: Kongyong Cui, MD, PhD, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Kefei Dou, MD, Professor, China National Center for Cardiovascular Diseases
• ClinicalTrials.gov Identifier: NCT06014060
• Other Study ID Numbers: Lipoprotein(a) and prognosis
• First Posted: Aug 28, 2023
• Last Update Posted: Aug 29, 2023
• Last Verified: Aug 1, 2023

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Kefei Dou, MD, Professor, China National Center for Cardiovascular Diseases: Lipoprotein(a); Coronary Artery Disease; Drug-Eluting Stent; Percutaneous Coronary Intervention; Dual Antiplatelet Therapy
• Additional relevant MeSH terms: Coronary Artery Disease; Myocardial Ischemia; Coronary Disease

Study Results

No Results Posted as of Aug 29, 2023