Preventive Drug-coated Balloon Angioplasty in Vulnerable Atherosclerotic Plaque (RESTORE Trial)

A Multicenter, Prospective, Open-label, Controlled, Randomized Trial of Preventive Drug-coated Balloon Angioplasty in Vulnerable Atherosclerotic Plaque (RESTORE Trial)

The objective of this multicenter, prospective, open-label, controlled, randomized trial is to demonstrate the superiority of drug-coated balloon (DCB) treatment on non-flow limited vulnerable plaque as compared to guideline-directed medical therapy (GDMT) in improving clinical cardiovascular outcomes in patients with acute coronary syndrome.

Study Overview

• Status: Recruiting
• Conditions: Acute Coronary Syndrome (ACS)
• Intervention / Treatment: Device: Drug-coated balloon; Drug: Guideline-directed medical treatment

• Study Type: Interventional
• Enrollment (Estimated): 1860
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Haibo Jia, PhD; Phone Number: 15945685291; Email: jhb101180@163.com

Study Locations

• China
  • Beijing
    • Beijin, Beijing, China, 101149
      • Not yet recruiting
      • Affiliated Beijing Luhe Hospital of Capital Medical University
      • Contact: Guangyao Zhai
      • Principal Investigator: Guangyao zhai
  • Guizhou
    • Zunyi, Guizhou, China, 563000
      • Not yet recruiting
      • Affiliated Hospital of Zunyi Medical University
      • Contact: Ranzun Zhao
      • Principal Investigator: Ranzun Zhao
  • Heilongjiang
    • Daqing, Heilongjiang, China, 150000
      • Not yet recruiting
      • Daqing Oilfield General Hospital
      • Contact: Zhiqi Sun
      • Principal Investigator: Zhiqi Sun
    • Harbin, Heilongjiang, China, 150000
      • Recruiting
      • The Second Affiliated Hospital of Harbin Medical University
      • Contact: Haibo Jia, PhD
      • Principal Investigator: Bo Yu, PhD
      • Sub-Investigator: Haibo Jia, PhD
    • Jiamusi, Heilongjiang, China, 150000
      • Not yet recruiting
      • The First Affiliated Hospital of Jiamusi University
      • Contact: Guangyuan Yang
      • Principal Investigator: Guangyuan Yang
    • Mudanjiang, Heilongjiang, China, 150000
      • Not yet recruiting
      • Mudanjiang Cardiovascular Hospital
      • Contact: Kai Liu
      • Principal Investigator: Kai Liu
  • Henan
    • Zhengzhou, Henan, China, 450000
      • Not yet recruiting
      • The First Affiliated Hospital of Zhengzhou University
      • Contact: Chunguang Qiu
      • Principal Investigator: Chunguang Qiu
    • Zhengzhou, Henan, China, 450000
      • Not yet recruiting
      • Fuwai Central China Cardiovascular Hospital
      • Contact: Xiaohui Zheng
      • Principal Investigator: Xiaohui Zheng
  • Hubei
    • Wuhan, Hubei, China, 430022
      • Not yet recruiting
      • Tongji Hospital Tongji Medical College of HUST
      • Contact: Xiang Chen
      • Principal Investigator: Xiang Chen
  • Jilin
    • Changchun, Jilin, China, 132000
      • Not yet recruiting
      • The Third Second Hospital of Jilin University
      • Contact: Bin Liu
      • Principal Investigator: Bin Liu
  • Liaoning
    • Dalian, Liaoning, China, 116000
      • Not yet recruiting
      • The First Affiliated Hospital of Dalian Medical University
      • Contact: Bo Zhang
      • Principal Investigator: Bo Zhang
    • Dalian, Liaoning, China, 116000
      • Not yet recruiting
      • Dalian Municipal Central Hospital
      • Contact: Xiaoqun Zheng
      • Principal Investigator: Xiaoqun Zheng
    • Shengyang, Liaoning, China, 132000
      • Not yet recruiting
      • The People's Hospital of Liaoning Province
      • Contact: Bo Luan
      • Principal Investigator: Bo Luan
  • Neimenggu
    • Hohhot, Neimenggu, China, 011500
      • Not yet recruiting
      • The Affiliated Hospital of Neimenggu Medical University
      • Contact: Fengying Chen
      • Principal Investigator: Fengying Chen
  • Shandong
    • Jinan, Shandong, China, 250000
      • Not yet recruiting
      • Shandong Provincial Hospital
      • Contact: Haitao Yuan
      • Principal Investigator: Haitao Yuan
    • Jining, Shandong, China, 250000
      • Not yet recruiting
      • Affiliated Hospital of Jining Medical University
      • Contact: Lijun Gan
      • Principal Investigator: Lijun Gan
    • Qingdao, Shandong, China, 250000
      • Not yet recruiting
      • The Affiliated Hospital of Qingdao University
      • Contact: Peng Li
      • Principal Investigator: Peng Li
    • Yantai, Shandong, China, 250000
      • Not yet recruiting
      • Yantai Yuhuangding Hospital
      • Contact: Lin Zhong
      • Principal Investigator: Lin Zhong

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Subjects must be between 18 and 80 years of age
2. Subject must present with acute myocardial infarction or unstable angina planned for PCI
3. Successful stent implantation (i.e., residual stenosis less than 20%) must be done in culprit lesions and any lesions with ischemia evidence (e.g., QFR equal or less than 0.8)
4. Subject must have at least one native non-culprit lesion with visually estimated stenosis of 40-80% and QFR >0.8
5. Target lesion must have a visually estimated diameter of 2.0-4.0 mm and length of ≤ 50 mm
6. Target lesion must have any two of the intravascular imaging criteria of PB >65%, MLA <3.5 mm^2 (OCT) or 4.0mm^2 (IVUS), FCT <75 μm, or maximal lipid arc >180°
7. Subject must provide written informed consent before any study-related procedure

Exclusion Criteria:

1. Subject has known hypersensitivity or contraindication to any of the study drugs (including all asprin, P2Y12 inhibitors, one or more components of the study devices, including paclitaxel, etc) that cannot be adequately pre-medicated
2. Subject is receiving immunosuppressant therapy or has known immunosuppressive or severe autoimmune disease that requires chronic immunosuppressive therapy (e.g., human immunodeficiency virus, systemic lupus erythematosus, etc.)
3. Hypotension, shock, or need for mechanical support or intravenous vasopressors;
4. Creatinine clearance ≤30 ml/min/1.73 m^2 (as calculated by MDRD formula for estimated GFR)
5. Left ventricular ejection fraction<30% by the most recent imaging test within 30 days before procedure (echo, MRI, contrast left ventriculography or others)
6. Life expectancy <2 years for any
7. Subject is currently participating in another investigational drug or device clinical study that has not yet completed its primary endpoint
8. Presence of other anatomic or comorbid conditions, or other medical, social, or psychological conditions that, in the investigator's opinion, could limit the subject's ability to participate in the clinical investigation or to comply with follow-up requirements, or impact the scientific soundness of the clinical investigation results.
9. The target lesion is located within 10 mm of the proximal or distal of stent
10. The target lesion cannot be in the left main coronary artery
11. The target lesion is located in a bifurcation lesion (i.e., the diameter of the branch vessels is >2 mm with >50% of stenosis)
12. The target lesion is located in severe calcification or tortuosity of vessels
13. The target lesion involved in the ostium of LAD, LCX or RCA (within 3 mm of the ostium)
14. The target lesion is located within the bypass graft artery

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DCB treatment; Non-flow limited vulnerable plaque will be treated by drug-coated balloon when the enrolled individual is randomized into DCB treatment group. The individual located in DCB treatment will receive guideline-directed medical treatment.	Device: Drug-coated balloon; Non-culprit lesion will be pretreated before DCB treatment. The bail-out stent treatment is permitted if pretreatment failed.; Drug: Guideline-directed medical treatment; All individuals will receive guideline-directed medical treatment.
Active Comparator: Guideline-directed medical treatment; Non-flow limited vulnerable plaque will be left with no intervention when the individual is randomized into guideline-directed medical treatment group. The individual will receive guideline-directed medical treatment alone.	Drug: Guideline-directed medical treatment; All individuals will receive guideline-directed medical treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Target lesion failure (TLF)	At 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Target lesion failure (TLF)		At 30 days
Target lesion failure (TLF)		At 6 months
Target lesion failure (TLF)		At 12 months
Major cardiac adverse event (MACE)	MACE is defined as the composite of all-cause death, recurrent myocardial infarction, revascularization, unplanned readmission for angina exacerbation or unstable angina	At 30 days
Major cardiac adverse event (MACE)	MACE is defined as the composite of all-cause death, recurrent myocardial infarction, revascularization, unplanned readmission for angina exacerbation or unstable angina	At 6 months
Major cardiac adverse event (MACE)	MACE is defined as the composite of all-cause death, recurrent myocardial infarction, revascularization, unplanned readmission for angina exacerbation or unstable angina	At 12 months
Major cardiac adverse event (MACE)	MACE is defined as the composite of all-cause death, recurrent myocardial infarction, revascularization, unplanned readmission for angina exacerbation or unstable angina	At 24 months
All-cause death	Any death will be recorded as all-cause death	At 30 days
All-cause death	Any death will be recorded as all-cause death	At 6 months
All-cause death	Any death will be recorded as all-cause death	At 12 months
All-cause death	Any death will be recorded as all-cause death	At 24 months
Cardiac death and target lesion MI	All deaths are considered cardiac unless an unequivocal non-cardiac cause can be established. Cardiac death is defined as any death due to proximate cardiac cause (e.g. MI, low-output failure, fatal arrhythmia), witnessed death and death of unknown cause, all procedure related deaths including those related to concomitant treatment	At 30 days
Cardiac death and target lesion MI	All deaths are considered cardiac unless an unequivocal non-cardiac cause can be established. Cardiac death is defined as any death due to proximate cardiac cause (e.g. MI, low-output failure, fatal arrhythmia), witnessed death and death of unknown cause, all procedure related deaths including those related to concomitant treatment	At 6 months
Cardiac death and target lesion MI	All deaths are considered cardiac unless an unequivocal non-cardiac cause can be established. Cardiac death is defined as any death due to proximate cardiac cause (e.g. MI, low-output failure, fatal arrhythmia), witnessed death and death of unknown cause, all procedure related deaths including those related to concomitant treatment	At 12 months
Cardiac death and target lesion MI	All deaths are considered cardiac unless an unequivocal non-cardiac cause can be established. Cardiac death is defined as any death due to proximate cardiac cause (e.g. MI, low-output failure, fatal arrhythmia), witnessed death and death of unknown cause, all procedure related deaths including those related to concomitant treatment	At 24 months
Cardiac death	All deaths are considered cardiac unless an unequivocal non-cardiac cause can be established. Cardiac death is defined as any death due to proximate cardiac cause (e.g. MI, low-output failure, fatal arrhythmia), witnessed death and death of unknown cause, all procedure related deaths including those related to concomitant treatment	At 30 days
Cardiac death	All deaths are considered cardiac unless an unequivocal non-cardiac cause can be established. Cardiac death is defined as any death due to proximate cardiac cause (e.g. MI, low-output failure, fatal arrhythmia), witnessed death and death of unknown cause, all procedure related deaths including those related to concomitant treatment	At 6 months
Cardiac death	All deaths are considered cardiac unless an unequivocal non-cardiac cause can be established. Cardiac death is defined as any death due to proximate cardiac cause (e.g. MI, low-output failure, fatal arrhythmia), witnessed death and death of unknown cause, all procedure related deaths including those related to concomitant treatment	At 12 months
Cardiac death	All deaths are considered cardiac unless an unequivocal non-cardiac cause can be established. Cardiac death is defined as any death due to proximate cardiac cause (e.g. MI, low-output failure, fatal arrhythmia), witnessed death and death of unknown cause, all procedure related deaths including those related to concomitant treatment	At 24 months
Target lesion myocardial infarction	Target lesion Myocardial Infarction (TL-MI) and non-TL-MI will be assessed	At 30 days
Target lesion myocardial infarction	Target lesion Myocardial Infarction (TL-MI) and non-TL-MI will be assessed	At 6 months
Target lesion myocardial infarction	Target lesion Myocardial Infarction (TL-MI) and non-TL-MI will be assessed	At 12 months
Target lesion myocardial infarction	Target lesion Myocardial Infarction (TL-MI) and non-TL-MI will be assessed	At 24 months
Periprocedural myocardial infarction	Periprocedural Myocardial Infarction (TL-MI) and non-Periprocedural will be assessed.	At 30 days
Periprocedural myocardial infarction	Periprocedural Myocardial Infarction (TL-MI) and non-Periprocedural will be assessed.	At 6 months
Periprocedural myocardial infarction	Periprocedural Myocardial Infarction (TL-MI) and non-Periprocedural will be assessed.	At 12 months
Periprocedural myocardial infarction	Periprocedural Myocardial Infarction (TL-MI) and non-Periprocedural will be assessed.	At 24 months
Periprocedural and non-periprocedural myocardial infarction	Periprocedural Myocardial Infarction (TL-MI) and non-periprocedural will be assessed	At 30 days
Periprocedural and non-periprocedural myocardial infarction	Periprocedural Myocardial Infarction (TL-MI) and non-periprocedural will be assessed	At 6 months
Periprocedural and non-periprocedural myocardial infarction	Periprocedural Myocardial Infarction (TL-MI) and non-periprocedural will be assessed	At 12 months
Periprocedural and non-periprocedural myocardial infarction	Periprocedural Myocardial Infarction (TL-MI) and non-periprocedural will be assessed	At 24 months
Target vessel failure (TVF)	TVF is defined as the composite of cardiac death, target vessel myocardial infarction and ischemia-driven target vessel revascularization.	At 30 days
Target vessel failure (TVF)	TVF is defined as the composite of cardiac death, target vessel myocardial infarction and ischemia-driven target vessel revascularization.	At 6 months
Target vessel failure (TVF)	TVF is defined as the composite of cardiac death, target vessel myocardial infarction and ischemia-driven target vessel revascularization.	At 12 months
Target vessel failure (TVF)	TVF is defined as the composite of cardiac death, target vessel myocardial infarction and ischemia-driven target vessel revascularization.	At 24 months
Minimal lumen area after DCB treatment	Post-procedure imaging examination is required	At baseline
Plaque burden after DCB treatment	Post-procedure imaging examination is required	At baseline
FCT after DCB treatment	Post-procedure imaging examination is required	At baseline
Lipid arc after DCB treatment	Post-procedure imaging examination is required	At baseline
FCT <75 μm after DCB treatment	Post-procedure imaging examination is required	At baseline
PB >65% after DCB treatment	Post-procedure imaging examination is required	At baseline
PB >70% after DCB treatment	Post-procedure imaging examination is required	At baseline
MLA <3.5 mm^2 after DCB treatment	Post-procedure imaging examination is required	At baseline
Maximal lipid arc >180° after DCB treatment	Post-procedure imaging examination is required	At baseline
Cardiac biomarkers: GDF-15, interleukin-6, interleukin-1β and ceramide etc.	The centers with sample preservation qualifications will be asked to preserve blood samples.	At baseline and one-year follow-up

Collaborators and Investigators

• Sponsor: Harbin Medical University
• Collaborators: Shanghai Shenqi Medical Technology Co., Ltd
• Investigators: Principal Investigator: Bo Yu, PhD, The Second Affiliated Hospital of Harbin Medical University

Study record dates

Study Major Dates

• Study Start (Actual): April 16, 2024
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2030

Study Registration Dates

• First Submitted: April 10, 2024
• First Submitted That Met QC Criteria: April 10, 2024
• First Posted (Actual): April 15, 2024

Study Record Updates

• Last Update Posted (Actual): May 22, 2024
• Last Update Submitted That Met QC Criteria: May 21, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Pathological Conditions, Anatomical; Acute Coronary Syndrome; Plaque, Atherosclerotic
• Other Study ID Numbers: KY2023-156

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No