Drug-Coated Balloon vs. Drug-Eluting Stent for Clinical Outcomes in Patients With Large Coronary Artery Disease (REVERSE)

Randomised Trial of Drug-Coated Balloon Versus Drug-Eluting Stent for Clinical Outcomes in Patients With Large Coronary Artery Disease

Prospective, randomised, open-label, international multicenter trial to evaluate the safety and efficacy of drug-coated balloon (DCB) treatment compared to drug-eluting stenting (DES) in patients with large coronary artery disease.

Study Overview

• Status: Recruiting
• Conditions: Myocardial Ischemia; Coronary Artery Disease; Acute Coronary Syndrome; Coronary Stenosis; De Novo Stenosis
• Intervention / Treatment: Device: SeQuent® Please NEO drug-coated balloon catheter; Device: Current-generation drug-eluting stent

Detailed Description

Although several reports suggested that DCB application was safe for larger coronary artery lesions and showed good long-term outcomes, there is limited randomised controlled trial (RCT) data on the safety and efficacy of DCB in large coronary artery disease.

Therefore, the study aims to demonstrate the non-inferiority of the drug-coated balloon (DCB) treatment against current-generation drug-eluting stenting (DES) in patients with de novo lesions in large coronary artery disease (reference vessel diameter ≥3.0 mm by visual estimation).

The hypothesis of the study is the clinical outcomes of patients treated with DCB are non-inferior to those treated with current-generation DES.

• Study Type: Interventional
• Enrollment (Estimated): 1436
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Hooi Sian Eng, Ph.D; Phone Number: +60-12-428-2880; Email: hooi.eng@bbraun.com
• Study Contact Backup: Name: Philip Steen, MD; Phone Number: +49-30-568207-124; Email: philip.steen@bbraun.com

Study Locations

• Korea, Republic of
  • Daegu, Korea, Republic of, 42601
    • Recruiting
    • Keimyung University Dongsan Hospital
    • Contact: Chang-Wook Nam, MD, Ph.D
    • Principal Investigator: Chang-Wook Nam, MD, Ph.D
  • Seoul, Korea, Republic of, 13631
    • Recruiting
    • Kangbuk Samsung Hospital
    • Contact: Jong-Young Lee, MD, Ph.D
    • Principal Investigator: Jong-Young Lee, MD, Ph.D
  • Gangwon-do
    • Chuncheon, Gangwon-do, Korea, Republic of, 24289
      • Recruiting
      • Kangwon National University Hospital
      • Contact: Ae-Young Her, MD, Ph.D
      • Principal Investigator: Ae-Young Her, MD, Ph.D
  • Gyeonggi-do
    • Ansan-si, Gyeonggi-do, Korea, Republic of, 15355
      • Recruiting
      • Korea University Ansan Hospital
      • Contact: Sunwon Kim, MD, Ph.D
      • Principal Investigator: Sunwon Kim, MD, Ph.D
    • Goyang-si, Gyeonggi-do, Korea, Republic of, 10380
      • Not yet recruiting
      • Inje University Ilsan Paik Hospital
      • Contact: Joon-Hyung Doh, MD, Ph.D
      • Principal Investigator: Joon-Hyung Doh, MD, Ph.D
  • Gyeongsangnam-do
    • Changwon, Gyeongsangnam-do, Korea, Republic of, 51472
      • Recruiting
      • Gyeongsang National University Changwon Hospital
      • Contact: Yongwhi Park, MD, Ph.D
      • Principal Investigator: Yongwhi Park, MD, Ph.D
  • Ulsan
    • Donggu, Ulsan, Korea, Republic of, 44033
      • Recruiting
      • Ulsan University Hospital
      • Principal Investigator: Eun-Seok Shin, MD, Ph.D
      • Contact: Eun-Seok Shin, MD, Ph.D; Phone Number: +82-10-6319-4025; Email: sesim1989@gmail.com
• Malaysia
  • Kuala Lumpur, Malaysia, 59100
    • Recruiting
    • University Malaya Medical Centre
    • Contact: Ahmad Syadi Mahmood Zuhdi, MD, Ph.D
    • Principal Investigator: Ahmad Syadi Mahmood Zuhdi, MD, Ph.D
  • Kuala Lumpur, Malaysia, 50400
    • Recruiting
    • National Heart Institute Malaysia
    • Contact: Shaiful Azmi Yahaya, MD
    • Principal Investigator: Shaiful Azmi Yahaya, MD
  • Kuala Lumpur, Malaysia, 50470
    • Recruiting
    • Cardiac Vascular Sentral Kuala Lumpur
    • Principal Investigator: Rosli Mohd Ali, MD
    • Contact: Rosli Mohd Ali, MD
  • Sabah
    • Kota Kinabalu, Sabah, Malaysia, 88300
      • Recruiting
      • Queen Elizabeth II Hospital
      • Contact: Houng Bang Liew, MD
      • Principal Investigator: Houng Bang Liew, MD
  • Sarawak
    • Kuching, Sarawak, Malaysia, 94300
      • Recruiting
      • Sarawak Heart Center
      • Contact: Tiong Kiam Ong, MD
      • Principal Investigator: Tiong Kiam Ong, MD
  • Selangor
    • Kajang, Selangor, Malaysia, 43000
      • Recruiting
      • Sultan Idris Shah Serdang Hospital
      • Contact: Kamaraj Selvaraj, MD
      • Principal Investigator: Kamaraj Selvaraj, MD
• Singapore
  • Novena, Singapore, 308433
    • Not yet recruiting
    • Tan Tock Seng Hospital
    • Contact: Hee Hwa Ho, MD
    • Principal Investigator: Hee Hwa Ho, MD
• Taiwan
  • Taoyuan, Taiwan, 33305
    • Not yet recruiting
    • Chang Gung Memorial Hospital
    • Contact: I-Chang Hsieh, MD, Ph.D
    • Principal Investigator: I-Chang Hsieh, MD, Ph.D

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patient-related:

  1. Patient must be ≥ 18 years of age
  2. Patient is able to verbally confirm understanding of the study aim, risks, benefits, and treatment alternatives of receiving DCB or DES and he/she or his/her legally authorized representative provides written informed consent prior to any study-related procedure
  3. (i) Clinical evidence of angina, and/or (ii) an abnormal functional study demonstrating myocardial ischemia due to the target lesion(s), or (iii) acute coronary syndrome [unstable angina or non-ST-elevation myocardial infarction (NSTEMI) or uneventful STEMI (≥ 48 hours after primary PCI and no sign of thrombus in lesion(s) to treat)]
  4. Patient with lesions suitable for PCI with a DCB (and/or DES) according to the Instructions for Use
  5. Patient is able to comply with the study protocol and agrees to undergo the clinical follow-up of 30 days, 6 months, 12 months, 24 months, and 36 months

• Lesion-related:

  1. Presence of significant de novo large vessel coronary artery disease (reference vessel diameter ≥3.0 mm by visual estimation) with either ≥ 70% diameter stenosis or intermediate ≥ 50% to <70% diameter stenosis with abnormal functional test or symptom of ischemia
  2. Successful lesion preparation. For randomisation, the lesion must satisfy the following criteria after optimal balloon angioplasty: no flow-limiting dissection (TIMI=3), and residual stenosis is ≤ 30%
• Multivessel disease with two or more vessels showing diameter stenosis of 50% or more is not an exclusion as long as it fulfills all study's eligibility criteria.
• In diffuse lesion, inclusion is possible if the proximal reference vessel diameter is 3.0 mm or more.

Exclusion Criteria:

• Patient-related:

  1. Intolerance or allergy to Paclitaxel and/or the delivery matrix (main ingredient: Iopromide)
  2. Severe allergy to contrast media
  3. Recent STEMI (ongoing or < 48 hours after primary PCI and/or has sign of thrombus in lesion(s) to treat)
  4. NSTEMI hemodynamically unstable
  5. Known left ventricular ejection fraction of <30%
  6. Inability to take dual antiplatelet therapy or anticoagulation, or single antiplatelet therapy for at least six months
  7. Non-cardiac co-morbid conditions that may result in protocol non-compliance and inability of patient to complete the study (per the site investigator's medical judgment)
  8. Patient with concomitant medical illnesses that require cytostatic, radiation therapy or renal replacement therapy
  9. Patient who is currently/ planning to participate in another clinical trial when such participation could confound the treatment or outcomes of this study, except for observational registry
  10. Pregnancy or lactation
  11. Patient under administrative or judicial custody

• Lesion-related:

  1. Small vessel disease, defined as <3.0 mm of reference vessel diameter by visual estimation
  2. In-stent restenosis lesions for study lesions

  3. Patient will be excluded if meet any of the following angiographic exclusion criteria after lesion preparation:

     (i) Flow limiting dissection with TIMI flow < III (ii) Residual diameter stenosis >30%

     * The case of persistent ischemic symptoms/signs is up to the operator's decision

  4. Lesions which are untreatable with PCI or other interventional techniques and coronary artery spasm in the absence of a significant stenosis
  5. Left main disease or aorta-ostial lesion requiring revascularization
  6. Severely calcified or tortuous vessels precluding DCB or DES application
  7. Prior Coronary Artery Bypass Graft (CABG)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SeQuent® Please NEO drug-coated balloon catheter	Device: SeQuent® Please NEO drug-coated balloon catheter; Treatment of coronary artery disease with SeQuent® Please NEO for de novo lesions in native large coronary arteries
Experimental: Current-generation drug-eluting stent	Device: Current-generation drug-eluting stent; Treatment of coronary artery disease with current-generation drug-eluting stent for de novo lesions in native large coronary arteries

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Net Adverse Clinical Event (NACE)	Net adverse clinical event (NACE): a composite of all-cause death, non-fatal myocardial infarction, clinically driven target vessel revascularization, or major bleeding (BARC type 3 to 5)	At 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause death		At 12, 24, and 36 months
Non-fatal myocardial infarction		At 12, 24, and 36 months
Clinically driven target vessel revascularization		At 12, 24, and 36 months
Major bleeding (BARC type 3 to 5)		At 12, 24, and 36 months
Cardiac death		At 12, 24, and 36 months
Target vessel myocardial infarction		At 12, 24, and 36 months
Periprocedural myocardial infarction		At 12, 24, and 36 months
Target lesion revascularization		At 12, 24, and 36 months
Stent/lesion thrombosis in treated lesion defined according to the Academic Research Consortium-2 (ARC-2) criteria		At 12, 24, and 36 months
Rehospitalization related to study endpoints	Rate of hospitalization related to study endpoints	At 30 days, 12 months, 24 months, and 36 months
Stroke (ischemic and hemorrhagic)	Number of participants with stroke (ischemic and hemorrhagic)	At 12, 24, and 36 months
Total angioplasty procedure time		During the index procedure
Fluoroscopy time of the angioplasty procedure		During the index procedure
Contrast volume of the angioplasty procedure		During the index procedure
Number of devices (DCB/ DES) used for PCI treatment		During the index procedure

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Late lumen loss (LLL)	LLL is defined as: the minimal lumen diameter (MLD) immediately after PCI minus the MLD at the follow-up.	At 9-12 months post-procedure
Percentage of diameter stenosis		At 9-12 months post-procedure
Minimal lumen diameter		At 9-12 months post-procedure
Binary restenosis		At 9-12 months post-procedure
Quality of life analysis	Quality of life analysis using EQ-5D-5L questionnaire	After 12, 24, and 36 months
Incidence of angina		At baseline and 12 months
Dual Antiplatelet Therapy (DAPT) duration		At 30 days, 6 months, and 12 months
Comparison of NACE between DCB vs. DES in sex difference, diabetes mellitus, and multivessel disease patients		At 1 year

Collaborators and Investigators

• Sponsor: B. Braun Medical Industries Sdn. Bhd.
• Collaborators: Seoul National University Hospital; Ulsan University Hospital; European Cardiovascular Research Center; B. Braun Melsungen AG; Universität des Saarlandes
• Investigators: Study Chair: Eun-Seok Shin, MD, Ph.D, Ulsan University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 7, 2023
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): September 1, 2028

Study Registration Dates

• First Submitted: April 11, 2023
• First Submitted That Met QC Criteria: April 26, 2023
• First Posted (Actual): May 6, 2023

Study Record Updates

• Last Update Posted (Estimated): November 17, 2023
• Last Update Submitted That Met QC Criteria: November 16, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: percutaneous coronary intervention; coronary artery disease; cardiovascular disease; angina; acute coronary syndrome; drug-coated balloon; drug-eluting stent; ischemia; stenosis; angioplasty; heart disease; de novo; randomised trial; coronary occlusion; large vessel; SeQuent Please
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Pathological Conditions, Anatomical; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Ischemia; Constriction, Pathologic; Acute Coronary Syndrome; Coronary Stenosis
• Other Study ID Numbers: AAG-G-H-2124

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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