Comparison of Biomatrix and Orsiro Drug Eluting Stent (BIODEGRADE)

Comparison of Biomatrix and Orsiro Drug Eluting Stent in Angiographic Result in Patients With All-comer Patients With Coronary Artery Disease : A Multicenter, Randomized, Open Label Study (BIODEGRADE Study)

The primary objective of the BIODEGRADE study is to evaluate clinical efficacy of the Orsiro drug-eluting stent compared with Biomatrix drug-eluting stent, both of which have biodegradable polymer for the treatment of all-comers' coronary artery diseases.

Study Overview

• Status: Completed
• Conditions: Myocardial Ischemia; Coronary Artery Disease
• Intervention / Treatment: Device: Orsiro drug eluting stent; Drug: Biomatrix drug eluting stent

Detailed Description

The rate of in-stent restenosis after percutaneous coronary intervention (PCI) has decreased since the launching of drug-eluting stents (DES). However, restenosis still remains a problem since PCI is being performed on more complex, calcified, tortuous and tough lesions. Furthermore, there is still a controversy on whether these DES are more thrombogenic than bare metal stent (BMS) because of inflammation related to the polymer coating and delayed vessel healing due to the eluted drug despite of reduced restenosis. Therefore, works aiming to reduce both restenosis and thrombotic event are still on-going in the field of interventional cardiology, and there has been a rush of various third generation DES with "biodegradable polymer". Recently, Orsiro hybrid DES (Biotronik AG, Bulach, Switzeland) has been developed. The Orsiro DES incorporated optimally combined two kind of polymer onto thinner cobalt-chromium backbone (60um) compared with earlier type of DES. The BIOlute® active component is a bioabsorbable polymer matrix combined with an anti-proliferative drug, sirolimus, that is released in a controlled manner leaving only the PROBIO® coated stent in the long-term. The PROBIO® passive coating encapsulates the stent and eliminates interaction between the metal stent and the surrounding tissue. To date, Orsiro stent showed excellent results in terms of late lumen loss at 9 months in first-in-man single arm trial comparing the historical results of other DES (BIOFLOW-I trial), and RCT with non-inferiority design, comparing late lumen loss at 9 months of Orsiro versus everolimus-eluting stent (Xience prime®) is ongoing (BIOFLOW-II trial). However, there have been no trials comparing the Orsiro stent versus the Biomatrix stent (Biosensors Inc, Newport Beach, CA, USA).

This multicenter, randomized, open label, parallel arm study will evaluate whether the innovative newer generation stent, Orsiro hybrid DES, is non-inferior to the third generation stent, Biomatrix stent, in terms of 18 months late lumen loss.

• Study Type: Interventional
• Enrollment (Actual): 2341
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Gyeonggi
    • Seongnam, Gyeonggi, Korea, Republic of, 463-707
      • Seoul National Universtiy Bundang Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 83 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. General Inclusion Criteria

   1. Subject must be at least 18 years of age.
   2. Subject is able to verbally confirm understandings of risks, benefits and treatment alternatives of receiving the Biomatrix flex stents or Orsiro stents, and he/she or his/her legally authorized representative provides written informed consent prior to any study related procedure.
   3. Subject must have significant lesion (>50% by visual estimate) in any of the coronary arteries, venous or arterial bypass grafts.
   4. Subject must have evidence of myocardial ischemia (e.g., stable, unstable angina, recent infarction, silent ischemia, positive functional study or a reversible changes in the electrocardiogram (ECG) consistent with ischemia). In subjects with diameter stenosis > 70%, evidence of myocardial ischemia does not have to be documented.

2. Angiographic Inclusion Criteria

   1. Target lesion(s) must be located in coronary artery, venous or arterial bypass graft with diameter of ≥ 2.5 mm and ≤ 4.5 mm.
   2. Target lesion(s) must be amenable for percutaneous coronary intervention.

Exclusion Criteria:

1. The patient has a known hypersensitivity or contraindication to any of the following medications: Heparin, Aspirin, Clopidogrel, Cilostazol, Prasugrel, Ticagrelor, Biolimus, Sirolimus, Contrast media (Patients with documented sensitivity to contrast media which can be effectively premedicated with steroids and diphenhydramine [e.g. rash] may be enrolled. Those with true anaphylaxis to prior contrast media, however, should not be enrolled.)
2. Systemic (intravenous) Biolimus or Sirolimus use within 12 months.
3. Female of childbearing potential, unless a recent pregnancy test is negative, who possibly plan to become pregnant any time after enrollment into this study.
4. History of bleeding diathesis, known coagulopathy (including heparin- induced thrombocytopenia), abnormal hemogram (Hb<10g/dL or PLT count <100,000/μL) or will refuse blood transfusions
5. Patients with severe LV systolic dysfunction (LVEF<25%) or cardiogenic shock
6. Gastrointestinal or genitourinary bleeding within the prior 2 months, or major surgery within 2 months.
7. Non-cardiac co-morbid conditions are present with life expectancy <1 year or that may result in protocol non-compliance (per site investigator's medical judgment).
8. Patients who are actively participating in another drug or device investigational study, which have not completed the primary endpoint follow- up period.
9. Symptomatic heart failure

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: Orsiro drug eluting stent	Device: Orsiro drug eluting stent; Orsiro Hybrid drug eluting stent; Other Names: Orsiro drug eluting stent (Biotronik AG, Bulach, Switzeland)
Active Comparator: Biomatrix drug eluting stent	Drug: Biomatrix drug eluting stent; Biomatrix Flex drug eluting stent; Other Names: Biomatrix drug eluting stent (Biosensors,Newport Beach,USA)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Target lesion failure (TLF)	TLF is a composite of cardiac death, target vessel-related myocardial infarction and ischemia-driven target lesion revascularization as measured by percent of participants with adverse events	18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All death	All-cause death as measured by percent of participants with adverse events	18 months
All death	All-cause death as measured by percent of participants with adverse events	36 months
Cardiac death	cardiac death as measured by percent of participants with adverse events	18 months
Cardiac death	cardiac death as measured by percent of participants with adverse events	36 months
Target vessel-related MI and all MI	Target vessel-related MI and all MI as measured by percent of participants with adverse events subdivided as q wave and non-q wave	18 months
Target vessel-related MI and all MI	Target vessel-related MI and all MI as measured by percent of participants with adverse events subdivided as q wave and non-q wave	36 months
Stent thrombosis	Stent thrombosis (definite/possible/probable) as measured by percent of participants with adverse events	18 months
Stent thrombosis	Stent thrombosis (definite/possible/probable) as measured by percent of participants with adverse events	36 months
Net clinical outcome including bleeding (major and minor) as measured by percent	Net clinical outcome including bleeding (major and minor) as measured by percent of participants with adverse events	18 months
Net clinical outcome including bleeding (major and minor) as measured by percent	Net clinical outcome including bleeding (major and minor) as measured by percent of participants with adverse events	36 months
In-stent & In-segment late loss	In-stent & In-segment late loss as measure by post-PCI and F/U QCA	18 months
In-stent & In-segment late loss	In-stent & In-segment late loss as measure by post-PCI and F/U QCA	36 months
In-stent & In-segment % diameter stenosis	In-stent & In-segment % diameter stenosis as measure by post-PCI and F/U QCA	18 months
In-stent & In-segment % diameter stenosis	In-stent & In-segment % diameter stenosis as measure by post-PCI and F/U QCA	36 months
Degree of stent strut endothelialization and malapposition on OCT	Degree of stent strut endothelialization and malapposition on OCT as measure by post-PCI and F/U OCT analysis	18 months
Degree of stent strut endothelialization and malapposition on OCT	Degree of stent strut endothelialization and malapposition on OCT as measure by post-PCI and F/U OCT analysis	36 months
Target lesion failure (TLF)	TLF is a composite of cardiac death, target vessel-related myocardial infarction and ischemia-driven target lesion revascularization as measured by percent of participants with adverse events	36 months

Collaborators and Investigators

• Sponsor: Seoul National University Bundang Hospital
• Collaborators: Korea University Anam Hospital; Korea University Guro Hospital; Gachon University Gil Medical Center; The Catholic University of Korea; Gangnam Severance Hospital; Chungnam National University Hospital; Wonju Severance Christian Hospital; KangWon National University Hospital; Kosin University Gospel Hospital
• Investigators: Principal Investigator: In-Ho Chae, MD, Seoul National University Bundang Hospital

Publications and helpful links

General Publications

• Hamon M, Niculescu R, Deleanu D, Dorobantu M, Weissman NJ, Waksman R. Clinical and angiographic experience with a third-generation drug-eluting Orsiro stent in the treatment of single de novo coronary artery lesions (BIOFLOW-I): a prospective, first-in-man study. EuroIntervention. 2013 Jan 22;8(9):1006-11. doi: 10.4244/EIJV8I9A155.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2014
• Primary Completion (Actual): June 1, 2019
• Study Completion (Actual): September 1, 2019

Study Registration Dates

• First Submitted: November 17, 2014
• First Submitted That Met QC Criteria: November 21, 2014
• First Posted (Estimate): November 24, 2014

Study Record Updates

• Last Update Posted (Actual): September 25, 2019
• Last Update Submitted That Met QC Criteria: September 23, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: Coronary artery disease; Biomatrix drug eluting stent; Orsiro drug eluting stent
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Ischemia
• Other Study ID Numbers: B1403-244-002