Clinical trial NCT02299011: Comparison of Biomatrix and Orsiro Drug Eluting Stent
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Coronary Artery Disease
Myocardial Ischemia
Keywords: Biomatrix drug eluting stent
Orsiro drug eluting stent
Coronary artery disease
Lead sponsor: Seoul National University Bundang Hospital
Sponsor class: OTHER
Collaborators: name: Wonju Severance Christian Hospital
name: Korea University Guro Hospital
name: Gangnam Severance Hospital
name: Chungnam National University Hospital
name: The Catholic University of Korea
name: Korea University Anam Hospital
name: Kosin University Gospel Hospital
name: KangWon National University Hospital
name: Gachon University Gil Medical Center
First posted: 2014-11-24
Enrollment: 2341
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Target lesion failure (TLF)
timeFrame: 18 months
Secondary outcomes:
measure: All death
timeFrame: 18 months
measure: All death
timeFrame: 36 months
measure: Cardiac death
timeFrame: 18 months
measure: Cardiac death
timeFrame: 36 months
measure: Target vessel-related MI and all MI
timeFrame: 18 months
measure: Target vessel-related MI and all MI
timeFrame: 36 months
measure: Stent thrombosis
timeFrame: 18 months
measure: Stent thrombosis
timeFrame: 36 months
measure: Net clinical outcome including bleeding (major and minor) as measured by percent
timeFrame: 18 months
measure: Net clinical outcome including bleeding (major and minor) as measured by percent
timeFrame: 36 months
measure: In-stent & In-segment late loss
timeFrame: 18 months
measure: In-stent & In-segment late loss
timeFrame: 36 months
measure: In-stent & In-segment % diameter stenosis
timeFrame: 18 months
measure: In-stent & In-segment % diameter stenosis
timeFrame: 36 months
measure: Degree of stent strut endothelialization and malapposition on OCT
timeFrame: 18 months
measure: Degree of stent strut endothelialization and malapposition on OCT
timeFrame: 36 months
measure: Target lesion failure (TLF)
timeFrame: 36 months
Other outcomes:
Locations:
city: Seongnam
country: Korea, Republic of
facility: Seoul National Universtiy Bundang Hospital
state: Gyeonggi
Study officials:
affiliation: Seoul National University Bundang Hospital
name: In-Ho Chae, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.