Efficacy and Safety of Nano+ Polymer-free Sirolimus-Eluting Stent: A Optical Coherent Tomography Study

Efficacy and Safety of Nano+ Polymer-free Sirolimus-Eluting Stent in the Treatment of Patients With De Novo Lesion: A Optical Coherent Tomography Prospective, Multicenter Study

Our hypothesis is to test that 1) The safety and efficacy of Nano+ DES in patients with de novo lesions; 2) A low neointimal hyperplasia after Nano+ DES implantation due to its effective and sufficient antiproliferative drug; 3) A very high coverage and an improved early arterial healing after Nano+ DES implantation due to polymer-free; 4) The safety of clopidogrel treatment discontinuation at 3 months when OCT results are defined as optimal.

Study Overview

• Status: Unknown
• Conditions: Coronary Artery Disease
• Intervention / Treatment: Device: Nano+ DES

Detailed Description

Eligibility criteria:

• 18 to 85 years.
• Evidence of myocardial ischemia without raised troponin (e.g. stable or unstable angina, silent ischemia demonstrated by positive territorial functional study).
• The patient has a planned intervention of up to two de novo lesions in different epicardial vessels
• Lesion(s) must have a visually estimated diameter stenosis of ≥50% and <100%.
• Lesion length must be <18mm
• RVD must be between 2.5-4.0 mm
• Written informed consent.
• The patient and the patient's physician agree to the follow-up visits including angiographic follow-up and OCT assessment at 3 months.

Design details and outcomes This is a prospective, multicentre, single arm, open- label study, which will enroll a total of 45 patients in 5 European investigational sites. All patients will be treated with the Nano+ Polymer-free Sirolimus Coronary Stent System. All patients will undergo angiographic (QCA) investigation at baseline (pre- and post-procedure) and at 3 months follow-up. All patients will undergo OCT investigation at 3 months follow-up. OCT investigation will be performed at 6 months follow-up in those patients where the OCT criteria (coverage and stent apposition) were not met at 3 months OCT. Off-line OCT and angiographic data analysis will be undertaken by an independent core laboratory (Cardialysis BV, Rotterdam, The Netherlands) blinded to clinical and procedural characteristics of the patients and according to pre-set Standard Operating Procedures. All patients will be evaluated clinically at 3, 4, 5 months (for patients with 6 months OCT follow-up evaluation will be at 8 months) and at 1 and 2 years. Clinical data will be adjudicated by an independent Clinical Event Committee. An independent Data Safety and Monitoring Board (DSMB) will monitor the individual and collective safety of the patients in the study on an ongoing basis. This is a hypothesis generating study, because no evidence about the expected magnitude of the effect is available at present. Data generated from this study will be compared (historical control) against historical figures of other drug eluting stents available at Cardialysis, for published data.

• Study Type: Interventional
• Enrollment (Anticipated): 45
• Phase: Phase 4

Contacts and Locations

Study Locations

• Belgium
  • Hasselt, Belgium, B-3500
    • Recruiting
    • UZ Virga Jesse Ziekenhuis
    • Contact: E Benit, Dr; Phone Number: 0032 11 309 440; Email: edouard.benit@virgajesse.be
    • Principal Investigator: E Benit, Dr
  • Liège, Belgium, B-4000
    • Recruiting
    • CHU Sart Tillman
    • Contact: V Legrand, Prof; Phone Number: 0032 4 366 71 92; Email: vlegrand@chu.ulg.ac.be
    • Principal Investigator: V Legrand, Prof
• Netherlands
  • Enschede, Netherlands, 7511
    • Recruiting
    • Medisch Spectrum Twente
    • Contact: C von Birgelen, Dr; Phone Number: 0031 53 487 21 05; Email: C.vonBirgelen@mst.nl
    • Principal Investigator: C von Birgelen, Dr
  • Leeuwarden, Netherlands, 8934
    • Recruiting
    • Medisch Centrum Leeuwarden
    • Contact: S Hofma, Dr; Phone Number: 0031 58 286 66 66; Email: S.H.Hofma@ZNB.NL
    • Principal Investigator: S Hofma, Dr
  • Rotterdam, Netherlands, 3015
    • Recruiting
    • Erasmus Medical Centre
    • Contact: R.J.M van Geuns, Dr; Phone Number: 0031 10 703 33 48; Email: r.vangeuns@erasmusmc.nl
    • Principal Investigator: R.J.M van Geuns, Dr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 18 to 85 years.
• Evidence of myocardial ischemia without raised troponin (e.g. stable or unstable angina, silent ischemia demonstrated by positive territorial functional study).
• The patient has a planned intervention of up to two de novo lesions in different epicardial vessels
• Lesion(s) must have a visually estimated diameter stenosis of ≥50% and <100%.
• Lesion length must be <18mm
• RVD must be between 2.5-4.0 mm
• Written informed consent.
• The patient and the patient's physician agree to the follow-up visits including angiographic follow-up and OCT assessment at 3 months.

Exclusion Criteria:

• Evidence of ongoing acute myocardial infarction in ECG prior to procedure.
• LVEF <30%.
• Platelet count <100,000 cells/mm3 or >700,000 cells/mm3, a WBC of <3,000 cells/mm3, or documented or suspected liver disease (including laboratory evidence of hepatitis).
• Known renal insufficiency (e.g., eGFR <60 ml/kg/m2 or serum creatinine level of >2.5 mg/dL, or subject on dialysis).
• History of bleeding diathesis or coagulopathy.
• The patient is a recipient of a heart transplant.
• Known hypersensitivity or contraindication to aspirin, both heparin and bivalirudin, antiplatelet medication specified for use in the study (clopidogrel prasugrel, ticagrelor and ticlopidine), sirolimus or stainless steel.
• Other medical illness (e.g. cancer, stroke with neurological deficiency) or known history of substance abuse (alcohol, cocaine, heroin etc.) as per physician judgment that may cause non-compliance with the protocol or confound the data interpretation or is associated with a limited life expectancy
• Participating in other drugs or medical devices clinical trials, prior to reaching the primary endpoint.
• Pregnant or breastfeeding woman or woman in fertile period not taking adequate contraceptives

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: NANO+ DES; The Nano+ Polymer-free Sirolimus-Eluting Coronary Stent System is device/drug combination products consisting of a drug-coated stent and a balloon expandable delivery system. The stent is coated with a formulation containing rapamycin, the active ingredient, adhered to 316L stainless bare stent scaffold with submicron micropores, and is approved by State Food and Drug Administration of China in 2011(No. 3460037).

Device: Nano+ DES; All patients will be treated with the NanoTM Polymer-free Sirolimus Coronary Stent System. All patients will undergo angiographic (QCA) investigation at baseline (pre- and post-procedure) and at 3 months follow-up. All patients will undergo OCT investigation at 3 months follow-up. All patients will be evaluated clinically at 3, 4, 5 months (for patients with 6 months OCT follow-up evaluation will be at 8 months) and at 1 and 2 years.; Other Names: NANO+ Polymer-free Sirolimus-Eluting Stent

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
In-stent neointimal hyperplasia volume obstruction (%)	For those patients that did not achieve the optimal/ successful OCT criteria at 3 months an additional OCT investigation will be planned at 6 months follow-up where these same endpoints will be assessed.	3-month

Secondary Outcome Measures

Outcome Measure	Time Frame
Neointimal hyperplasia area/volume	3-month
Mean/Minimal Stent diameter/area/volume	3-month
Mean/Minimal Lumen diameter/area/volume	3-month
Mean/maximal thickness of the struts coverage	3-month
Percentage of covered struts	3-month
Incomplete strut apposition	3-month

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
MLD and %DS	All measurements will be made of the in-stent, in-segment, proximal and distal stent margins.	3-month
Late Lumen Loss	The difference between the minimum lumen diameter (MLD) post procedure and the MLD at 3 month follow-up.	3-month
Binary Restenosis (DS ≥50%)		3-month
Acute success	Acute success will be classified according to the following definitions: Device success: < 30% residual stenosis (by on-line QCA); Procedure success: The attainment of < 30% residual stenosis by QCA AND either a TIMI flow 3 or a consistent TIMI flow 2 before and after the procedure, using any percutaneous method without the occurrence of MACE during the hospital stay. These measurements will be made by the independent angiographic core laboratory. If the core laboratory is unable to assess the % residual stenosis, the investigator's assessment as recorded in the CRF will be used for the statistical analysis.	3 month
Device-oriented Composite Endpoints and its individual component	Device-oriented Composite Endpoint (DoCE) is defined as cardiac death, MI not clearly attributable to a non-intervention vessel, and clinically-indicated target lesion revascularization	up to 2 years
Stent thrombosis	According to the ARC definitions	up to 2 years

Collaborators and Investigators

• Sponsor: Lepu Medical Technology (Beijing) Co., Ltd.
• Investigators: Study Chair: Patrick W Serruys, PhD, Erasmus Medical Center; Principal Investigator: Run-Lin Gao, MD, Fu Wai Hospital, Beijing, China; Principal Investigator: Bo Xu, MSc, Fu Wai Hospital, Beijing, China; Principal Investigator: Yao-Jun Zhang, PhD, The First Affiliated Hospital with Nanjing Medical University

Study record dates

Study Major Dates

• Study Start: July 1, 2013
• Primary Completion (Anticipated): July 1, 2016
• Study Completion (Anticipated): November 1, 2016

Study Registration Dates

• First Submitted: August 4, 2013
• First Submitted That Met QC Criteria: August 15, 2013
• First Posted (Estimate): August 19, 2013

Study Record Updates

• Last Update Posted (Estimate): December 15, 2015
• Last Update Submitted That Met QC Criteria: December 14, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Keywords: OCT; DAPT; Nano+ DES; Neointimal hyperplasia; 3 month
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Coronary Artery Disease; Physiological Effects of Drugs; Anti-Infective Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antifungal Agents; Sirolimus
• Other Study ID Numbers: 120025