Balloon Elution and Late Loss Optimization (BELLO) Study

• Device Success: ability of the Investigational Device to be delivered, dilate, and be retrieved from the target lesion. [ Time Frame: day 1 ] [ Designated as safety issue: Yes ]
• Procedural Success: defined as Device Success without the occurrence of Major Adverse Cardiac Events (MACE) during the index hospitalization [ Time Frame: day 1 ] [ Designated as safety issue: Yes ]
• MACE rate through 30 days, 6 months,1, 2, 3 years post index procedure [ Time Frame: 30 days, 6 months,1, 2, 3 years ] [ Designated as safety issue: Yes ]
• Target Lesion Revascularization (TLR) at 6 months,1, 2, 3 years post index procedure [ Time Frame: 6 months,1, 2, 3 years ] [ Designated as safety issue: Yes ]
• Target Vessel Revascularization (TVR) at 6 months,1, 2, 3 years post index procedure [ Time Frame: 6 months,1, 2, 3 years ] [ Designated as safety issue: Yes ]
• Target vessel failure (TVF), defined as cardiac death, Myocardial Infarction (MI) or TVR at 1 year [ Time Frame: 1 Year ] [ Designated as safety issue: Yes ]
• Binary Restenosis rate at 6 months follow-up [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

Prospective multicentre randomized (1:1) investigator initiated study, in which consecutive patients undergoing percutaneous revascularization of small coronary vessels will be assigned to one of the two study arms:

1. Treatment Arm: IN.PACT Falcon™ paclitaxel drug-eluting balloon (DEB) dilatation and provisional spot bare-metal stenting (BMS).
2. Control Arm: paclitaxel-eluting stent (PES) implantation as per standard practice.

Eligible subjects with coronary artery disease in a small vessel (reference diameter<2.8mm) will be consecutively screened and enrolled based on the inclusion and exclusion criteria

The objective of the study is to assess the non-inferiority of the DEB to the PES as regards to primary endpoint of mean late lumen loss (LLL) at 6 months, defined as the difference between postprocedural minimum luminal (MLD) diameter and follow-up MLD, as assessed by quantitative coronary angiography and is based on the following assumptions:

1. The means of LLL in the 2 groups are precisely equal
2. A standard deviation in LLL of 0.5mm in both groups as demonstrated in the ISAR-SMART 3 and PEPCAD II trials
3. A non-inferiority margin of 0.25mm between groups is clinically unimportant

Based on these assumptions:

1. Null hypothesis (N0): mean LLL in DEB group is ≥0.25mm than that in the PES group (i.e. PES is superior to DEB)
2. Alternative hypothesis 1 (H1): mean LLL between DEB and PES is <0.25mm (i.e. DEB is non-inferior to PES)
3. Alternative hypothesis 2 (H2): mean LLL between DEB and PES <0 (i.e. DEB is superior to PES) Based on the above calculations, a sample size of 77 patients will be required in each group to show non-inferiority of DEB vs. PES with an α error of 0.025 (one-sided Z test) and a power of 80%. To account for a 20% rate of withdrawal, lost to follow-up or not presenting for follow-up angiography, a total of 182 patients (91 in each group) will be randomized.

• Device: IN.PACT Falcon paclitaxel eluting balloon (Drug eluting balloon)
  Coronary Artery Bypass Graft (CABG)
  Other Name: IN.PACT Falcon paclitaxel eluting balloon
• Device: Taxus (Paclitaxel eluting stent)
  Percutaneous transluminal coronary angioplasty (PTCA) with stent

• Experimental: Treatment Arm (IN.PACT Falcon Drug Eluting Balloon)
  IN.PACT Falcon™ paclitaxel drug-eluting balloon (DEB) dilatation and provisional spot bare metal stenting (Bare Metal Stent).
  Intervention: Device: IN.PACT Falcon paclitaxel eluting balloon (Drug eluting balloon)
• Active Comparator: Control Arm PES
  Control Arm: paclitaxel-eluting stent (PES) implantation as per standard practice.
  Intervention: Device: Taxus (Paclitaxel eluting stent)

Inclusion Criteria:

• Age > 18 years.
• Patient providing written informed consent.
• Patients with stable angina pectoris (Canadian Cardiovascular Society [CCS] 1, 2 3) or unstable angina pectoris with documented ischemia (CCS 4, Braunwald Class IB-C, IIB-C or IIIB-C), or patients with documented silent ischemia.
• Patients who are eligible for coronary revascularization (angioplasty and/or CABG).
• Female patients with child bearing potential must have a negative pregnancy test within one week before treatment and must use adequate contraception.

Angiographic Inclusion Criteria:

• Native coronary artery.
• De novo lesion.
• Reference vessel diameter < 2.8mm by visual estimate.
• Target lesion with a visually estimated stenosis >50%.
• Target lesion length < 25mm by visual estimate.
• A maximum of 2 epicardial vessels requiring revascularization.
• A maximum of 2 target lesions can be included (In the case of treatment of more than one lesion, the treatment selected will remain the same).

Exclusion Criteria:

• Patients unable to give informed consent.
• Patients enrolled in another study with any investigational drug or device within the past 30 days.
• Patients scheduled for a major surgical intervention within 6 months of enrolment in the study.
• Patients with acute (< 24h) or recent (≤ 48 hours) myocardial infarction.
• Patients with a contraindication to an emergency coronary bypass surgery.
• Any individual who may refuse a blood transfusion.
• Patients with serum creatinine >2.0mg/dL or >180umol/L.
• Patients with severe congestive heart failure.
• Patients who had a cerebral stroke <6 months prior to the Index Procedure.
• EF (Ejection Fraction) < 30%.
• Patients with any known allergy, hypersensitivity or intolerance to acetylsalicylic acid (ASA), Clopidogrel or Ticlopidine, Paclitaxel.
• Any known allergy to contrast medium that cannot be pre-treated.

Angiographic exclusion criteria:

• >2 epicardial vessels requiring revascularization.
• Target lesion distance from the ostium of left anterior descending coronary artery (LAD)/left circumflex coronary artery (LCX)/right coronary artery (RCA) is < 5 mm.
• Target lesion is located in either a venous or arterial graft.
• Target vessel contains a previously implanted stent.
• Angiographic evidence of thrombus at the target site.
• Chronic total occlusions.
• Restenotic lesions.
• Bifurcation lesions which the operator decides a 2-stent technique as intention-to-treat is required OR bifurcations with side branches ≥ 2.5mm.
• Failure to successfully treat non-target lesions within the target vessel (non-target lesions must be treated prior the target lesion).
• Greater than 2 non-target lesions treated during the index procedure.
• Previous Percutaneous Coronary Intervention (PCI) within the last 3 months.