Balloon Elution and Late Loss Optimization (BELLO) Study (BELLO)

Balloon Elution and Late Loss Optimization (BELLO) Study: A Multicentre Randomized Study of the IN.PACT Falcon™ Paclitaxel Drug-eluting Balloon to Reduce Restenosis in Small Coronary Vessels

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.

Study Overview

• Status: Unknown
• Conditions: Coronary Artery Disease
• Intervention / Treatment: Device: IN.PACT Falcon paclitaxel eluting balloon (Drug eluting balloon); Device: Taxus (Paclitaxel eluting stent)

• Study Type: Interventional
• Enrollment (Actual): 182
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • MI
    • Milan, MI, Italy, 20100
      • Irccs Fondazione Centro S.Raffaele Del Monte Tabor

Participation Criteria

Eligibility Criteria

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

Description

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.

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: 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).	Device: IN.PACT Falcon paclitaxel eluting balloon (Drug eluting balloon); Coronary Artery Bypass Graft (CABG); Other Names: IN.PACT Falcon paclitaxel eluting balloon
Active Comparator: Control Arm PES; Control Arm: paclitaxel-eluting stent (PES) implantation as per standard practice.	Device: Taxus (Paclitaxel eluting stent); Percutaneous transluminal coronary angioplasty (PTCA) with stent

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Late Lumen Loss (LLL) at 6 months follow-up defined as the difference between postprocedural minimum luminal diameter and follow-up minimum luminal diameter, as assessed by quantitative coronary angiography	6 Month

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Fondazione Evidence per Attività e Ricerche Cardiovascolari ONLUS
• Investigators: Principal Investigator: Antonio Colombo, Dr., Irccs Fondazione Centro S.Raffaele Del Monte Tabor; Principal Investigator: Corrado Tamburino, Prof., Presidio Ospedaliero Ferrarotto di Catania; Principal Investigator: Patrizia Presbitero, Prof, Istituto Clinico Humanitas di Rozzano (MI); Principal Investigator: Alberta Pangrazi, Dr., Azienda Ospedaliera Ospedali Riuniti Umberto I-G.M.Lancisi-G.Salesi di Ancona; Principal Investigator: Roberto Violini, Dr., Azienda Ospedaliera San Camillo Forlanini di Roma; Principal Investigator: Francesca Buffoli, Dr., Ospedale "C.Poma" di Mantova; Principal Investigator: Maurizio Tespili, Dr., Azienda Ospedaliera "Bolognini" di Seriate; Principal Investigator: Fausto Castriota, Dr., Citta' di Lecce Hospital di Lecce; Principal Investigator: Alberto Cremonesi, Dr., Villa Maria Cecilia Hospital di Cotignola; Principal Investigator: Antonio Micari, Dr., Villa Maria Eleonora Hospital di Palermo; Principal Investigator: Alfredo Marchese, Dr., Casa di Cura "AntheaHospital" di Bari; Principal Investigator: Fabrizio Tomai, Dr., European Hospital di Roma; Principal Investigator: Massimo Margheri, Dr., Ospedale S.Maria delle Croci AUSL di Ravenna; Principal Investigator: Alberto Menozzi, Dr., Azienda Ospedaliero-Universitaria di Parma

Publications and helpful links

General Publications

• Latib A, Colombo A, Castriota F, Micari A, Cremonesi A, De Felice F, Marchese A, Tespili M, Presbitero P, Sgueglia GA, Buffoli F, Tamburino C, Varbella F, Menozzi A. A randomized multicenter study comparing a paclitaxel drug-eluting balloon with a paclitaxel-eluting stent in small coronary vessels: the BELLO (Balloon Elution and Late Loss Optimization) study. J Am Coll Cardiol. 2012 Dec 18;60(24):2473-80. doi: 10.1016/j.jacc.2012.09.020. Epub 2012 Nov 14. Erratum In: J Am Coll Cardiol. 2013 Apr 16;61(15):1660.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: March 1, 2010
• Primary Completion (Actual): March 1, 2012
• Study Completion (Anticipated): May 1, 2014

Study Registration Dates

• First Submitted: March 11, 2010
• First Submitted That Met QC Criteria: March 12, 2010
• First Posted (Estimate): March 15, 2010

Study Record Updates

• Last Update Posted (Estimate): August 14, 2013
• Last Update Submitted That Met QC Criteria: August 13, 2013
• Last Verified: August 1, 2013

More Information

Terms related to this study

• Keywords: coronary artery disease; paclitaxel PTCA drug-eluting balloon; provisional spot stenting; Late Lumen Loss; Minimal lumen diameter; coronary artery disease in a small vessel
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel; Albumin-Bound Paclitaxel
• Other Study ID Numbers: BELLO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No