Clinical trial NCT01086579: Balloon Elution and Late Loss Optimization (BELLO) Study
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Coronary Artery Disease
Keywords: paclitaxel PTCA drug-eluting balloon
provisional spot stenting
coronary artery disease
Late Lumen Loss
Minimal lumen diameter
coronary artery disease in a small vessel
Lead sponsor: Fondazione Evidence per Attività e Ricerche Cardiovascolari ONLUS
Sponsor class: OTHER
First posted: 2010-03-15
Enrollment: 182
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: 6 Month
Secondary outcomes:
measure: Device Success: ability of the Investigational Device to be delivered, dilate, and be retrieved from the target lesion.
timeFrame: day 1
measure: Procedural Success: defined as Device Success without the occurrence of Major Adverse Cardiac Events (MACE) during the index hospitalization
timeFrame: day 1
measure: MACE rate through 30 days, 6 months,1, 2, 3 years post index procedure
timeFrame: 30 days, 6 months,1, 2, 3 years
measure: Target Lesion Revascularization (TLR) at 6 months,1, 2, 3 years post index procedure
timeFrame: 6 months,1, 2, 3 years
measure: Target Vessel Revascularization (TVR) at 6 months,1, 2, 3 years post index procedure
timeFrame: 6 months,1, 2, 3 years
measure: Target vessel failure (TVF), defined as cardiac death, Myocardial Infarction (MI) or TVR at 1 year
timeFrame: 1 Year
measure: Binary Restenosis rate at 6 months follow-up
timeFrame: 6 months
Other outcomes:
Locations:
city: Milan
country: Italy
facility: Irccs Fondazione Centro S.Raffaele Del Monte Tabor
state: MI
Study officials:
affiliation: IRCCS Fondazione Centro S.Raffaele del Monte Tabor
name: Antonio Colombo, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Presidio Ospedaliero Ferrarotto di Catania
name: Corrado Tamburino, Prof.
role: PRINCIPAL_INVESTIGATOR
affiliation: Istituto Clinico Humanitas di Rozzano (MI)
name: Patrizia Presbitero, Prof
role: PRINCIPAL_INVESTIGATOR
affiliation: Azienda Ospedaliera Ospedali Riuniti Umberto I-G.M.Lancisi-G.Salesi di Ancona
name: Alberta Pangrazi, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Azienda Ospedaliera San Camillo Forlanini di Roma
name: Roberto Violini, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Ospedale "C.Poma" di Mantova
name: Francesca Buffoli, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Azienda Ospedaliera "Bolognini" di Seriate
name: Maurizio Tespili, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Citta' di Lecce Hospital di Lecce
name: Fausto Castriota, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Villa Maria Cecilia Hospital di Cotignola
name: Alberto Cremonesi, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Villa Maria Eleonora Hospital di Palermo
name: Antonio Micari, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Casa di Cura "AntheaHospital" di Bari
name: Alfredo Marchese, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: European Hospital di Roma
name: Fabrizio Tomai, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Ospedale S.Maria delle Croci AUSL di Ravenna
name: Massimo Margheri, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Azienda Ospedaliero-Universitaria di Parma
name: Alberto Menozzi, Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.