Thiazolidinediones Or Sulphonylureas and Cardiovascular Accidents.Intervention Trial (TOSCA IT)

This study is currently recruiting participants.
Verified August 2012 by Italian Society of Diabetology
Sponsor:
Collaborators:
Associazione Medici Diabetologi (AMD)
Associazione Nazionale Medici Cardiologi Ospedalieri (ANMCO)
Information provided by (Responsible Party):
Italian Society of Diabetology
ClinicalTrials.gov Identifier:
NCT00700856
First received: June 18, 2008
Last updated: August 20, 2012
Last verified: August 2012
  Purpose

Background: In patients with type 2 diabetes inadequately controlled with metformin, two main therapeutic options are equally plausible: add-on a sulfonylurea (SU) or a thiazolidinedione (TZD). Since the two classes of drugs clearly differ in terms of mechanisms of action, side effects, economic costs and cardiovascular risk factors profile, a direct comparison of the two therapeutic strategies would be most appropriate.

Aims: 1) To evaluate the effects of add-on pioglitazone as compared with add-on a SU on the incidence of cardiovascular events in type 2 diabetic patients inadequately controlled with metformin; 2) To compare the two treatments in terms of glycemic control, safety, and economic costs.

Methods: multicentre, randomised, open label, parallel group trial of 48 months duration. Eligible participants (type 2 diabetic males and females, aged 50-75 years, BMI 20-45 Kg/m2, in treatment for the last two months with metformin 2 gr/die in monotherapy and with HbA1c > =7.0% and <= 9.0%) will be randomized to add-on: a SU - glibenclamide (5-15 mg/die), gliclazide (30-120 mg/die), glimepiride (2-6 mg/die), chosen according to local practice - or pioglitazone (15-45 mg/die). A HbA1c value > 8.0 % on two consecutive occasions will lead to addition of insulin to ongoing oral therapy.

Primary efficacy outcome: a composite endpoint of all-cause mortality, non fatal MI (including silent MI), non fatal stroke, and unplanned coronary revascularization.

Secondary outcomes. Principal secondary outcome: a composite ischemic endpoint of sudden death, fatal and non fatal acute MI (including silent MI), fatal and non fatal stroke, major amputations (above ankle), endovascular or surgical intervention on the coronary, leg or carotid arteries.

Other secondary outcomes

- a composite cardiovascular end point including the primary end point plus hospitalization for heart failure, endovascular or surgical intervention on the coronary, leg or carotid arteries, silent MI, angina - by WHO criteria and confirmed by a new electrocardiogram abnormality - intermittent claudication with an ankle/brachial index lower than 090; events of heart failure; a microvascular endpoint including: plasma creatinine increase of 2 times above the baseline value or creatinine clearance reduction of 20ml/min/1. 73m2 or development of overt nephropathy (dialysis or plasma creatinine >3,3 mg/dl) or macroalbuminuria; glycemic control (changes from baseline in HBA1c, time to failure of glycemic control, i.e., HBA1c >8.0% on two consecutive occasions three months apart); major CV risk factors (lipids, blood pressure, microalbuminuria, inflammation markers, waist circumference); safety and side effects; direct and indirect costs.

Data regarding CV endpoints, safety, tolerability, and study conduct will be monitored and analyzed by an independent committee, and will be not available to the study investigators until the closing of data collection. Efficacy end points will be analysed on an intention-to-treat basis.


Condition Intervention Phase
Type 2 Diabetes Mellitus
Cardiovascular Disease
Drug: add-on pioglitazone
Drug: add-on sulphonylurea
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Effects on Incidence of Cardiovascular Events of the Addition of Pioglitazone as Compared With a Sulphonylurea in Type 2 Diabetic Patients Inadequately Controlled With Metformin.

Resource links provided by NLM:


Further study details as provided by Italian Society of Diabetology:

Primary Outcome Measures:
  • A composite endpoint including: all-causes mortality, non fatal myocardial infarction (MI) - including silent MI- , non fatal stroke, unplanned coronary revascularization [ Time Frame: 48 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • A composite ischemic end point of: sudden death, fatal and non fatal MI (including silent MI), fatal and non fatal stroke, major leg amputation (above the ankle), endovascular or surgical interventions on the coronary, leg or carotid arteries [ Time Frame: 48 months ] [ Designated as safety issue: No ]
  • a composite CV endpoint including the primary endpoint plus heart failure, endovascular or surgical intervention on the coronary, leg or carotid arteries, angina, intermittent claudication with an ankle/brachial index < 0.85 [ Time Frame: 48 months ] [ Designated as safety issue: No ]
  • glycemic control (changes from baseline in HbA1c, time to failure of oral hypoglycaemic therapy, i.e., HBA1c >8.0% on two consecutive occasions three months apart) [ Time Frame: 48 months ] [ Designated as safety issue: No ]
  • major cardiovascular risk factors (lipids, blood pressure, microalbuminuria, inflammation markers, waist circumference) [ Time Frame: 48 months ] [ Designated as safety issue: No ]
  • development of nephropathy: plasma creatinine increase of 2 times above the baseline value or creatinine clearance reduction of 20ml/min/1. 73m2 or development of microalbuminuria or overt nephropathy (dialysis o plasma creatinine >3,3 mg/dl) [ Time Frame: 48months ] [ Designated as safety issue: No ]
  • events of heart failure evaluated according to the American Heart Association and the American Diabetes Association consensus on glitazones and heart failure [ Time Frame: 48 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 3371
Study Start Date: September 2008
Estimated Study Completion Date: December 2018
Estimated Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
metformin 2000 mg + pioglitazone 15-45 mg
Drug: add-on pioglitazone
participants randomised to this arm will add pioglitazone 15 mg/die to therapy with metformin (2 gr/die)
Active Comparator: 2
metformin 2000 mg + glibenclamide 5-15 mg or metformin 2000 mg + gliclazide 30-120 mg or metformin 2000 mg + glimepiride 2-6 mg
Drug: add-on sulphonylurea
participants randomized to this arm will add a sulphonylurea (glibenclamide 5 mg/die; gliclazide 30 mg/die or glimepiride 2 mg/die)to monotherapy with metformin (2 gr/die)

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   50 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Males and females, age 50-75 years
  • Type 2 diabetes of at least 2 years duration
  • BMI 20-45 Kg/m2
  • Stable treatment for the last two months with metformin in monotherapy (at least 2 gr/die)
  • HbA1c >=7.0% and <=9.0%

Exclusion Criteria:

  • Type 1 diabetes
  • Previous treatment with thiazolidinediones in the last six months
  • Contraindication/intolerance to metformin or SUs or TZDs
  • Documented coronary or cerebrovascular events in the previous 3 months
  • Serum creatinine > 1.5 mg/dl
  • History of congestive heart failure, NYHA I or higher
  • Chronic use of glucocorticoids
  • Ischemic ulcer or gangrene
  • Liver cirrhosis or severe hepatic dysfunction (ALT increase of 2.5 times the upper normal limit)
  • Pregnancy or breast feeding
  • Cancer, substance abuse, or any health problem that may interfere with the compliance to the study protocol or limit life expectancy
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00700856

Contacts
Contact: Gabriele Riccardi, Professor +390817462117 riccardi@unina.it

  Hide Study Locations
Locations
Italy
Ospedale Locatelli di Piario Recruiting
Seriate, Bergamo, Italy
Contact: Giosuè Ghialrdi, professor       giosue.ghilardi@bolognini.bg.it   
Principal Investigator: Giosuè Ghialrdi, professor         
Hospitaal of Treviglio Recruiting
Treviglio, Bergamo, Italy
Contact: Antonio Bossi, professor       antonio_bossi@ospedale.treviglio.bg.it   
Principal Investigator: Antonio Bossi, professor         
Hospital of Lanciano Recruiting
Lanciano, Chieti, Italy
Contact: Ercole D'Ugo         
Principal Investigator: Ercole D'Ugo         
Ospedale Casa Sollievo della Sofferenza Recruiting
San Giovanni Rotondo, Foggia, Italy
Contact: Salvatore De Cosmo, professor       sdecosm@tin.it   
Principal Investigator: Salvatore De Cosmo, professor         
ASL 4 - Chiavarese Recruiting
Chiavari, Genova, Italy
Contact: Laura Corsi, professor       lcorsi@asl4.liguria.it   
Principal Investigator: Laura Corsi, professor         
ASL 64 Recruiting
Eboli, Salerno, Italy
Contact: Biagio Tizio, professor       biagio.tizio@gmail.com   
Principal Investigator: Biagio Tizio, professor         
Presidio Ospedaliero Atri Recruiting
Atri, Teramo, Italy
Contact: Paolo Di Berardino, professor       dibera@yahoo.it   
Principal Investigator: Paolo Di Berardino, professor         
"Maggiore" Hospital Recruiting
Chieri, Turin, Italy
Contact: Carlo Bruno Giorda, Professor       diabetologia.dir@aslto5.piemonte.it   
Principal Investigator: Carlo Bruno Giorda, Professor         
Inrca - Irccs Recruiting
Ancona, Italy
Contact: Massimo Boemi, Professor       massimo.boemi@gmail.com   
Principal Investigator: Massimo Boemi, Professor         
San Donato Hospital Recruiting
Arezzo, Italy
Contact: Lucia Ricci, professor       lucia.ricci@usl8.toscana.it   
Principal Investigator: Lucia Arezzo, dr         
University of Bari Recruiting
Bari, Italy
Contact: Francesco Giorgino, Professor       giorginf@tin.it   
Principal Investigator: Francesco Giorgino, Professor         
Ospedali Riuniti di Bergamo Recruiting
Bergamo, Italy
Contact: Roberto Trevisan, Professor       rtrevisan@ospedaliriuniti.bergamo.it   
Principal Investigator: Roberto Trevisan, professor         
Policlinico S. Orsola Malpigli Recruiting
Bologna, Italy
Contact: Gabriele Forlani, professor       gabriele.forlani@aosp.bo.it   
Principal Investigator: Gabriele Forlani, professor         
Presidio Ospedaliero A.S.RE.Molise Recruiting
Campobasso, Italy
Contact: Antimo Aiello, professor       aantimo@virgilio.it   
Principal Investigator: Antimo Aiello, professor         
"Garibaldi di Nesima" Hospital Recruiting
Catania, Italy
Contact: Sebastiano Squatrito, Professor       squatri@tin.it   
Principal Investigator: Sebastiano Squatrito, Professor         
"Mater Domini" University Recruiting
Catanzaro, Italy
Contact: Agostino Gnasso         
Principal Investigator: Agostino Gnasso         
M. Bufalini Hospital Recruiting
Cesena, Italy
Contact: Costanza Santini, professor       csantini@ausl-cesena.emr.it   
Principal Investigator: Costanza Santini, professor         
ASP Recruiting
Cosenza, Italy
Contact: Vincenzo Asprino, professor       vincenzoasprino@libero.it   
Principal Investigator: Vincenzo Asprino, professor         
Arcispedale "S.Anna" Recruiting
Ferrara, Italy
Contact: Franco Tomasi, professor       f.tomasi@ospfe.it   
Principal Investigator: Franco Tomasi, professor         
University of Ferrara Recruiting
Ferrara, Italy
Contact: Franco Tomasi, Professor       f.tomasi@ospfe.it   
Principal Investigator: Franco Tomasi, Professor         
University of Florence Recruiting
Florence, Italy
Contact: Edoardo Mannucci, Professor       edoardo.mannucci@unifi.it   
Principal Investigator: Edoardo Mannucci, Professor         
Ospedali Riuniti Recruiting
Foggia, Italy
Contact: Mauro Cignarelli, professor       m.cignarelli@unifg.it   
Principal Investigator: Mauro Cignarelli, professor         
University of Genova Recruiting
Genova, Italy
Contact: Renzo Cordera, Professor       record@unige.it   
Principal Investigator: Renzo Cordera, Professor         
San Salvatore Hospital Recruiting
L'Aquila, Italy
Contact: Rossella Iannarelli, professor       rossella.iannarelli@alice.it   
Principal Investigator: Rossella Iannarelli, professor         
Santa Maria Goretti Hospital Recruiting
Latina, Italy
Contact: Raffaella Buzzetti, professor       raffaella.buzzetti@uniroma1.it   
Principal Investigator: Raffaella Buzzetti, professor         
ASL Latina Recruiting
Latina, Italy
Contact: Elisa Forte, professor       forte.elisa@gmail.com   
Principal Investigator: Elisa Forte, professor         
"Cittadella della Salute" Hospital Not yet recruiting
Lecce, Italy
Contact: Rosalia Serra         
Principal Investigator: Rosalia Serra         
ASL 6 Recruiting
Livorno, Italy
Contact: Graziano Di Cianni, professor       g.dicianni@usl6.toscana.it   
Principal Investigator: Graziano Di Cianni, professor         
Hospital of Massa Recruiting
Massa Carrara, Italy
Contact: Maria A. Dolci, professor       m.dolci@usl1.toscana.it   
Principal Investigator: Maria A. Dolci, professor         
Matera Hospital Recruiting
Matera, Italy
Contact: Angelo Venezia         
Principal Investigator: Angelo Venezia         
University of Messina Recruiting
Messina, Italy
Contact: Domenico Cucinotta, Professor       domenico.cucinotta@unime.it   
Principal Investigator: Domenico Cucinotta, Professor         
"Ospedali Riuniti Papardo-Piemonte" Hospital Recruiting
Messina, Italy
Contact: Francesco Ragonese         
Principal Investigator: Francesco Ragonese         
Niguarda Cà Grande Hospital Recruiting
Milan, Italy
Contact: Matteo Bonomo         
Principal Investigator: Matteo Bonomo         
Istituto Scientifico San Raffaele Recruiting
Milan, Italy
Contact: Piermarco Piatti, professor       piatti.piermarco@hsr.it   
Principal Investigator: Piermarco Piatti, professor         
"Federico II"University of Naples Recruiting
Naples, Italy, 80131
Contact: Angela A Rivellese, Prof    +390817462154    rivelles@unina.it   
Principal Investigator: Angela A Rivellese, Professor         
"Federico II" University Recruiting
Naples, Italy
Contact: Ciro Iovine, professor       iovine@unina.it   
Principal Investigator: Ciro Iovine, professor         
Second University Recruiting
Naples, Italy
Contact: Giuseppe Paolisso, professor       giuseppe.paolisso@unina2.it   
Principal Investigator: Giuseppe Paolisso, professor         
University of Padua Recruiting
Padua, Italy
Contact: Angelo Avogaro, Professor       angelo.avogaro@unipd.it   
Principal Investigator: Angelo Avogaro, Professor         
Complesso Sociosanitario dei Colli Recruiting
Padua, Italy
Contact: Annunziata lapolla         
Principal Investigator: Annunziata Lapolla         
University of Palermo Recruiting
Palermo, Italy
Contact: Carla Giordano         
Principal Investigator: Carla Giordano, Professor         
University of Parma Recruiting
Parma, Italy
Contact: Leone Arsenio, professor       larsenio@ao.pr.it   
Principal Investigator: Leone Arsenio, professor         
University of Perugia Recruiting
Perugia, Italy
Contact: Gabriele Perriello, Professor       gabriele.perriello@unipg.it   
Principal Investigator: Gabriele Perriello, Professor         
Civil Hospital Recruiting
Pescara, Italy
Contact: Agostino Consoli, Professor       consoli@unich.it   
Principal Investigator: Agostino Consoli, Professor         
Ospedale Gugliemo da Saliceto Recruiting
Piacenza, Italy
Contact: Donatella Zavaroni, professor       donatella.zavaroni@virgilio.it   
Principal Investigator: Donatella Zavaroni, professor         
University of Pisa Recruiting
Pisa, Italy
Contact: Stefano Del Prato, Professor       delprato@immr.med.unipi.it   
Principal Investigator: Stefano Del Prato, Professor         
Spedali Riuniti di Pistoia Recruiting
Pistoia, Italy
Contact: Roberto Anichini, professor       r.anichini@usl3.toscana.it   
Principal Investigator: Roberto Anichini, professor         
ASP Recruiting
Potenza, Italy
Contact: Giuseppe Citro, professor       giuseppe.citro@aspbasilicata.it   
Principal Investigator: Giuseppe Citro, professor         
Praia a Mare Hospital Recruiting
Praia a Mare, Italy
Contact: Luciano Tramontano, professor       lutram@libero.it   
Principal Investigator: Luciano Tramontano, professor         
Operative Unit of Diabetologia - ASL 4 Recruiting
Prato, Italy
Contact: Adolfo Arcangeli, Professor       adolfo.arcangeli@gmail.com   
Principal Investigator: Adolfo Arcangeli, Professor         
University of Ravenna Recruiting
Ravenna, Italy
Contact: Paolo Di Bartolo, Professor       p.dibartolo@ausl.ra.it   
Principal Investigator: Paolo Di Bartolo, Professor         
Ospedale Infermi Recruiting
Rimini, Italy
Contact: Annacarla Babini, professor       acbabini@auslrn.net   
Principal Investigator: Annacarla Babini, professor         
Policlinico di Tor Vergata Recruiting
Roma, Italy
Contact: Davide Lauro, professor       d.lauro@med.uniroma2.it   
Principal Investigator: Davide Lauro, professor         
Ospedale Pertini Recruiting
Roma, Italy
Contact: Sergio Leotta, professor       s.leotta@tiscali.it   
Principal Investigator: Sergio Leotta, professor         
Sant'Andrea Hospital Recruiting
Rome, Italy
Contact: Giuseppe Pugliese, Professor       giuseppe.pugliese@uniroma1.it   
Principal Investigator: Giuseppe Pugliese, Professor         
University of Siena Recruiting
Siena, Italy
Contact: Francesco Dotta, Professor       francesco.dotta@alice.it   
Principal Investigator: Francesco Dotta, Professor         
"San Matteo degli Infermi" Hospital Recruiting
Spoleto, Italy
Contact: Carlo lalli         
Principal Investigator: Carlo Lalli         
"Molinette" Hospital Recruiting
Turin, Italy
Contact: Paolo Cavallo Perin, Professor       paolo.cavalloperin@nito.it   
Principal Investigator: Paolo Cavallo Perin, Professor         
Azienda Ospedaliero Universitaria " S.Maria della Misericordia " Recruiting
Udine, Italy
Contact: Franco Grimaldi, professor       grimaldi.franco@aoud.sanita.fvg.it   
Principal Investigator: Franco Grimaldi, professor         
Hopital of Gallarate Recruiting
Varese, Italy
Contact: Ivano Franzetti         
Principal Investigator: Ivano Franzetti         
Civil Hospital Recruiting
Verona, Italy
Contact: Enzo Bonora, Professor       enzo.bonora@univr.it   
Principal Investigator: Enzo Bonora, Professor         
"G. Fracastoro" Civil Hospital Recruiting
Verona, Italy
Contact: Claudio Capra         
Principal Investigator: Claudio Capra         
Sponsors and Collaborators
Italian Society of Diabetology
Associazione Medici Diabetologi (AMD)
Associazione Nazionale Medici Cardiologi Ospedalieri (ANMCO)
Investigators
Study Chair: Gabriele Riccardi, Professor Italian Diabetes Society
Study Director: Olga Vaccaro, professor "FedericoII" University of Naples
Study Director: Maria Masulli, PhD "Federico II" University of Naples
  More Information

No publications provided by Italian Society of Diabetology

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Italian Society of Diabetology
ClinicalTrials.gov Identifier: NCT00700856     History of Changes
Other Study ID Numbers: FARM6T9CET
Study First Received: June 18, 2008
Last Updated: August 20, 2012
Health Authority: Italy: The Italian Medicines Agency

Keywords provided by Italian Society of Diabetology:
diabetes
cardiovascular disease
pioglitazone
sulphonylurea
metformin monotherapy
hypoglicaemic therapy

Additional relevant MeSH terms:
Cardiovascular Diseases
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Pioglitazone
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 17, 2014