Prn Budesonide/Formoterol Versus Regular Budesonide/Formoterol Plus Prn Terbutaline in Mild-Moderate Asthma

Condition(s) targeted: Asthma

Intervention: budesonide/formoterol combination (PRN) (Drug); budesonide/formoterol combination (Drug); placebo (Drug); terbutaline (Drug)

Phase: Phase 3

Status: Recruiting

Sponsored by: Universitaria di Ferrara

Official(s) and/or principal investigator(s):
Alberto Papi, MD, Principal Investigator, Affiliation: Universitaria di Ferrara

Overall contact:
Alberto Papi, MD, Phone: +390532210420, Email: ppa@unife.it

Study No. 001 about Budesonide/Formoterol use in ASthMA sponsored by Agenzia Italiana del FArmaco (Italian Drug Agency) (AIFA-ASMA-BF-001) The aim of the study is to verify whether asthma not controlled by low doses inhaled corticosteroids, thus in need for step up therapy, can be equally controlled by guidelines recommended regular bid treatment with long acting beta agonist/inhaled corticosteroid (ICS/LABA) combination or the symptom driven use of an ICS/LABA combination in the absence of maintenance therapy. The study is designed to be able to evaluate the non inferiority of regular placebo plus prn inhaled budesonide/formoterol (experimental treatment) versus regular, twice daily 160/4. 5 mcg inhaled budesonide/formoterol combination plus prn inhaled terbutaline (guidelines recommended treatment).

Official title: As Needed Budesonide/Formoterol Combination Versus Regular Budesonide/Formoterol Combination Plus Pas Needed Terbutaline in Mild-Moderate Persistent Asthma

Study design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator), Parallel Assignment, Efficacy Study

Primary outcome: comparison between groups of the relative risk for treatment failure

Secondary outcome:

number of treatment failures and of drop-out

time to first treatment failure and to drop-out

differences between groups of lung function parameters, quality of life, symptoms score, use of as needed medication, adverse events

Detailed description: Asthma is a problem worldwide, with an estimated 300 million affected individuals. There is evidence that asthma prevalence has been increasing in the last decades in some countries, including Italy. Analyses of the cost of asthma lead to conclude that the burden of the disease depend on the extent to which exacerbations are avoided since emergency treatment is more expensive than regular treatment.

Based on solid evidence, international guidelines recommend regular treatment with low dose ICS for mild persistent asthma and treatment with combination therapy [low dose ICS plus long-acting beta2-agonists (LABA)] for patients with asthma not controlled by low doses ICS alone. Recent studies have undermined the axiom that treatment with ICS must be regular to achieve and maintain asthma control, as equivalent control has been obtained either with prn use of an inhaled combination of a short acting beta2 agonist (SABA) and an ICS, or with a short course of 10 days high dose ICS at the start of exacerbations. In moderate-severe asthma regularly treated with inhaled ICS/LABA combination, the symptom-driven use of the same inhaled ICS/LABA combination as reliever is superior to the symptom-driven use of SABA or LABA alone.

Minimum age: 18 Years. Maximum age: 65 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Male or female out-patient aged from 18 years to 65 years

- Clinical diagnosis of moderate persistent asthma for at least 6 months, according to

GINA revised version 2006 guidelines

- Post-bronchodilator forced expiratory volume (FEV1) at least 80% of the predicted

- Either positive methacholine challenge test (PC20 FEV1< 4mg/ml or PD20 FEV1<0. 8 mg)

or positive response to the reversibility test in the last year

- Asthma either not adequately controlled with low-dose (≤500 mcg beclomethasone or

equivalent) inhaled corticosteroids (ICS) or controlled by bid inhaled combination of low-dose ICS/long acting beta-2 agonists (LABA)

- A co-operative attitude and ability to be trained to correctly use the dry powder

inhalator and to complete the diary cards

- Written informed consent obtained

Exclusion Criteria:

- Inability to carry out pulmonary function testing

- Moderate severe asthma associated with reduced lung function

- History of near-fatal asthma and/or admission intensive care unit because of asthma

- 3 or more courses of oral corticosteroids or hospitalization for asthma during the

previous year

- Diagnosis of COPD as defined by the GOLD guidelines

- Evidence of severe asthma exacerbation or symptomatic infection of the airways in the

previous 8 weeks

- Current smokers or recent (less than one year) ex-smokers, defined as smoking at

least 10 pack/years

- History or current evidence of heart failure, coronary artery disease, myocardial

infarction, severe hypertension, or cardiac arrhythmias

- Diabetes mellitis

- Percutaneous transluminal coronary angioplasty (PTCA) or coronary artery by-pass

graft (CABG) during the previous six months

- Abnormal ECG

- Clinically significant or unstable concurrent diseases: uncontrolled hyperthyroidism,

significant hepatic impairment, poorly controlled pulmonary disease (tuberculosis, active mycotic infection of the lung), gastrointestinal (e. g., active peptic ulcer), neurological or haematological autoimmune diseases

- Malignancy

- Any chronic diseases with prognosis < 2 years

- Pregnant or lactating females or not able to exclude pregnancy during the study

period

- History of alcohol or drug abuse

- Patients treated with monoamine oxidase inhibitors, tricyclic antidepressants or

beta-blockers as regular use

- Allergy, sensitivity or intolerance to study drugs and/or study drug formulation

ingredients

- Patients unlikely to comply with the protocol or unable to understand the nature,

scope and possible consequences of the study

- Patients who received any investigational new drug within the last 12 weeks

- Patients who have been previously enrolled in this study

Alberto Papi, MD, Phone: +390532210420, Email: ppa@unife.it

Seconda Università degli stuidi di Napoli, unità Operativa di Pneumologia, Napoli, Italy; Not yet recruiting
Antonio S Marsico, MD, Phone: +390815453017, Email: serafino.marsico@unina2.it

Università di Roma Tor Vergata, unità di malattie dell'apparato Respiratorio, Roma, Italy; Not yet recruiting
Mario Cazzola, MD, Phone: +390655170461, Email: mario.cazzola@uniroma2.it

Servizio Pneumologico ASL Brindisi, Brindisi, Italy; Not yet recruiting
Eugenio Sabato, MD, Phone: +390831.536525, Email: esabato@qubisoft.it

Fondazione S. Maugeri - IRCCS -dipartimento di Pneumologia riabilitativa, Cassano delle Murge, BA, Italy; Not yet recruiting
Antonio Spanevello, MD, Phone: +390807814111, Email: aspanevello@quisoft.it

Policlinico Sant'Orsola Malpighi, Unità Operativa di Pneumologia, Bologna, BO, Italy; Not yet recruiting
Mario Schiavina, MD, Phone: +390516363111, Email: mario.schiavina@aosp.bo.it

Università degli Studi di Catania, Unità operativa di Pneumologia, Catania, CT, Italy; Recruiting
Nunzio Crimi, MD, Phone: +390957593535, Email: crimi@unict.it

Università Magna Grecia Catanzaro, unità operativa di Pneumologia, Catanzaro, CZ, Italy; Recruiting
Rosario Maselli, MD, Phone: +3909613647171, Email: rmaselli@unicz.it

Ospedale Morgagni Pierantoni, azienda Ospedaliera di Forlì, Unitaà operativa di Pneumologia, Forlì, FC, Italy; Not yet recruiting
Fiorino Fiorentini, MD, Phone: +39054376123, Email: ffiorent@ausl.fo.it

UNIVERSITà Degli Studi Di Ferrara, Clinica Di Malattie Dell'Apparato Respiratorio, FERRARA, FE 44100, Italy; Not yet recruiting
Alberto Papi, MD, Phone: +390532210420, Email: ppa@unife.it
Alessandro Zanforlin, MD, Sub-Investigator
Brunilda Marku, MD, Sub-Investigator

Università degli studi di Foggia, ospedale pneumologico D'Avanzo, unità operativa di malattie dell'apparato respiratorio, Foggia, FG, Italy; Recruiting
Maria Pia Foschino, MD, Phone: +390881617832, Email: mfoschino@qubisoft.it

Università degli studi di Genova, Unità operativa di Pneumologia, Genova, Ge, Italy; Recruiting
Giorgio W Canonica, MD, Phone: +3901035385933, Email: canonica@unige.it

Ospedale città di Sesto San Giovanni, Unità operativa di Pneumologia, Sesto San Giovanni, MI, Italy; Recruiting
Antonio Foresi, MD, Phone: +390226257356, Email: antonio.foresi@aovimercate.org

Ospadale San Carlo Borromeo - Unità operativa di Pneumologia, Milano, MI, Italy; Not yet recruiting
Sandro Amaducci, MD, Phone: +390240222522, Email: amaducci.sandro@sancarlo.mi.it

Università di Modena e Reggio Emilia, Unità operativa di Pneumologia, Modena, MO, Italy; Not yet recruiting
Leonardo M Fabbri, MD, Phone: +390594222198, Email: fabbri.leonardo@unimore.it

Università degli studi di Padova, dipartimento di Pneunmologia, Padova, PD, Italy; Recruiting
Marina Saetta, MD, Phone: +390498213732, Email: marina.saetta@unipd.it

Università degli studi di Padova, Medicina del Lavoro, Padova, PD, Italy; Recruiting
Piero Maestrelli, MD, Phone: +390498212564, Email: piero.maestrelli@unipd.it

Università degli studi di Pisa, Ospedale Cisanello, unità operativa di Pneumologia, Pisa, PI, Italy; Recruiting
Pierluigi Paggiaro, MD, Phone: +39050995266, Email: ppaggiaro@qubisoft.it

Università degli stiudi di Parma, unità operativa di Pneumologia, Parma, PR, Italy; Recruiting
Dario Olivieri, MD, Phone: +390521290577, Email: olivieri@unipr.it

Università degli studi di Pavia, dipartimento di Pneumologia, Pavia, PV, Italy; Recruiting
Ernesto Pozzi, MD, Phone: +390382422232, Email: ernesto.pozzi@unipv.it

IRCCS Fondazione S Maugeri, Dipartimento di Allergologia, Pavia, PV, Italy; Recruiting
Gianna Moscato, MD, Phone: +390382592941, Email: moscato@fsm.it

Università Cattolica del Sacro Cuore, Policlinico Gemelli, unità operativa di Pneumologia, Roma, RM, Italy; Recruiting
Salvatore Valente, MD, Phone: +390630154335, Email: svalente@rm.unicatt.it

università Cattolica del Sacro Cuore, Columbus, unità operativa di allergologia, Roma, RM, Italy; Recruiting
Antonino Romano, MD, Phone: +39063503782, Email: romano@rm.unicatt.it

Università Roma La Sapienza, servizio di Fisiopatologia respiratoria, Roma, Rm, Italy; Not yet recruiting
Paolo Palange, MD, Phone: +390649972082, Email: paolo.palange@uniroma1.it

Ospadale di Cava de' Tirreni, Unità operativa di Fisiopatologia Respiratoria, Cava de' Tirreni, SA, Italy; Not yet recruiting
Mario Polverino, MD, Phone: +390894455365, Email: mpolverino@qubisoft.it

Università di Perugia -Terni, Medcina del lavoro Terni, Terni, TI, Italy; Recruiting
Andrea Siracusa, MD, Phone: +390744205554, Email: asiracus@unipg.it

Ospedale di Cattinara, unità operativa di pneumologia, Trieste, TS, Italy; Not yet recruiting
Marco Confalonieri, MD, Phone: +390403993136, Email: marco.confalonieri@aots.sanita.fvg.it

azienda universitaria-ospedaliera istituti ospitalieri di Verona, unità operativa di Allergologia, Verona, VR, Italy; Not yet recruiting
Gianenrico Senna, MD, Phone: +390458122347, Email: gianenrico.senna@mail.azosp.vr.it

Ospedale di Bussolengo, Unità operativa di Pneumologia, Bussolengo, VR, Italy; Not yet recruiting
Roberto W Dal Negro, MD, Phone: +390456712193, Email: rdalnegro@ulss22.ven.it

Ospedale regionale Umberto I, Unità Operativa di Allergologia, Ancona, an, Italy; Not yet recruiting
Floriano Bonifazi, MD, Phone: +390715963251, Email: f.bonifazi@ao-umbertoprimo.marche.it

Università degli studi di Torino, Dipartimento di scienze biomediche ed oncologia umana, Torino, to, Italy; Recruiting
Caterina Bucca, MD, Phone: +390116336748, Email: caterina.bucca@unito.it

Starting date: April 2009
Ending date: October 2011
Last updated: June 11, 2009