Clinical trial NCT00849095: Prn Budesonide/Formoterol Versus Regular Budesonide/Formoterol Plus Prn Terbutaline in Mild-Moderate Asthma
Official title: As Needed Budesonide/Formoterol Combination Versus Regular Budesonide/Formoterol Combination Plus as Needed Terbutaline in Mild-Moderate Persistent Asthma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Asthma
Keywords: Adult
Asthma
Bronchodilator Agents
Budesonide
Double-Blind Method
Drug Therapy, Combination
Ethanolamines
Female
Forced Expiratory Volume
Humans
Male
Terbutaline
Lead sponsor: Università degli Studi di Ferrara
Sponsor class: OTHER
First posted: 2009-02-23
Enrollment: 860
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).

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.

Eligibility 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

Primary outcomes:
measure: comparison between groups of the relative risk for treatment failure
timeFrame: 52 weeks
Secondary outcomes:
measure: number of treatment failures
timeFrame: 52 weeks
measure: time to first treatment failure
timeFrame: 52 weeks
measure: differences between groups of lung function parameters, quality of life, symptoms score, use of as needed medication, adverse events
timeFrame: 52 weeks
Other outcomes:
Locations:
city: Ancona
country: Italy
facility: Ospedale regionale Umberto I, Unità Operativa di Allergologia
state: AN
city: Cassano delle Murge
country: Italy
facility: Fondazione S. Maugeri - IRCCS -dipartimento di Pneumologia riabilitativa
state: BA
city: Benevento
country: Italy
facility: Dipartimento di Scienze Mediche-Unità Operativa di Pneumologia
state: BN
city: Bologna
country: Italy
facility: Policlinico Sant'Orsola Malpighi, Unità Operativa di Pneumologia
state: BO
city: Catania
country: Italy
facility: Università degli Studi di Catania, Unità operativa di Pneumologia
state: CT
city: Catanzaro
country: Italy
facility: Università Magna Grecia Catanzaro, unità operativa di Pneumologia
state: CZ
city: Forlì
country: Italy
facility: Ospedale Morgagni Pierantoni, azienda Ospedaliera di Forlì, Unitaà operativa di Pneumologia
state: FC
city: Ferrara
country: Italy
facility: UNIVERSITà DEGLI STUDI DI FERRARA, CLINICA DI MALATTIE DELL'APPARATO RESPIRATORIO
state: FE
city: Foggia
country: Italy
facility: Università degli studi di Foggia, ospedale pneumologico D'Avanzo, unità operativa di malattie dell'apparato respiratorio
state: FG
city: Milano
country: Italy
facility: Ospadale San Carlo Borromeo - Unità operativa di Pneumologia
state: MI
city: Sesto San Giovanni
country: Italy
facility: Ospedale città di Sesto San Giovanni, Unità operativa di Pneumologia
state: MI
city: Modena
country: Italy
facility: Università di Modena e Reggio Emilia, Unità operativa di Pneumologia
state: MO
city: Palermo
country: Italy
facility: Università degli Studi di Palermo, Ospedale "V. Cervello"
state: Pa
city: Padova
country: Italy
facility: Università degli studi di Padova, dipartimento di Pneunmologia
state: PD
city: Padova
country: Italy
facility: Università degli studi di Padova, Medicina del Lavoro
state: PD
city: Pisa
country: Italy
facility: Università degli studi di Pisa, Ospedale Cisanello, unità operativa di Pneumologia
state: PI
city: Parma
country: Italy
facility: Università degli stiudi di Parma, unità operativa di Pneumologia
state: PR
city: Pavia
country: Italy
facility: IRCCS Fondazione S Maugeri, Dipartimento di Allergologia
state: PV
city: Pavia
country: Italy
facility: Università degli studi di Pavia, dipartimento di Pneumologia
state: PV
city: Roma
country: Italy
facility: università Cattolica del Sacro Cuore, Columbus, unità operativa di allergologia
state: RM
city: Roma
country: Italy
facility: Università Cattolica del Sacro Cuore, Policlinico Gemelli, unità operativa di Pneumologia
state: RM
city: Roma
country: Italy
facility: Università Roma La Sapienza, servizio di Fisiopatologia respiratoria
state: RM
city: Terni
country: Italy
facility: Università di Perugia -Terni, Medcina del lavoro Terni
state: TI
city: Torino
country: Italy
facility: Università degli studi di Torino, Dipartimento di scienze biomediche ed oncologia umana
state: TO
city: Trieste
country: Italy
facility: Ospedale di Cattinara, unità operativa di pneumologia
state: TS
city: Bussolengo
country: Italy
facility: Ospedale di Bussolengo, Unità operativa di Pneumologia
state: VR
city: Verona
country: Italy
facility: azienda universitaria-ospedaliera istituti ospitalieri di Verona, unità operativa di Allergologia
state: VR
city: Brindisi
country: Italy
facility: Servizio Pneumologico ASL Brindisi
city: Napoli
country: Italy
facility: Seconda Università degli stuidi di Napoli, unità Operativa di Pneumologia
city: Parma
country: Italy
facility: Giuseppina Bertorelli
city: Roma
country: Italy
facility: Università di Roma Tor Vergata, unità di malattie dell'apparato Respiratorio
Study officials:
affiliation: Università degli Studi di Ferrara
name: Alberto Papi, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Papi A, Marku B, Scichilone N, Maestrelli P, Paggiaro P, Saetta M, Nava S, Folletti I, Bertorelli G, Bertacco S, Contoli M, Plebani M, Barbaro MPF, Spanevello A, Aliani M, Pannacci M, Morelli P, Beghe B, Fabbri LM; AIFASMA Study Group. Regular versus as-needed budesonide and formoterol combination treatment for moderate asthma: a non-inferiority, randomised, double-blind clinical trial. Lancet Respir Med. 2015 Feb;3(2):109-119. doi: 10.1016/S2213-2600(14)70266-8. Epub 2014 Dec 4.