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

NCT ID: NCT00849095

Last Updated: 2014-05-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 860 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-04-30
• Study Completion Date: 2013-05-31

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.

Conditions

Asthma

Keywords

Adult; Asthma; Bronchodilator Agents; Budesonide; Double-Blind Method; Drug Therapy, Combination; Ethanolamines; Female; Forced Expiratory Volume; Humans; Male; Terbutaline

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

as needed medication

patients assigned to this arm will take bid inhaled placebo plus prn inhaled 160/4.5 mcg budesonide/formoterol combination

Group Type: EXPERIMENTAL

budesonide/formoterol combination (PRN)

Intervention Type: DRUG

budesonide/formoterol combination 160/4.5 mcg 1 inhalation used as needed for a period of 52 weeks

placebo

Intervention Type: DRUG

bid inhaled placebo

guideline treatment

bid inhaled 160/4.5 mcg budesonide/formoterol combination plus prn 500 mcg terbutaline

Group Type: ACTIVE_COMPARATOR

budesonide/formoterol combination

Intervention Type: DRUG

budesonide/formoterol 160/4.5 mcg 1 inhalation bid

terbutaline

Intervention Type: DRUG

as needed terbutaline 500 mcg for a period of 52 weeks

Interventions

budesonide/formoterol combination (PRN)

budesonide/formoterol combination 160/4.5 mcg 1 inhalation used as needed for a period of 52 weeks

Intervention Type: DRUG

budesonide/formoterol combination

budesonide/formoterol 160/4.5 mcg 1 inhalation bid

Intervention Type: DRUG

placebo

bid inhaled placebo

Intervention Type: DRUG

terbutaline

as needed terbutaline 500 mcg for a period of 52 weeks

Intervention Type: DRUG

Other Intervention Names

budesonide/formoterol combination

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Università degli Studi di Ferrara

OTHER

Sponsor Role: lead

Responsible Party

Alberto Papi, MD

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Alberto Papi, MD

Role: PRINCIPAL_INVESTIGATOR

Università degli Studi di Ferrara

Locations

Ospedale regionale Umberto I, Unità Operativa di Allergologia

Ancona, AN, Italy

Fondazione S. Maugeri - IRCCS -dipartimento di Pneumologia riabilitativa

Cassano delle Murge, BA, Italy

Dipartimento di Scienze Mediche-Unità Operativa di Pneumologia

Benevento, BN, Italy

Policlinico Sant'Orsola Malpighi, Unità Operativa di Pneumologia

Bologna, BO, Italy

Università degli Studi di Catania, Unità operativa di Pneumologia

Catania, CT, Italy

Università Magna Grecia Catanzaro, unità operativa di Pneumologia

Catanzaro, CZ, Italy

Ospedale Morgagni Pierantoni, azienda Ospedaliera di Forlì, Unitaà operativa di Pneumologia

Forlì, FC, Italy

UNIVERSITà DEGLI STUDI DI FERRARA, CLINICA DI MALATTIE DELL'APPARATO RESPIRATORIO

Ferrara, FE, Italy

Università degli studi di Foggia, ospedale pneumologico D'Avanzo, unità operativa di malattie dell'apparato respiratorio

Foggia, FG, Italy

Ospadale San Carlo Borromeo - Unità operativa di Pneumologia

Milan, MI, Italy

Ospedale città di Sesto San Giovanni, Unità operativa di Pneumologia

Sesto San Giovanni, MI, Italy

Università di Modena e Reggio Emilia, Unità operativa di Pneumologia

Modena, MO, Italy

Giuseppina Bertorelli

Parma, Parma, Italy

Università degli Studi di Palermo, Ospedale "V. Cervello"

Palermo, Pa, Italy

Università degli studi di Padova, dipartimento di Pneunmologia

Padua, PD, Italy

Università degli studi di Padova, Medicina del Lavoro

Padua, PD, Italy

Università degli studi di Pisa, Ospedale Cisanello, unità operativa di Pneumologia

Pisa, PI, Italy

Università degli stiudi di Parma, unità operativa di Pneumologia

Parma, PR, Italy

IRCCS Fondazione S Maugeri, Dipartimento di Allergologia

Pavia, PV, Italy

Università degli studi di Pavia, dipartimento di Pneumologia

Pavia, PV, Italy

università Cattolica del Sacro Cuore, Columbus, unità operativa di allergologia

Roma, RM, Italy

Università Cattolica del Sacro Cuore, Policlinico Gemelli, unità operativa di Pneumologia

Roma, RM, Italy

Università Roma La Sapienza, servizio di Fisiopatologia respiratoria

Roma, RM, Italy

Università di Perugia -Terni, Medcina del lavoro Terni

Terni, TI, Italy

Università degli studi di Torino, Dipartimento di scienze biomediche ed oncologia umana

Torino, TO, Italy

Ospedale di Cattinara, unità operativa di pneumologia

Trieste, TS, Italy

Ospedale di Bussolengo, Unità operativa di Pneumologia

Bussolengo, VR, Italy

azienda universitaria-ospedaliera istituti ospitalieri di Verona, unità operativa di Allergologia

Verona, VR, Italy

Servizio Pneumologico ASL Brindisi

Brindisi, , Italy

Seconda Università degli stuidi di Napoli, unità Operativa di Pneumologia

Napoli, , Italy

Università di Roma Tor Vergata, unità di malattie dell'apparato Respiratorio

Roma, , Italy

Countries

Italy

References

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.

Reference Type: DERIVED

PMID: 25481378 (View on PubMed)

Other Identifiers

EudraCT number: 2008-004127-36

Identifier Type: REGISTRY

Identifier Source: secondary_id

AIFA-ASMA-BF-001

Identifier Type: -

Identifier Source: org_study_id