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

Asthma Clinical Trial

Official title:

As Needed Budesonide/Formoterol Combination Versus Regular Budesonide/Formoterol Combination Plus as Needed Terbutaline in Mild-Moderate Persistent Asthma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00849095
• Other study ID #: AIFA-ASMA-BF-001
• Secondary ID: EudraCT number:
• Status: Completed
• Phase: Phase 3
• First received: February 20, 2009
• Last updated: May 29, 2014
• Start date: April 2009
• Est. completion date: May 2013

Study information

• Verified date: May 2014
• Source: Università degli Studi di Ferrara
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: The Italian Medicines Agency
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 860
• Est. completion date: May 2013
• Est. primary completion date: April 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Asthma

Intervention

Drug:
• budesonide/formoterol combination (PRN)
budesonide/formoterol combination 160/4.5 mcg 1 inhalation used as needed for a period of 52 weeks
• budesonide/formoterol combination
budesonide/formoterol 160/4.5 mcg 1 inhalation bid
• placebo
bid inhaled placebo
• terbutaline
as needed terbutaline 500 mcg for a period of 52 weeks

Locations

Country	Name	City	State
Italy	Ospedale regionale Umberto I, Unità Operativa di Allergologia	Ancona	AN
Italy	Dipartimento di Scienze Mediche-Unità Operativa di Pneumologia	Benevento	BN
Italy	Policlinico Sant'Orsola Malpighi, Unità Operativa di Pneumologia	Bologna	BO
Italy	Servizio Pneumologico ASL Brindisi	Brindisi
Italy	Ospedale di Bussolengo, Unità operativa di Pneumologia	Bussolengo	VR
Italy	Fondazione S. Maugeri - IRCCS -dipartimento di Pneumologia riabilitativa	Cassano delle Murge	BA
Italy	Università degli Studi di Catania, Unità operativa di Pneumologia	Catania	CT
Italy	Università Magna Grecia Catanzaro, unità operativa di Pneumologia	Catanzaro	CZ
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	Ospedale Morgagni Pierantoni, azienda Ospedaliera di Forlì, Unitaà operativa di Pneumologia	Forlì	FC
Italy	Ospadale San Carlo Borromeo - Unità operativa di Pneumologia	Milano	MI
Italy	Università di Modena e Reggio Emilia, Unità operativa di Pneumologia	Modena	MO
Italy	Seconda Università degli stuidi di Napoli, unità Operativa di Pneumologia	Napoli
Italy	Università degli studi di Padova, dipartimento di Pneunmologia	Padova	PD
Italy	Università degli studi di Padova, Medicina del Lavoro	Padova	PD
Italy	Università degli Studi di Palermo, Ospedale "V. Cervello"	Palermo	Pa
Italy	Giuseppina Bertorelli	Parma
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 degli studi di Pisa, Ospedale Cisanello, unità operativa di Pneumologia	Pisa	PI
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 di Roma Tor Vergata, unità di malattie dell'apparato Respiratorio	Roma
Italy	Università Roma La Sapienza, servizio di Fisiopatologia respiratoria	Roma	RM
Italy	Ospedale città di Sesto San Giovanni, Unità operativa di Pneumologia	Sesto San Giovanni	MI
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	azienda universitaria-ospedaliera istituti ospitalieri di Verona, unità operativa di Allergologia	Verona	VR

Sponsors (1)

Lead Sponsor	Collaborator
Università degli Studi di Ferrara

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	comparison between groups of the relative risk for treatment failure		52 weeks	Yes
Secondary	number of treatment failures		52 weeks	Yes
Secondary	time to first treatment failure		52 weeks	Yes
Secondary	differences between groups of lung function parameters, quality of life, symptoms score, use of as needed medication, adverse events		52 weeks	Yes