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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00849095
Recruitment Status : Completed
First Posted : February 23, 2009
Last Update Posted : May 30, 2014
Information provided by (Responsible Party):
Alberto Papi, MD, Università degli Studi di Ferrara

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).

Condition or disease Intervention/treatment Phase
Asthma Drug: budesonide/formoterol combination (PRN) Drug: budesonide/formoterol combination Drug: placebo Drug: terbutaline Phase 3

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 860 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: As Needed Budesonide/Formoterol Combination Versus Regular Budesonide/Formoterol Combination Plus as Needed Terbutaline in Mild-Moderate Persistent Asthma
Study Start Date : April 2009
Actual Primary Completion Date : April 2013
Actual Study Completion Date : May 2013

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Asthma
U.S. FDA Resources

Arm Intervention/treatment
Experimental: as needed medication
patients assigned to this arm will take bid inhaled placebo plus prn inhaled 160/4.5 mcg budesonide/formoterol combination
Drug: budesonide/formoterol combination (PRN)
budesonide/formoterol combination 160/4.5 mcg 1 inhalation used as needed for a period of 52 weeks
Other Name: budesonide/formoterol combination
Drug: placebo
bid inhaled placebo
Active Comparator: guideline treatment
bid inhaled 160/4.5 mcg budesonide/formoterol combination plus prn 500 mcg terbutaline
Drug: budesonide/formoterol combination
budesonide/formoterol 160/4.5 mcg 1 inhalation bid
Drug: terbutaline
as needed terbutaline 500 mcg for a period of 52 weeks

Primary Outcome Measures :
  1. comparison between groups of the relative risk for treatment failure [ Time Frame: 52 weeks ]

Secondary Outcome Measures :
  1. number of treatment failures [ Time Frame: 52 weeks ]
  2. time to first treatment failure [ Time Frame: 52 weeks ]
  3. differences between groups of lung function parameters, quality of life, symptoms score, use of as needed medication, adverse events [ Time Frame: 52 weeks ]

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Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00849095

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, 82100
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
Ferrara, FE, Italy, 44100
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
Milano, 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
Università degli Studi di Palermo, Ospedale "V. Cervello"
Palermo, Pa, Italy, 90146
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 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
Giuseppina Bertorelli
Parma, Italy, 43100
Università di Roma Tor Vergata, unità di malattie dell'apparato Respiratorio
Roma, Italy
Sponsors and Collaborators
Università degli Studi di Ferrara
Principal Investigator: Alberto Papi, MD Università degli Studi di Ferrara

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Alberto Papi, MD, Professor, Università degli Studi di Ferrara Identifier: NCT00849095     History of Changes
Other Study ID Numbers: AIFA-ASMA-BF-001
EudraCT number: 2008-004127-36 ( Registry Identifier: NCT00849095 )
First Posted: February 23, 2009    Key Record Dates
Last Update Posted: May 30, 2014
Last Verified: May 2014

Keywords provided by Alberto Papi, MD, Università degli Studi di Ferrara:
Bronchodilator Agents
Double-Blind Method
Drug Therapy, Combination
Forced Expiratory Volume

Additional relevant MeSH terms:
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Immune System Diseases
Formoterol Fumarate
Budesonide, Formoterol Fumarate Drug Combination
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Anti-Inflammatory Agents
Hormones, Hormone Substitutes, and Hormone Antagonists