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

Sponsor:	Università degli Studi di Ferrara
Information provided by:	Università degli Studi di Ferrara
ClinicalTrials.gov Identifier:	NCT00849095

Purpose

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	Intervention	Phase
Asthma	Drug: budesonide/formoterol combination (PRN) Drug: budesonide/formoterol combination Drug: placebo Drug: terbutaline	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:

MedlinePlus related topics: Asthma

Drug Information available for: Terbutaline Terbutaline sulfate Formoterol fumarate Budesonide Formoterol Arformoterol Tartrate

U.S. FDA Resources

Further study details as provided by Università degli Studi di Ferrara:

Primary Outcome Measures:

comparison between groups of the relative risk for treatment failure [ Time Frame: 52 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

number of treatment failures and of drop-out [ Time Frame: 52 weeks ] [ Designated as safety issue: Yes ]
time to first treatment failure and to drop-out [ Time Frame: 52 weeks ] [ Designated as safety issue: Yes ]
differences between groups of lung function parameters, quality of life, symptoms score, use of as needed medication, adverse events [ Time Frame: 52 weeks ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	960
Study Start Date:	April 2009
Estimated Study Completion Date:	October 2011
Estimated Primary Completion Date:	January 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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 Other Name: 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 Other Name: budesonide/formoterol combination Drug: terbutaline as needed terbutaline 500 mcg for a period of 52 weeks Other Name: terbutaline

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

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00849095

Contacts

Contact: Alberto Papi, MD	+390532210420	ppa@unife.it
Contact: Brunilda Marku, MD	+390532236908	brunilda74@hotmail.com

Locations

Italy
Ospedale regionale Umberto I, Unità Operativa di Allergologia	Recruiting
Ancona, AN, Italy
Contact: Floriano Bonifazi, MD +390715963251 f.bonifazi@ao-umbertoprimo.marche.it
Fondazione S. Maugeri - IRCCS -dipartimento di Pneumologia riabilitativa	Recruiting
Cassano delle Murge, BA, Italy
Contact: Antonio Spanevello, MD +390807814111 aspanevello@quisoft.it
Dipartimento di Scienze Mediche-Unità Operativa di Pneumologia	Not yet recruiting
Benevento, BN, Italy, 82100
Contact: Mario del Donno, MD 0824.57751 m.deldonno@ao.rummo.it
Policlinico Sant'Orsola Malpighi, Unità Operativa di Pneumologia	Recruiting
Bologna, BO, Italy
Contact: Mario Schiavina, MD +390516363111 mario.schiavina@aosp.bo.it
Università degli Studi di Catania, Unità operativa di Pneumologia	Recruiting
Catania, CT, Italy
Contact: Nunzio Crimi, MD +390957593535 crimi@unict.it
Università Magna Grecia Catanzaro, unità operativa di Pneumologia	Recruiting
Catanzaro, CZ, Italy
Contact: Rosario Maselli, MD +3909613647171 rmaselli@unicz.it
Ospedale Morgagni Pierantoni, azienda Ospedaliera di Forlì, Unitaà operativa di Pneumologia	Recruiting
Forlì, FC, Italy
Contact: Fiorino Fiorentini, MD +39054376123 ffiorent@ausl.fo.it
UNIVERSITà DEGLI STUDI DI FERRARA, CLINICA DI MALATTIE DELL'APPARATO RESPIRATORIO	Recruiting
Ferrara, FE, Italy, 44100
Contact: Alberto Papi, MD +390532210420 ppa@unife.it
Sub-Investigator: Alessandro Zanforlin, MD
Sub-Investigator: Brunilda Marku, MD
Università degli studi di Foggia, ospedale pneumologico D'Avanzo, unità operativa di malattie dell'apparato respiratorio	Recruiting
Foggia, FG, Italy
Contact: Maria Pia Foschino, MD +390881617832 mfoschino@qubisoft.it
Università degli studi di Genova, Unità operativa di Pneumologia	Recruiting
Genova, GE, Italy
Contact: Giorgio W Canonica, MD +3901035385933 canonica@unige.it
Ospadale San Carlo Borromeo - Unità operativa di Pneumologia	Suspended
Milano, MI, Italy
Ospedale città di Sesto San Giovanni, Unità operativa di Pneumologia	Recruiting
Sesto San Giovanni, MI, Italy
Contact: Antonio Foresi, MD +390226257356 antonio.foresi@aovimercate.org
Università di Modena e Reggio Emilia, Unità operativa di Pneumologia	Recruiting
Modena, MO, Italy
Contact: Leonardo M Fabbri, MD +390594222198 fabbri.leonardo@unimore.it
Università degli Studi di Palermo, Ospedale "V. Cervello"	Recruiting
Palermo, Pa, Italy, 90146
Contact: Nicola Scichilone, MD, PHD 0916802652 n.scichilone@libero.it
Università degli studi di Padova, dipartimento di Pneunmologia	Recruiting
Padova, PD, Italy
Contact: Marina Saetta, MD +390498213732 marina.saetta@unipd.it
Università degli studi di Padova, Medicina del Lavoro	Recruiting
Padova, PD, Italy
Contact: Piero Maestrelli, MD +390498212564 piero.maestrelli@unipd.it
Università degli studi di Pisa, Ospedale Cisanello, unità operativa di Pneumologia	Recruiting
Pisa, PI, Italy
Contact: Pierluigi Paggiaro, MD +39050995266 ppaggiaro@qubisoft.it
Università degli stiudi di Parma, unità operativa di Pneumologia	Recruiting
Parma, PR, Italy
Contact: Dario Olivieri, MD +390521290577 olivieri@unipr.it
IRCCS Fondazione S Maugeri, Dipartimento di Allergologia	Recruiting
Pavia, PV, Italy
Contact: Gianna Moscato, MD +390382592941 moscato@fsm.it
Università degli studi di Pavia, dipartimento di Pneumologia	Recruiting
Pavia, PV, Italy
Contact: Ernesto Pozzi, MD +390382422232 ernesto.pozzi@unipv.it
Università Roma La Sapienza, servizio di Fisiopatologia respiratoria	Recruiting
Roma, RM, Italy
Contact: Paolo Palange, MD +390649972082 paolo.palange@uniroma1.it
università Cattolica del Sacro Cuore, Columbus, unità operativa di allergologia	Recruiting
Roma, RM, Italy
Contact: Antonino Romano, MD +39063503782 romano@rm.unicatt.it
Università Cattolica del Sacro Cuore, Policlinico Gemelli, unità operativa di Pneumologia	Recruiting
Roma, RM, Italy
Contact: Salvatore Valente, MD +390630154335 svalente@rm.unicatt.it
Ospadale di Cava de' Tirreni, Unità operativa di Fisiopatologia Respiratoria	Not yet recruiting
Cava de' Tirreni, SA, Italy
Contact: Mario Polverino, MD +390894455365 mpolverino@qubisoft.it
Università di Perugia -Terni, Medcina del lavoro Terni	Recruiting
Terni, TI, Italy
Contact: Andrea Siracusa, MD +390744205554 asiracus@unipg.it
Università degli studi di Torino, Dipartimento di scienze biomediche ed oncologia umana	Recruiting
Torino, TO, Italy
Contact: Caterina Bucca, MD +390116336748 caterina.bucca@unito.it
Ospedale di Cattinara, unità operativa di pneumologia	Recruiting
Trieste, TS, Italy
Contact: Marco Confalonieri, MD +390403993136 marco.confalonieri@aots.sanita.fvg.it
Ospedale di Bussolengo, Unità operativa di Pneumologia	Recruiting
Bussolengo, VR, Italy
Contact: Roberto W Dal Negro, MD +390456712193 rdalnegro@ulss22.ven.it
azienda universitaria-ospedaliera istituti ospitalieri di Verona, unità operativa di Allergologia	Recruiting
Verona, VR, Italy
Contact: Gianenrico Senna, MD +390458122347 gianenrico.senna@mail.azosp.vr.it
Servizio Pneumologico ASL Brindisi	Recruiting
Brindisi, Italy
Contact: Eugenio Sabato, MD +390831.536525 esabato@qubisoft.it
Seconda Università degli stuidi di Napoli, unità Operativa di Pneumologia	Recruiting
Napoli, Italy
Contact: Antonio S Marsico, MD +390815453017 serafino.marsico@unina2.it
Università di Roma Tor Vergata, unità di malattie dell'apparato Respiratorio	Not yet recruiting
Roma, Italy
Contact: Mario Cazzola, MD +390655170461 mario.cazzola@uniroma2.it

Sponsors and Collaborators

Università degli Studi di Ferrara

Investigators

Principal Investigator:

Alberto Papi, MD

Università degli Studi di Ferrara

More Information

No publications provided

Responsible Party:	Alberto Papi, Universitaria di Ferrara
ClinicalTrials.gov Identifier:	NCT00849095 History of Changes
Other Study ID Numbers:	AIFA-ASMA-BF-001, EudraCT number: 2008-004127-36
Study First Received:	February 20, 2009
Last Updated:	October 8, 2010
Health Authority:	Italy: The Italian Medicines Agency

Keywords provided by Università degli Studi di Ferrara:

Adult
Asthma
Bronchodilator Agents
Budesonide
Double-Blind Method
Drug Therapy, Combination

Ethanolamines
Female
Forced Expiratory Volume
Humans
Male
Terbutaline

Additional relevant MeSH terms:

Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Bronchodilator Agents
Terbutaline
Budesonide
Formoterol
Symbicort
Autonomic Agents

Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Sympathomimetics
Tocolytic Agents
Reproductive Control Agents
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 24, 2012