Clinical Trial of the Efficacy and Safety of Beclomethasone Dipropionate Plus Formoterol vs Fluticasone Propionate Plus Salmeterol in the 6 Months Step Down Treatment of Asthma (FORTE)

Study Description

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Brief Summary:

Asthma is a serious global health problem. People of all ages in countries throughout the world are affected by this chronic airway disorder that can be severe and sometimes fatal. The prevalence of asthma is increasing everywhere, especially among children.According to international guidelines, once control of asthma is achieved and maintained for at least 3 months, a gradual reduction of the maintenance therapy should be tried in order to identify the minimum therapy required to maintain control. This will help reduce the risk of side effects and enhance patient adherence to the treatment plan.

Reduction of therapy in patients on combination therapy should begin with a reduction in the dose of inhaled glucocorticosteroid.1 The present study is designed to evaluate if patients with controlled asthma treated with FP 1000 mcg + salmeterol 100 mcg daily can be stepped down. Stepping-down will be attempted with two medications: a new combination of extrafine beclomethasone dipropionate 400 mcg + formoterol 24 mcg daily (test medication, Foster™) and, alternatively, fluticasone propionate 500 mcg + salmeterol 100 mcg daily(reference medication) without losing asthma control.If this hypothesis will be confirmed, the present study will demonstrate that asthma control can be maintained with less than half the dose of inhaled corticosteroid and with less medical costs.

Given the aims of this study, the population to be monitored includes adult patients with moderate persistent asthma, which can be defined controlled according to the current guidelines under standard stabilised treatment. The intended treatment duration is therefore designed to ensure that good control of asthma is firmly achieved before stepping down the treatment (8 weeks run-in period), but also that the condition of the patients are followed long enough (24 weeks comparative treatment period) to ensure that a new stable condition is also obtained and properly monitored.

Condition or disease	Intervention/treatment	Phase
Asthma	Drug: Beclomethasone plus formoterol fixed combination; Drug: Fluticasone plus salmeterol fixed combination	Phase 3

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	382 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Prospective, Randomised, Open-label, Multicentre, Active Drug Controlled, Parallel Group Design Clinical Trial of the Efficacy and Safety of Beclomethasone Dipropionate 400 mcg + Formoterol 24 mcg pMDI Via HFA-134a (Foster™) vs. Fluticasone Propionate 500 mcg + Salmeterol Xinafoate 100 mcg DPI (Seretide Diskus®) in the 6 Months Stepdown Treatment of Adult Patients With Controlled Asthma
Study Start Date :	April 2007
Actual Primary Completion Date :	March 2010
Actual Study Completion Date :	March 2010

Arms and Interventions

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Arm	Intervention/treatment
Experimental: 1; Foster	Drug: Beclomethasone plus formoterol fixed combination; 100+6 pMDI
Active Comparator: 2; Seretide	Drug: Fluticasone plus salmeterol fixed combination; diskus 250/50

Outcome Measures

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Primary Outcome Measures :

1. Morning pre-dose PEF measured daily by patients (mean of the last 2 weeks of treatment period). [ Time Frame: mean of the last 2 weeks of treatment period ]

Secondary Outcome Measures :

1. symptom scores and symptom free days [ Time Frame: in the whole study period and every 2-week period ]
2. morning and evening pre-dose PEF and FEV1 measured daily by patients; [ Time Frame: daily and mean each 2-week period ]
3. pulmonary function tests measured at clinics (pre-dose PEF, FVC and FEV1); [ Time Frame: at aech clinic visit ]
4. change of FEV1 from pre-dose to 5, 15, 30 and 60 minutes post-dose; [ Time Frame: randomization visit and end of treatment visit ]
5. number, frequency and severity of exacerbations, time to first exacerbation [ Time Frame: whole study period ]
6. adverse events and adverse drug reactions [ Time Frame: retrospectively assessed at each visit ]
7. use of relief salbutamol and days without use of relief salbutamol; [ Time Frame: daily ]
8. proportion of patients with controlled asthma and partly controlled asthma, weeks of controlled asthma and partly controlled asthma; [ Time Frame: weekly ]
9. pharmaco-economic analysis of medical and non medical costs. [ Time Frame: during study period ]
10. 12 h-overnight urinary cortisol/creatinine [ Time Frame: (collected at visit 3, 6 and 9) ]
11. vital signs [ Time Frame: at each visit ]

Eligibility Criteria

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

Criteria

Inclusion Criteria:

• Patients will be enrolled for screening at Visit 1 into the run-in period if they meet all the following criteria:
• Clinical diagnosis of moderate persistent asthma for at least 6 months, according to GINA revised version 2005 guidelines 1 and considering current treatment;
• Forced expiratory volume (FEV1) or peak expiratory flow rate (PEFR) ≥ 80% of the predicted normal value;
• Treated with fluticasone 1000 mcg + salmeterol 100 mcg daily for at least 4 weeks at a stable dose;
• Reporting no nocturnal symptoms or awakenings, no exacerbations, no limitations of activities, symptoms in ≤2 days and use of rescue medication ≤2 days per week, in the last 4 weeks;
• Exhibiting a co-operative attitude and ability to be trained to correctly use the study devices and to complete the diary cards.

At the end of run in period (Week 8+0; Visit 3), patients will be recruited into the treatment period and randomized to treatment if they meet the following criterion:

• Asthma is controlled 1 in each of the last 4 weeks of run-in (no nocturnal symptoms or awakenings; no exacerbations; no limitations of activities; symptoms in ≤2 days; use of rescue medication ≤2 days; morning PEF ≥80% of predicted in every day) confirmed by reviewing the diary cards.

Exclusion Criteria:

• Inability to carry out pulmonary function testing;
• Diagnosis of Chronic Obstructive Pulmonary Disease (COPD) as defined by the NHLBI/WHO's GOLD guidelines;
• Current smokers or recent (less than one year) ex-smokers with a smoking history of ≥10 pack/years;
• History of near fatal asthma;
• Evidence of symptomatic infection of the airways in the previous 8 weeks;
• Three or more courses of oral corticosteroids or hospitalisation due to asthma during the previous 6 months;
• Patients treated with anticholinergics and antihistamines during the previous 2 weeks, with topical or intranasal corticosteroids and leukotriene antagonists during the previous 4 weeks;
• History or current evidence of heart failure, coronary artery disease, myocardial infarction, severe hypertension, cardiac arrhythmias;
• Diabetes mellitus;
• PTCA or CABG during the previous six months;
• Patients with an abnormal QTc interval value in the ECG test, defined as >450 msec in males or > 470 msec in females;
• Other haemodynamic relevant rhythm disturbances (including atrial flutter or atrial fibrillation with ventricular response, bradycardia (≤55 bpm), evidence of atrial-ventricular (AV) block on ECG of more than 1st degree;
• Clinically significant or unstable concurrent diseases: uncontrolled hyperthyroidism, significant hepatic impairment, poorly controlled pulmonary (tuberculosis, active mycotic infection of the lung), gastrointestinal (e.g. active peptic ulcer), neurological or haematological autoimmune diseases;
• Cancer or any chronic diseases with prognosis <2 years;
• 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 who received any investigational new drug within the last 12 weeks;

At the end of run in period (Week 8+0; Visit 3), patients will not be randomized to treatment if they do not completely meet the definition of "controlled asthma". These subjects will be considered screening failures and will not count against the planned number to be recruited.

Contacts and Locations

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Locations

Bulgaria
Clinic of Pulmonology, UMHAT "Sveti Georgi"
Plovdiv, Bulgaria, 4002
First Department of Pulmonology, Regional Dispensery of Pulmonology and Phtisiatric Diseases with Stationary (RDPPDS)
Ruse, Bulgaria, 7002
Clinic of Pulmonology, University Hospital "Lozenetz"
Sofia, Bulgaria
First Internal Clinic, Endocrinology and Pulmonology Department MHAT
Stara Zagora, Bulgaria, 6000
Italy
U.O.C. S.Anna e S. Sebastiano - Malattie dell'apparato respiratorio
Caserta, Italy
Ospedale S. Camillo de Lellis - U.O.C. Pneumologia
Chieti, Italy
Ospedale Cardarelli - Fisiopatologia Respiratoria
Napoli, Italy
CNR - Dipartimento di Fisiopatologia Respiratoria
Palermo, Italy
Ukraine
Department of Hospital Pediatrics Crimean State Medical University. Pulmonology Department of Republican Clinical Children's Hospital
Crimea, Ukraine, 95004
Pulmonological Department #2
Kharkiv, Ukraine, 61035
Pulmonological Department of the Institute of Therapy, Ukrainian Academy of Medical Sciences
Kharkiv, Ukraine, 61035
Pulmonological and Allergological Department of the Kharkov Regional Clinical Hospital
Kharkov, Ukraine, 61022
Department of General Practice- Family medicine. Medical Academy of postgraduate education.
Kharkov, Ukraine
Department of Diagnostic, Therapy and Clinical Pharmacology of Lung Diseases of the Institute of Phthisiology and Pulmonology Academy of Medical Science of the Ukraine
Kiev, Ukraine, 03680
Institute of pthysiology and pulmonology Academy of medical science of the Ukraine.
Kiev, Ukraine, 03680
Pulmonology Department of the Institute of Phthisiology and Pulmonology AMS of the Ukraine
Kiev, Ukraine, 03680
Clinical Hospital 8, Department of pediatrics and clinical laboratories
Kriviy Rig, Ukraine
Department of Hospital Therapy of Lugansk State Medical Institute. Lugansk Regional Clinical Hospital
Lugansk, Ukraine, 91045

Sponsors and Collaborators

Chiesi Farmaceutici S.p.A.

Investigators

Principal Investigator:	Pierluigi Paggiaro, MD	Ospedale Cisanello, Pisa

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Additional Information:

Study Record on EU Clinical Trials Register including results 

Publications of Results:

Papi A, Nicolini G, Crimi N, Fabbri L, Olivieri D, Rossi A, Paggiaro P. Step-down from high dose fixed combination therapy in asthma patients: a randomized controlled trial. Respir Res. 2012 Jun 25;13:54. doi: 10.1186/1465-9921-13-54.

Responsible Party:	Gabriele Nicolini, Chiesi Farmaceutici
ClinicalTrials.gov Identifier:	NCT00497237 History of Changes
Other Study ID Numbers:	MC/PR/033011/005/06; 2006-005349-13 ( EudraCT Number )
First Posted:	July 6, 2007
Last Update Posted:	March 30, 2017
Last Verified:	March 2017

Keywords provided by Chiesi Farmaceutici S.p.A.:

Asthma; Stepdown; Beclomethasone; Formoterol; Corticosteroids

Additional relevant MeSH terms:

Asthma; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Fluticasone; Beclomethasone; Formoterol Fumarate; Salmeterol Xinafoate; Anti-Inflammatory Agents; Bronchodilator Agents	Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Asthmatic Agents; Respiratory System Agents; Dermatologic Agents; Anti-Allergic Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Adrenergic Agonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Glucocorticoids; Hormones