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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)
This study is currently recruiting participants.
Verified by Chiesi Farmaceutici S.p.A., January 2009
First Received: July 4, 2007   Last Updated: January 20, 2009   History of Changes
Sponsor: Chiesi Farmaceutici S.p.A.
Information provided by: Chiesi Farmaceutici S.p.A.
ClinicalTrials.gov Identifier: NCT00497237
  Purpose

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 Intervention Phase
Asthma
Drug: Beclomethasone plus formoterol fixed combination
Drug: Fluticasone plus salmeterol fixed combination
Phase III

Study Type: Interventional
Study Design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study
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

Resource links provided by NLM:


Further study details as provided by Chiesi Farmaceutici S.p.A.:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • symptom scores and symptom free days [ Time Frame: in the whole study period and every 2-week period ] [ Designated as safety issue: No ]
  • morning and evening pre-dose PEF and FEV1 measured daily by patients; [ Time Frame: daily and mean each 2-week period ] [ Designated as safety issue: No ]
  • pulmonary function tests measured at clinics (pre-dose PEF, FVC and FEV1); [ Time Frame: at aech clinic visit ] [ Designated as safety issue: No ]
  • change of FEV1 from pre-dose to 5, 15, 30 and 60 minutes post-dose; [ Time Frame: randomization visit and end of treatment visit ] [ Designated as safety issue: No ]
  • number, frequency and severity of exacerbations, time to first exacerbation [ Time Frame: whole study period ] [ Designated as safety issue: No ]
  • adverse events and adverse drug reactions [ Time Frame: retrospectively assessed at each visit ] [ Designated as safety issue: Yes ]
  • use of relief salbutamol and days without use of relief salbutamol; [ Time Frame: daily ] [ Designated as safety issue: No ]
  • proportion of patients with controlled asthma and partly controlled asthma, weeks of controlled asthma and partly controlled asthma; [ Time Frame: weekly ] [ Designated as safety issue: No ]
  • pharmaco-economic analysis of medical and non medical costs. [ Time Frame: during study period ] [ Designated as safety issue: No ]
  • 12 h-overnight urinary cortisol/creatinine [ Time Frame: (collected at visit 3, 6 and 9) ] [ Designated as safety issue: Yes ]
  • vital signs [ Time Frame: at each visit ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 382
Study Start Date: April 2007
Estimated Study Completion Date: July 2010
Estimated Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
1: Experimental
Foster
Drug: Beclomethasone plus formoterol fixed combination
100+6 pMDI
2: Active Comparator
Seretide
Drug: Fluticasone plus salmeterol fixed combination
diskus 250/50

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00497237

Contacts
Contact: Pierluigi Paggiaro, MD 050995366

Locations
Bulgaria
Clinic of Pulmonology, University Hospital "Lozenetz" Not yet recruiting
Sofia, Bulgaria
Contact: Georgi Hinkov, Dr.     00359 2 960 7557     drhinkov@abv.bg    
Clinic of Pulmonology, UMHAT "Sveti Georgi" Not yet recruiting
Plovdiv, Bulgaria, 4002
Contact: Vladimir Hodzhev, Prof     0035932 602990     vahodgev@abv.bg    
First Internal Clinic, Endocrinology and Pulmonology Department MHAT Not yet recruiting
Stara Zagora, Bulgaria, 6000
Contact: Dimo Mitev Dimov, Dr     00359 42 66 44 93     dmdimov@yahoo.com    
First Department of Pulmonology, Regional Dispensery of Pulmonology and Phtisiatric Diseases with Stationary (RDPPDS) Not yet recruiting
Ruse, Bulgaria, 7002
Contact: Hristo Metev, Dr     00359 82 82 38 79     h_metev_2003@yahoo.com    
Italy
CNR - Dipartimento di Fisiopatologia Respiratoria Recruiting
Palermo, Italy
Principal Investigator: Mark Gjomarkaj, MD            
Ospedale S. Camillo de Lellis - U.O.C. Pneumologia Recruiting
Chieti, Italy
Principal Investigator: Fernando De Benedetto, MD            
Ospedale Cardarelli - Fisiopatologia Respiratoria Recruiting
Napoli, Italy
Principal Investigator: Fausto De Michele, MD            
U.O.C. S.Anna e S. Sebastiano - Malattie dell'apparato respiratorio Recruiting
Caserta, Italy
Contact: , MD            
Principal Investigator: Riccardo Cioffi, MD            
Ukraine
Pulmonological Department of the Institute of Therapy, Ukrainian Academy of Medical Sciences Not yet recruiting
Kharkiv, Ukraine, 61035
Contact: Yefimov Volodymyr, Dr.     +38 057 775 15 51     igs@therapy.ac.kharkov.ua    
Clinical Hospital 8, Department of pediatrics and clinical laboratories Not yet recruiting
Kriviy Rig, Ukraine
Contact: Svitlana Mokia-Serbina, Prof.     +380564365303     litvinova_2008@ukr.net    
Department of Diagnostic, Therapy and Clinical Pharmacology of Lung Diseases of the Institute of Phthisiology and Pulmonology Academy of Medical Science of the Ukraine Not yet recruiting
Kiev, Ukraine, 03680
Contact: Lyudmyla Yashyna, Prof.     +38 044 275 0568     diagnost@ifp.kiev.ua    
Institute of pthysiology and pulmonology Academy of medical science of the Ukraine. Not yet recruiting
Kiev, Ukraine, 03680
Contact: Viktoria Kostromina, Prof.     +38 044 275 3602     child@ifp.kiev.ua    
Department of Hospital Therapy of Lugansk State Medical Institute. Lugansk Regional Clinical Hospital Not yet recruiting
Lugansk, Ukraine, 91045
Contact: Olena Olenitskaya, Dr.     +380642580979        
Department of General Practice- Family medicine. Medical Academy of postgraduate education. Not yet recruiting
Kharkov, Ukraine
Contact: Olexiy Korzh, Prof.     + 38 057 738 70 18     alexeykorzh@mail.ru    
Pulmonological Department #2 Not yet recruiting
Kharkiv, Ukraine, 61035
Contact: Dr. Viktor Blazhko     +38 057 721 09 48     blazhkopulm@mail.ru    
Department of Hospital Pediatrics Crimean State Medical University. Pulmonology Department of Republican Clinical Children's Hospital Not yet recruiting
Crimea, Ukraine, 95004
Contact: T. Kobets, Prof.     + 38 0652 25 34 26     kobez@yandex.ru    
Pulmonological and Allergological Department of the Kharkov Regional Clinical Hospital Not yet recruiting
Kharkov, Ukraine, 61022
Contact: Z. Semydotska, Prof.     +38 057 705 0209     vade_mecum2001@yahoo.com    
Pulmonology Department of the Institute of Phthisiology and Pulmonology AMS of the Ukraine Not yet recruiting
Kiev, Ukraine, 03680
Contact: Feshchenko Yuriy, Prof.     +380442750402     admin@ifp.kiev.ua    
Sponsors and Collaborators
Chiesi Farmaceutici S.p.A.
Investigators
Principal Investigator: Pierluigi Paggiaro, MD Ospedale Cisanello, Pisa
  More Information

No publications provided

Responsible Party: Chiesi Farmaceutici ( Gabriele Nicolini )
Study ID Numbers: MC/PR/033011/005/06
Study First Received: July 4, 2007
Last Updated: January 20, 2009
ClinicalTrials.gov Identifier: NCT00497237     History of Changes
Health Authority: Italy: Ministry of Health;   Bulgaria: Ministry of Health;   Spain: Ministry of Health and Consumption;   Ukraine: Ministry of Health

Keywords provided by Chiesi Farmaceutici S.p.A.:
Asthma
Stepdown
Beclomethasone
Formoterol
Corticosteroids

Additional relevant MeSH terms:
Anti-Inflammatory Agents
Respiratory System Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Bronchial Diseases
Adrenergic Agents
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Beclomethasone
Hormones
Adrenergic Agonists
Hypersensitivity
Lung Diseases, Obstructive
Respiratory Tract Diseases
Therapeutic Uses
Formoterol
Fluticasone
Dermatologic Agents
Salmeterol
Immune System Diseases
Adrenergic beta-Agonists
Asthma
Anti-Asthmatic Agents
Anti-Allergic Agents
Glucocorticoids
Pharmacologic Actions
Autonomic Agents
Lung Diseases
Hypersensitivity, Immediate
Peripheral Nervous System Agents

ClinicalTrials.gov processed this record on February 08, 2010