Symptom-driven Maintenance and Reliever Treatment to Prevent Exacerbations in COPD

Sponsor

University Medical Center Groningen (Other)

Overall Status

Unknown status

CT.gov ID

NCT02477397

Collaborator

(none)

201

Enrollment

Location

Arms

55.5

Anticipated Duration (Months)

3.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Study to investigate the effects of symptom-driven maintenance and reliever therapy in COPD.

Condition or Disease	Intervention/Treatment	Phase
COPD	Drug: Spiromax Budesonide/formoterol Drug: Diskus Fluticasone/salmeterol	Phase 3

Detailed Description

Rationale: Chronic obstructive pulmonary disease (COPD) is a leading cause of death worldwide and its morbidity and mortality are still rising. A symptom-driven maintenance and reliever therapy (SMART) with budesonide/formoterol is a frequently used treatment strategy in asthma. Several studies have shown that the SMART approach effectively reduces the number of asthma exacerbations when compared to a fixed maintenance dose of, e.g. fluticasone/salmeterol. In addition, larger improvements in lung function and symptoms have been observed in asthma patients with the SMART approach. Thus far, no studies have investigated the efficacy of the SMART approach in patients with COPD. The investigators hypothesize that SMART treatment with budesonide/formoterol will be more effective than fluticasone/salmeterol fixed dose treatment in COPD.

Objective: This research proposal aims to investigate the efficacy of the SMART approach with budesonide/fomoterol versus fixed dose treatment with fluticasone/salmeterol in patients with COPD.

Study design: This will be a randomized, parallel 2-arm, open-label, multi-centre study.

Study population: A total of 260 COPD patients will be included with a smoking history of >10 pack years, an FEV1 <80% predicted either or not using inhaled corticosteroids and having had at least one COPD exacerbation during the 2 years prior to inclusion.

Intervention: COPD patients will be randomized to one of the following two treatment groups:

A: One year Spiromax® budesonide/formoterol 160/4.5 μg two inhalations twice daily + Spiromax® budesonide/formoterol 160/4.5 μg as needed with a maximum of 8 inhalations daily.

B: One year Diskus® fluticasone/salmeterol 500/50 μg one inhalation twice daily + salbutamol 100 μg as needed with a maximum of 8 inhalations daily.

Main study endpoints/objectives: The primary endpoint is the reduction in number of COPD exacerbations requiring treatment with oral prednisolone).

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: This study has no specific benefits for the participating patients. The study also has no major risks. Minor risks for participants in this study are:

Nasal epithelium collection may cause a temporary nose bleed.
Blood collection may cause bruising.
All drugs may cause side effects. The combination treatments with an inhaled corticosteroid and long-acting β2-agonist: budesonide/formoterol and fluticasone/salmeterol are medicinal products that have been on the market for many years in many countries and they are often prescribed both in asthma and COPD.

Study Design

Study Type:

Interventional

Actual Enrollment :

201 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Effectiveness of Single Inhaler Maintenance and Reliever Therapy With Spiromax® Budesonide/Formoterol (SMART) Versus Fixed Dose Treatment With Diskus® Fluticasone/Salmeterol in Patients With a Chronic Obstructive Pulmonary Disease (COPD)

Actual Study Start Date :

May 1, 2015

Actual Primary Completion Date :

Jun 15, 2019

Anticipated Study Completion Date :

Dec 15, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Spiromax Budesonide/formoterol 1. In Group A, Patients will be treated with Spiromax® budesonide/formoterol 160/4.5 μg two inhalations twice daily + Spiromax® budesonide/formoterol 160/4.5 μg as needed with a maximum of 8 additional inhalations daily.	Drug: Spiromax Budesonide/formoterol 1. In Group A, Patients will be treated with Spiromax® budesonide/formoterol 160/4.5 μg two inhalations twice daily + Spiromax® budesonide/formoterol 160/4.5 μg as needed with a maximum of 8 additional inhalations daily. Other Names: Spiromax® budesonide/formoterol
Active Comparator: Diskus Fluticasone/salmeterol 2. In group B, Patients will be treated with Diskus® fluticasone/salmeterol 500/50 μg one inhalation twice daily + salbutamol 100 μg as needed with a maximum of 8 inhalations daily.	Drug: Diskus Fluticasone/salmeterol 2. In group B, Patients will be treated with Diskus® fluticasone/salmeterol 500/50 μg one inhalation twice daily + salbutamol 100 μg as needed with a maximum of 8 inhalations daily. Other Names: Diskus® Fluticasone/salmeterol

Arm

Intervention/Treatment

Experimental: Spiromax Budesonide/formoterol

1. In Group A, Patients will be treated with Spiromax® budesonide/formoterol 160/4.5 μg two inhalations twice daily + Spiromax® budesonide/formoterol 160/4.5 μg as needed with a maximum of 8 additional inhalations daily.

Drug: Spiromax Budesonide/formoterol

Other Names:

Spiromax® budesonide/formoterol

Active Comparator: Diskus Fluticasone/salmeterol

2. In group B, Patients will be treated with Diskus® fluticasone/salmeterol 500/50 μg one inhalation twice daily + salbutamol 100 μg as needed with a maximum of 8 inhalations daily.

Drug: Diskus Fluticasone/salmeterol

2. In group B, Patients will be treated with Diskus® fluticasone/salmeterol 500/50 μg one inhalation twice daily + salbutamol 100 μg as needed with a maximum of 8 inhalations daily.

Other Names:

Diskus® Fluticasone/salmeterol

Outcome Measures

Primary Outcome Measures

Number of participants with increase in symptoms of dyspnea, cough, sputum production [1 year]

Secondary Outcome Measures

Lung function FEV1 [1 year]

Other Outcome Measures

Cell differential counts in blood [1 year]
Inflammation
Symptoms Questionnaire (CCQ) [1 year]
Gene expression [1 year]
nasal gene expression signature

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age between 40 and 80 years
Smoking history of > 10 pack years
COPD patients with an FEV1 < 80% predicted either or not using inhaled corticosteroids.
At least one COPD exacerbation for which oral prednisolone had to be prescribed during 2 years prior to inclusion in the study

Exclusion Criteria:

History of asthma.
Exacerbation or respiratory tract infection during the last 4 weeks prior to randomization.
Females of childbearing potential without an efficient contraception unless they meet the following definition of post-menopausal: 12 months of natural (spontaneous) amenorrhea or 6 months of spontaneous amenorrhea with serum FSH >40 mIU/mL or the use of one or more of the following acceptable methods of contraception:

Surgical sterilization (e.g. bilateral tubal ligation, hysterectomy).
Hormonal contraception (implantable, patch, oral, injectable).
Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/cream/suppository.
Continuous abstinence.

Periodic abstinence (e.g. calendar, ovulation, symptom-thermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. Reliable contraception should be maintained throughout the study and for 30 days after study drug discontinuation.