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

NCT ID: NCT02477397

Last Updated: 2019-07-10

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 201 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-05-01
• Study Completion Date: 2019-12-15

Brief Summary

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

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.

Conditions

COPD

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Spiromax Budesonide/formoterol

Intervention Type: DRUG

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.

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.

Group Type: ACTIVE_COMPARATOR

Diskus Fluticasone/salmeterol

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Spiromax® budesonide/formoterol; Diskus® Fluticasone/salmeterol

Eligibility Criteria

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:

1. Surgical sterilization (e.g. bilateral tubal ligation, hysterectomy).

2. Hormonal contraception (implantable, patch, oral, injectable).

3. Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/cream/suppository.

4. 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.

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Medical Center Groningen

OTHER

Sponsor Role: lead

Responsible Party

Maarten van den Berge

Dr.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Maarten van den Berge, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University Medical Center Groningen

Locations

University Medical Center Groningen

Groningen, , Netherlands

Countries

Netherlands

References

Wisselink HJ, Pelgrim GJ, Rook M, Dudurych I, van den Berge M, de Bock GH, Vliegenthart R. Improved precision of noise estimation in CT with a volume-based approach. Eur Radiol Exp. 2021 Sep 10;5(1):39. doi: 10.1186/s41747-021-00237-x.

Reference Type: DERIVED

PMID: 34505172 (View on PubMed)

Other Identifiers

SMART2014

Identifier Type: -

Identifier Source: org_study_id