Reduction of corticosteroid use in outpatient treatment of exacerbated COPD - Study protocol for a randomized, double-blind, non-inferiority study, (The RECUT-trial)

Abstract

Background: Chronic obstructive pulmonary disease (COPD) is a major public health issue affecting approximately 4% to 7% of the Swiss population. According to current inpatient guidelines, systemic corticosteroids are important in the treatment of acute COPD exacerbations and should be given for 5 to 7 days. Several studies suggest that corticosteroids accelerate the recovery of FEV1 (forced expiratory volume in 1 second), enhance oxygenation, decrease the duration of hospitalization, and improve clinical outcomes. However, the additional therapeutic benefit regarding FEV1 recovery appears to be most apparent in the first 3 to 5 days. No data are available on the optimum duration of corticosteroid treatment in primary-care patients with acute COPD exacerbations. Given that many COPD patients are treated as outpatients, there is an urgent need to improve the evidence base on COPD management in this setting. The aim of this study is to investigate whether a 3-day treatment with orally administered corticosteroids is non-inferior to a 5-day treatment in acute exacerbations of COPD in a primary-care setting.

Methods/design: This study is a prospective double-blind randomized controlled trial conducted in a primary-care setting. It is anticipated that 470 patients with acutely exacerbated COPD will be recruited. Participants are randomized to receive systemic corticosteroid treatment of 40 mg prednisone daily for 5 days (conventional arm, n = 235) or for 3 days followed by 2 days of placebo (experimental arm, n = 235). Antibiotic treatment for 7 days is given to all patients with CRP ≥ 50 mg/l, those with a known diagnosis of bronchiectasis, or those presenting with Anthonisen type I exacerbation. Additional treatment after inclusion is left at the discretion of the treating general practitioner. Follow-up visits are performed on days 3 and 7, followed by telephone interviews on days 30, 90, and 180 after inclusion in the study. The primary endpoint is the time to next exacerbation during the 6-month follow-up period.

Discussion: The study is designed to assess whether a 3-day course of corticosteroid treatment is not inferior to the conventional 5-day treatment course in outpatients with exacerbated COPD regarding time to next exacerbation. Depending on the results, this trial may lead to a reduction in the cumulative corticosteroid dose in COPD patients.

Trial registration: ClinicalTrials.gov, NCT02386735. Registered on 12 March 2015.

Keywords: AECOPD; COPD; Corticosteroids; Exacerbation; Primary care.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1

Summary of RECUT trial assessments performed at different time points. 1) Sex, age, weight, height, nationality, detailed medical history, CRP, plasma glucose, leucocyte cell count, respiratory rate, heart rate, blood pressure, pulse oximetry, body temperature, spirometry, mMRC, CAT, and quality and quantity of sputum and coughing. 2) All variables in 1) except demographic variables, but in addition treatment failure, hospitalization, mortality, change in medication, cumulative GC dose, clinically manifested side effects of GC or other medication. CAT only on day 7. 3) mMRC, CAT, quality and quantity of sputum and coughing, re-exacerbation, hospitalization, mortality, change in medication, cumulative GC dose, and clinically manifested side effects of GC or other medication. 4) Intervention (COPD self-management, smoking cessation), comments, and if lost to follow-up. CAT COPD assessment test, COPD chronic obstructive pulmonary disease, CRP C-reactive protein, GC glucocorticoid, mMRC Modified British Medical Research Council Dyspnea Scale