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

Abstract

BackgroundChronic 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/designThis 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.DiscussionThe 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 registrationClinicalTrials.gov, NCT02386735. Registered on 12 March 2015.

Efficacy and Safety of Different Doses of Systemic Corticosteroids in COPD Exacerbation

“…The RECUT trial, which is currently recruiting subjects, is designed to Study or Subgroup Aaron 2003Chen 2008aChen 2008b Total (95% CI) Total events Heterogeneity: Chi 2 = 0.40, df = 2 (P = .82); I 2 = 0% Test for overall effect: Z = 1.76 (P = .08) explore whether a 3-d treatment with orally administered SCS is noninferior to 5-d treatment in subjects with COPD exacerbation, and whether total corticosteroid exposure can be reduced by shorter therapy duration. 40 In the current investigation, there is a trend to reduce the duration of SCS courses in subjects with COPD exacerbation. In the Bullard 1996Niewoehner 1999 Subtotal (95% Cl) Heterogeneity: Chi 2 = 1.70, df = 1 (P = .19); I 2 = 41% Test for overall effect: Z = 2.88 (P = .004)…”

Long- versus short-duration systemic corticosteroid regimens for acute exacerbations of COPD: A systematic review and meta-analysis of randomized trials and cohort studies

“…Relatedly, our sole study that specifically assessed outpatients raises questions about the generalizability of our results in outpatients, which represent over 80% of all exacerbations [4]. RECUT—a currently ongoing RCT which specifically recruits outpatients—will hopefully shed more light on this issue [38].…”

Long- versus short-duration systemic corticosteroid regimens for acute exacerbations of COPD: A systematic review and meta-analysis of randomized trials and cohort studies

“…However, data between trials using different regimen lengths were generally not heterogenous with one another, suggesting that the clinical effects of corticosteroids between each of those ranges are minimal. The main exception is Sayiner 2001's FEV 1 data, which as stated in the results section may be due to the duration being genuinely lower than the physiologically optimal duration [42]. However, this is only one relatively small and old RCT, so whether this is the case is unclear.…”

“…If this is the case, this heterogeneity may represent a form of dose-dependent relationship between corticosteroid regimen duration and FEV 1 change. Previous research suggests effect of corticosteroids on FEV 1 recovery may be most apparent in the initial 3-5 days of treatment [42]. In that case, the short-duration group of Sayiner 2001 would have ended at the beginning of this period.…”

“…Relatedly, our sole study that specifically assessed outpatients raises questions about the generalizability of our results in outpatients, which represent over 80% of all exacerbations [9]. RECUT-a currently ongoing RCT which specifically recruits outpatients-will hopefully shed more light on this issue [42].…”