title: Short-term vs conventional glucocorticoid therapy in acute exacerbations of chronic obstructive pulmonary disease: the REDUCE randomized clinical trial.
abstract: OBJECTIVE
  International guidelines advocate a 7- to 14-day course of systemic glucocorticoid therapy in acute exacerbations of chronic obstructive pulmonary disease (COPD). However, the optimal dose and duration are unknown.
  
  
  OBJECTIVE
  To investigate whether a short-term (5 days) systemic glucocorticoid treatment in patients with COPD exacerbation is noninferior to conventional (14 days) treatment in clinical outcome and whether it decreases the exposure to steroids. DESIGN, SETTING, AND PATIENTS REDUCE: (Reduction in the Use of Corticosteroids in Exacerbated COPD), a randomized, noninferiority multicenter trial in 5 Swiss teaching hospitals, enrolling 314 patients presenting to the emergency department with acute COPD exacerbation, past or present smokers (≥20 pack-years) without a history of asthma, from March 2006 through February 2011.
  
  
  METHODS
  Treatment with 40 mg of prednisone daily for either 5 or 14 days in a placebo-controlled, double-blind fashion. The predefined noninferiority criterion was an absolute increase in exacerbations of at most 15%, translating to a critical hazard ratio of 1.515 for a reference event rate of 50%.
  
  
  METHODS
  Time to next exacerbation within 180 days.
  
  
  RESULTS
  Of 314 randomized patients, 289 (92%) of whom were admitted to the hospital, 311 were included in the intention-to-treat analysis and 296 in the per-protocol analysis. Hazard ratios for the short-term vs conventional treatment group were 0.95 (90% CI, 0.70 to 1.29; P = .006 for noninferiority) in the intention-to-treat analysis and 0.93 (90% CI, 0.68 to 1.26; P = .005 for noninferiority) in the per-protocol analysis, meeting our noninferiority criterion. In the short-term group, 56 patients (35.9%) reached the primary end point; 57 (36.8%) in the conventional group. Estimates of reexacerbation rates within 180 days were 37.2% (95% CI, 29.5% to 44.9%) in the short-term; 38.4% (95% CI, 30.6% to 46.3%) in the conventional, with a difference of -1.2% (95% CI, -12.2% to 9.8%) between the short-term and the conventional. Among patients with a reexacerbation, the median time to event was 43.5 days (interquartile range [IQR], 13 to 118) in the short-term and 29 days (IQR, 16 to 85) in the conventional. There was no difference between groups in time to death, the combined end point of exacerbation, death, or both and recovery of lung function. In the conventional group, mean cumulative prednisone dose was significantly higher (793 mg [95% CI, 710 to 876 mg] vs 379 mg [95% CI, 311 to 446 mg], P < .001), but treatment-associated adverse reactions, including hyperglycemia and hypertension, did not occur more frequently.
  
  
  CONCLUSIONS
  In patients presenting to the emergency department with acute exacerbations of COPD, 5-day treatment with systemic glucocorticoids was noninferior to 14-day treatment with regard to reexacerbation within 6 months of follow-up but significantly reduced glucocorticoid exposure. These findings support the use of a 5-day glucocorticoid treatment in acute exacerbations of COPD.
  
  
  BACKGROUND
  isrctn.org Identifier: ISRCTN19646069.
authors.affiliation: Clinic of Internal Medicine, University Hospital of Basel, Switzerland.
authors.forename: Jörg D
authors.initials: JD
authors.lastname: Leuppi
authors.forename: Philipp
authors.initials: P
authors.lastname: Schuetz
authors.forename: Roland
authors.initials: R
authors.lastname: Bingisser
authors.forename: Michael
authors.initials: M
authors.lastname: Bodmer
authors.forename: Matthias
authors.initials: M
authors.lastname: Briel
authors.forename: Tilman
authors.initials: T
authors.lastname: Drescher
authors.forename: Ursula
authors.initials: U
authors.lastname: Duerring
authors.forename: Christoph
authors.initials: C
authors.lastname: Henzen
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Leibbrandt
authors.forename: Sabrina
authors.initials: S
authors.lastname: Maier
authors.forename: David
authors.initials: D
authors.lastname: Miedinger
authors.forename: Beat
authors.initials: B
authors.lastname: Müller
authors.forename: Andreas
authors.initials: A
authors.lastname: Scherr
authors.forename: Christian
authors.initials: C
authors.lastname: Schindler
authors.forename: Rolf
authors.initials: R
authors.lastname: Stoeckli
authors.forename: Sebastien
authors.initials: S
authors.lastname: Viatte
authors.forename: Christophe
authors.initials: C
authors.lastname: von Garnier
authors.forename: Michael
authors.initials: M
authors.lastname: Tamm
authors.forename: Jonas
authors.initials: J
authors.lastname: Rutishauser
mesh_terms: D000208:Acute Disease; D000368:Aged; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage*; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000503:physiopathology; D012129:Respiratory Function Tests; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D005938:Glucocorticoids; D011241:Prednisone