TY - JOUR
T1 - Short-term vs conventional glucocorticoid therapy in acute exacerbations of chronic obstructive pulmonary disease: The REDUCE randomized clinical trial
AU - Leuppi, Jörg D.
AU - Schuetz, Philipp
AU - Bingisser, Roland
AU - Bodmer, Michael
AU - Briel, Matthias
AU - Drescher, Tilman
AU - Duerring, Ursula
AU - Henzen, Christoph
AU - Leibbrandt, Yolanda
AU - Maier, Sabrina
AU - Miedinger, David
AU - Müller, Beat
AU - Scherr, Andreas
AU - Schindler, Christian
AU - Stoeckli, Rolf
AU - Viatte, Sebastien
AU - Von Garnier, Christophe
AU - Tamm, Michael
AU - Rutishauser, Jonas
PY - 2013
Y1 - 2013
N2 - Importance: International guidelines advocate a 7- to 14-day course of systemic glucocorticoid therapyin 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. Interventions: 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%. Main Outcome and Measure: 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 and Relevance: 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. Trial Registration: isrctn.org Identifier: ISRCTN19646069 ©2013 American Medical Association. All rights reserved.
AB - Importance: International guidelines advocate a 7- to 14-day course of systemic glucocorticoid therapyin 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. Interventions: 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%. Main Outcome and Measure: 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 and Relevance: 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. Trial Registration: isrctn.org Identifier: ISRCTN19646069 ©2013 American Medical Association. All rights reserved.
U2 - 10.1001/jama.2013.5023
DO - 10.1001/jama.2013.5023
M3 - Article
C2 - 23695200
SN - 1538-3598
VL - 309
SP - 2223
EP - 2231
JO - Journal of the American Medical Association
JF - Journal of the American Medical Association
IS - 21
ER -