STUDY SUMMARY
Shorter and longer regimens produce equal results
Leuppi et al1 used noninferiority methodology to compare a five- and a 14-day course of prednisone 40 mg/d to treat patients with COPD exacerbations. A patient was considered to have an exacerbation if he or she had a change from baseline in two or more of the following: dyspnea, cough, sputum quantity, or purulence.
Participants were patients who presented to the EDs of five Swiss teaching hospitals between March 2006 and February 2011. To be eligible, individuals had to be 40 or older and have at least 20 pack-years of smoking. Exclusion criteria included asthma, mild obstruction (FEV1/FVC > 70%), pneumonia, an estimated survival of less than six months, pregnancy, and lactation.
All the participants (N = 311) received 40 mg methylprednisolone intravenously on day 1, followed by prednisone 40 mg orally on days 2 through 5. The researchers then randomly divided participants into two groups: One group continued to take prednisone 40 mg/d and the other group received a matching placebo for an additional nine days. Participants in both groups also received antibiotics for seven days, twice-daily inhaled steroids, daily tiotropium, and nebulized albuterol, as needed; additional oral glucocorticoids could be administered, as well, at the discretion of the treating physicians.
The primary outcome was the time to the next COPD exacerbation, up to 180 days. Noninferiority between the groups was defined as no more than a 15% absolute increase in exacerbations. The dropout rate was 5.7%, evenly divided between groups. Intention to treat and per-protocol analyses were conducted, and hazard ratios (HRs) were calculated using the Kaplan-Meier method and Cox proportional hazards models.
The time to next COPD exacerbation did not differ between the study groups: 56 days for those on the five-day steroid regimen versus 57 days for those on the
14-day regimen in the intention-to-treat analysis (HR, 0.95). Sensitivity analyses adjusting for baseline characteristics provided similar results, as did the per-protocol analysis.
Secondary outcomes (overall survival; need for mechanical ventilation; need for additional corticosteroids; and clinical performance measures, such as dyspnea score and quality of life) also did not differ between groups. Nor were there differences in hyperglycemia, worsening hypertension, infection, or other adverse effects typically associated with glucocorticoid use. The active treatment group took more than 400 mg more prednisone than the placebo group (mean, 793 mg vs 379 mg, respectively).