1. Sarah Struthers, MD March 19, 2015
Effect of Corticosteroids on Treatment Failure Among Hospitalized Patients with Severe Community-Acquired Pneumonia and High Inflammatory Response Torres, et al. JAMA. 2015;313(7):
LSU Journal Club
Sarah Struthers, MD
March 19, 2015

2. Background
In patients with CAP, an excessive host inflammatory response has been associated with treatment failure and mortality
Prior studies of corticosteroid use in CAP to blunt this inflammatory response have yielded mixed results. However, these studies have not looked exclusively at the most seriously ill patients
Two recent meta-analyses found improved mortality in the subgroup of patients with severe CAP that received corticosteroids

3. Hypothesis
Corticosteroids may reduce treatment failure in hospitalized patients with severe CAP and high inflammatory response.

4. Study Design & Methodology
Multicenter, randomized, double-blind, placebo-controlled trial at 3 Spanish teaching hospitals
Enrollment period: June February 2012

5. Patient Selection & Enrollment
Inclusion Criteria:
Age >18
Clinical symptoms suggesting CAP (cough, fever, pleuritic CP, dyspnea)
New infiltrate on CXR
Met severe CAP criteria (defined by modified ATS Criteria or Class V PSI)
CRP level >150 mg/L at admission

6. Patient Selection & Enrollment Cont.
Excluson Criteria:
Prior treatment with systemic corticosteroids
Nosocomial pneumonia
Immunosuppression
Pre-existing condition with life expectancy <3 months
Uncontrolled DM
Major GI bleed in last 3 months
Other condition requiring treatment with greater than 1 mg/kg/day of methylprednisolone (MPDN) or equivalent
H1N1 or influenza A

7. Intervention
IV bolus MDPN 0.5 mg/kg every 12 hours OR placebo started within 36 hours of hospital admission and continued for 5 days

8. Primary Endpoint Rate of treatment failure:
Early treatment failure: Clinical deterioration within 72 hours of admission
Development of shock, need for mechanical ventilation not present on admit, death
Late treatment failure: Clinical deterioration from hours
Radiographic progression (increase in pulmonary infiltrates >50% from baseline), PaO2/FIO2 <200 or RR >30 in non-intubated patients + above

9. Secondary Endpoints - Time to clinical stability
- Temp <37.2, HR <100, SBP >90, PaO2 >60 or on baseline home O2, switch to po antibiotics
- Length of hospital and ICU stays
- In-hospital mortality

13. Statistical Analysis
Categorical variables were compared using the Fisher-Exact test and patients were analyzed according intention-to-treat and per-protocol analyses
Logistic regression analyses were performed that adjusted for differences in baseline characteristics and potential confounders (septic shock, procalcitonin and IL-10 at day 1, year of admission and center)

16. Results
There was significantly less treatment failure in the MPDN group, both in the ITT and per-protocol population
- Primarily due to fewer cases of late treatment failure with radiographic progression as a primary component
- Logistic regression analyses revealed less treatment failure in MPDN group both with and without adjustment for differences in baseline characteristics and potential confounders

17. Results Cont…
No significant differences observed among secondary clinical outcomes
Adverse events were evenly distributed across the 2 groups
Post-hoc subanalyses of treatment failure removing radiographic progression variable found that the beneficial effects of corticosteroids remained for the ITT group but not for per-protocol population

18. Conclusions
Concomitant therapy with methylprednisolone reduces treatment failure in patients with both severe CAP and a high inflammatory response

19. Study Limitations
Treatment failure in placebo group lower than predicted yielding an underpowered study
Long duration of study
Results not generalizable to all patients with CAP
No assessment of baseline adrenal function
Despite being stated in hypothesis, changes in inflammatory markers were not treated as outcome measure
Decrease in radiographic progression—Do we care?

20. Thank you