Effectiveness of a Bundled Intervention Including Adjunctive Corticosteroids on Outcomes of Hospitalized Patients With Community-Acquired Pneumonia: A Stepped-Wedge Randomized Clinical Trial

Key PointsQuestionDoes a bundle of evidence-supported treatments (including adjunctive corticosteroids) improve the outcomes of patients with community-acquired pneumonia under conditions of routine care? FindingsIn this stepped-wedge, cluster-randomized effectiveness trial of 816 patients hospitalized with community-acquired pneumonia, a bundled intervention aiming to optimize treatment with corticosteroids, early mobilization, early switch to oral antibiotics, and screening for malnutrition had no significant effect on length of hospital stay, readmissions, mortality, or other complications of community-acquired pneumonia and resulted in a higher incidence of gastrointestinal bleeding when compared with usual care. MeaningThis process-of-care bundle failed to improve outcomes and may have increased risks of adverse events; it cannot be recommended for patients hospitalized with community-acquired pneumonia. ImportanceCommunity-acquired pneumonia remains a leading cause of hospitalization, mortality, and health care costs worldwide. Randomized clinical trials support the use of adjunctive corticosteroids, early progressive mobilization, antibiotic switching rules, and dietary interventions in improving outcomes. However, it is uncertain whether implementing these interventions will translate into effectiveness under routine health care conditions. ObjectiveTo evaluate the effectiveness of a bundle of evidence-supported treatments under conditions of routine care in a representative population hospitalized for community-acquired pneumonia. Design, Setting, and ParticipantsA double-blind, stepped-wedge, cluster-randomized clinical trial with 90-day follow-up was conducted between August 1, 2016, and October 29, 2017, in the general internal medicine service at 2 tertiary hospitals in Melbourne, Australia, among a consecutive sample of patients with community-acquired pneumonia. The primary analysis and preparation of results took place between May 14 and November 25, 2018. InterventionsTreating clinical teams were advised to prescribe prednisolone acetate, 50 mg/d, for 7 days (in the absence of any contraindication) and de-escalate from parenteral to oral antibiotics according to standardized criteria. Algorithm-guided early mobilization and malnutrition screening and treatment were also implemented. Main Outcomes and MeasuresHospital length of stay, mortality, readmission, and intervention-associated adverse events (eg, gastrointestinal bleeding and hyperglycemia). ResultsA total of 917 patients were screened, and 816 (351 women and 465 men; mean [SD] age, 76 [13] years) were included in the intention-to-treat analysis, with 401 patients receiving the intervention and 415 patients in the control group. An unadjusted geometric mean ratio of 0.95 (95% CI, 0.78-1.16) was observed for the difference in length of stay (days) between the intervention and control groups. Similarly, no significant differences were observed for the secondary outcomes of mortality and readmission, and the results remained unchanged after further adjustment for sex and age. The study reported higher proportions of gastrointestinal bleeding in the intervention group (9 [2.2%]) compared with the controls (3 [0.7%]), with an unadjusted estimated difference in mean proportions of 0.008 (95% CI, 0.005-0.010). Conclusions and RelevanceThis bundled intervention including adjunctive corticosteroids demonstrated no evidence of effectiveness and resulted in a higher incidence of gastrointestinal bleeding. Efficacy of individual interventions demonstrated in clinical trials may not necessarily translate into effectiveness when implemented in combination and may even result in net harm. Trial RegistrationClinicalTrials.gov identifier: NCT02835040 This randomized clinical trial evaluates the effectiveness of a bundle of evidence-supported treatments under conditions of routine care in a representative population hospitalized for community-acquired pneumonia.