Dexamethasone for parapneumonic pleural effusion in children: A randomized, double-blind, phase II, clinical trial

Background. Pleural infections lead to long hospitalizations. In this trial, we investigate whether dexamethasone decreases the time to recovery from pleural infection. Also we evaluate complications and adverse events associated with dexamethasone. Methods. CORTEEC is a multi-center, phase II, double-blind, parallel-group, placebo- controlled clinical trial. We recruited children with parapneumonic pleural effusion at 9 Spanish hospitals. Participants were randomly placed into placebo or dexamethasone in a 1:1 ratio. Patients were scheduled for 0.25 mg/kg/qid of intravenous dexamethasone or placebo. The primary endpoint was the time to recovery (in hours). We performed an intention-to-treat analysis with all patients with at least 1 administration of study drug. Results. A total of 60 patients were assigned to dexamethasone (n = 30) and placebo (n = 30) between 1 January 2010, and 31 May 2015. A total of 57 (95%) patients completed the protocol. Dexamethasone was better than placebo with respect to time to recovery. The hazard ratio (HR) for recovery was 1.85 (95% confidence interval [CI], 1.08 to 3.17; P = 0.024). In the multivariate Cox model, the superiority of dexamethasone was consistent, regardless of severity group (HR, 1.73; 95% CI, 1.02 to 2.9; P = 0.042). The median time to recovery for patients on dexamethasone was 68 hours (2.8 days, 38%) shorter than patients on placebo. The median time to recovery for patients with simple effusion on dexamethasone was 76 hours (3.1 days, 61%) shorter than patients with simple effusion on placebo. The median time to recovery for patients with complicated effusion on dexamethasone was 14 hours (0.5 days, 6%) shorter than patients with complicated effusion on placebo. The difference in the effect of dexamethasone in the two severity groups was not statistically significant (P = 0.138 for interaction). There were no significant differences in complications or adverse events attributable to the study drugs, except for hyperglycemia. Fifteen (50%) patients on DXM and 6 (20%) patients on placebo had hyperglycemia (P = 0.01). Risk ratio of dexamethasone for hyperglycemia was 4; 95% CI, 1.2 to 12.5. Conclusion. In this trial, dexamethasone was a safe and effective adjunctive therapy for parapneumonic pleural effusion.