Effectiveness of Continuous Endotracheal Cuff Pressure Control for the Prevention of Ventilator-Associated Respiratory Infections: An Open-Label Randomized, Controlled Trial.

BACKGROUND: An endotracheal tube cuff pressure between 20 and 30 cmH2O is recommended to prevent ventilator-associated respiratory infection (VARI). We aimed to evaluate whether continuous cuff pressure control (CPC) was associated with reduced VARI incidence compared with intermittent CPC. METHODS: We conducted a multicenter open-label randomized controlled trial in intensive care unit (ICU) patients within 24 hours of intubation in Vietnam. Patients were randomly assigned 1:1 to receive either continuous CPC using an automated electronic device or intermittent CPC using a manually hand-held manometer. The primary endpoint was the occurrence of VARI, evaluated by an independent reviewer blinded to the CPC allocation. RESULTS: We randomized 600 patients; 597 received the intervention or control and were included in the intention to treat analysis. Compared with intermittent CPC, continuous CPC did not reduce the proportion of patients with at least one episode of VARI (74/296 [25%] vs 69/301 [23%]; odds ratio [OR] 1.13; 95% confidence interval [CI] .77-1.67]. There were no significant differences between continuous and intermittent CPC concerning the proportion of microbiologically confirmed VARI (OR 1.40; 95% CI .94-2.10), the proportion of intubated days without antimicrobials (relative proportion [RP] 0.99; 95% CI .87-1.12), rate of ICU discharge (cause-specific hazard ratio [HR] 0.95; 95% CI .78-1.16), cost of ICU stay (difference in transformed mean [DTM] 0.02; 95% CI -.05 to .08], cost of ICU antimicrobials (DTM 0.02; 95% CI -.25 to .28), cost of hospital stay (DTM 0.02; 95% CI -.04 to .08), and ICU mortality risk (OR 0.96; 95% CI .67-1.38). CONCLUSIONS: Maintaining CPC through an automated electronic device did not reduce VARI incidence. CLINICAL TRIAL REGISTRATION: NCT02966392.

A statistical analysis plan for the Adjunctive Corticosteroids for Tuberculous meningitis in HIV-positive adults (ACT HIV) clinical trial.

TBM is the most severe form of tuberculosis. Clinical trial data are required to provide an evidence base for adjunctive dexamethasone in HIV-positive individuals with TBM, and to guide clinical practice. This document details the planned analyses at 12 months post randomisation for the ACT HIV clinical trial (NCT03092817); 'a randomised double-blind placebo-controlled trial of adjunctive dexamethasone for the treatment of HIV co-infected adults with tuberculous meningitis (TBM)'. The primary endpoint of the ACT HIV trial is death (from any cause) over the first 12 months after randomisation. This statistical analysis plan expands upon and updates the analysis plan outlined in the published study protocol.