Trial Registration  |  Trial Protocol

Intravenous drug diluents contribute a substantial sodium load in critically ill patients, but whether changing the default diluent reduces ICU-acquired hypernatraemia remains uncertain. SWEET-WATER is a multicentre, pragmatic, open-label, stepped-wedge cluster randomised trial embedded in routine care, with a projected sample of 4,485 adults across 12 intensive and intermediate care units in Germany. Patients admitted for acute brain injury or with sodium <130 mmol/L are excluded. Units switch in a randomised sequence from sodium chloride 0.9% to glucose 5% as the default diluent for compatible intravenous medications, with one unit switching every four weeks. Patients admitted during each unit’s four-week transition period are excluded from analysis.

The primary outcome is ICU-acquired hypernatraemia >150 mmol/L through day 28, with patients whose admission sodium is ≥150 mmol/L excluded from this analysis. The key secondary outcome is days alive and free of the ICU through day 28, tested hierarchically if the primary analysis is statistically significant. Exploratory outcomes include mortality, ventilator-free and hospital-free days, dialysis-dependent acute kidney injury, and safety outcomes including hyponatraemia and hyperglycaemia. The projected sample provides approximately 99% power to detect a reduction in hypernatraemia from 17.9% to 10.5%, using a significance level of 0.05.

Trial Registration  |  Trial Protocol

Fluid overload may prolong invasive ventilation, but the optimal timing and intensity of fluid removal remain uncertain. CONFIDENCE is an open-label, multicentre randomised superiority trial designed to enrol 1,000 adults across 10 Dutch ICUs. Patients are randomised within 24 hours of starting invasive ventilation and must be expected to require ventilation for more than another 24 hours. Following haemodynamic stabilisation, the intervention uses daily 12-region lung ultrasound to guide deresuscitation until ICU discharge or day 28. Recommended daily fluid balances are at least 1,500 mL negative for substantial pulmonary oedema, at least 500 mL negative for lesser oedema or significant pleural effusion, and neutral in their absence, compared with clinician-directed deresuscitation without lung ultrasound guidance. The primary outcome is the number of days alive and free from ventilation through day 28. Secondary outcomes include 28- and 90-day mortality, ICU and hospital length of stay, cumulative fluid balance and acute kidney injury. The planned sample provides 80% power to detect a two-day increase in ventilator-free days, from 13 to 15, using a two-sided significance level of 0.05.

Trial Registration  |  Trial Protocol

The VATICAN trial is a multicentre, open-label, randomised noninferiority trial addressing whether ventilator-associated tracheobronchitis (VAT), for which the optimal antibiotic strategy remains uncertain, can safely be managed without routine antibiotics. It will enrol 590 adults in up to 50 Brazilian ICUs who have received invasive mechanical ventilation for ≥48 hours and have suspected VAT without VAP, haemodynamic instability due to infection, or another indication for antibiotics. Patients are randomised to watchful waiting, with no antibiotics for VAT unless VAP, haemodynamic instability/sepsis, unexplained new organ dysfunction or another infection develops, or routine antimicrobial treatment for 7 days (5 days permitted with complete clinical improvement). The primary outcome is ventilator-free days at day 28, with VAP-free survival at day 28 as the key secondary outcome. Other outcomes include 28-day mortality, VAP, ICU- and antibiotic-free days, SOFA score, multidrug-resistant organisms, hospital-acquired infection and serious adverse events. The trial seeks to demonstrate noninferiority of watchful waiting using a 20% noninferiority margin, corresponding to 1.5 fewer ventilator-free days at day 28.