Trial Registration  |  Protocol 

The ABC post-ICU trial is a multicentre, randomised controlled study examining whether active treatment of anaemia after intensive care unit discharge improves recovery in ICU survivors. Anaemia is highly prevalent at ICU discharge and may contribute to fatigue, physical disability, and poor health-related quality of life following critical illness. Adult patients with haemoglobin ≤94 g/L who are deemed ready for ICU discharge are randomised to either usual care or an active transfusion strategy. Usual care follows a restrictive transfusion threshold, with red blood cell transfusion triggered below 70 g/L and a target haemoglobin of 70–90 g/L. The intervention group receives single-unit red blood cell transfusions to achieve a haemoglobin target of 100–120 g/L during the remainder of the acute hospital stay. The primary outcome is physical health-related quality of life at 90 days. Secondary outcomes include fatigue, activities of daily living, mental health-related quality of life, mortality, and hospital length of stay. By focusing on patient-centred recovery rather than short-term mortality, ABC post-ICU addresses a critical evidence gap in post-intensive care care pathways.

Trial Registration  |  Protocol  |  Pilot Trial

The SODa-BIC trial is an international, multicentre, randomised, double-blind study evaluating sodium bicarbonate therapy for metabolic acidosis in critically ill patients receiving vasopressor support. The trial plans to enrol 500 adult ICU patients with confirmed metabolic acidosis and shock, randomising them to intravenous sodium bicarbonate or placebo (5% dextrose). The intervention uses 8.4% sodium bicarbonate (1000 mEq/L), diluted and infused initially at 100 mL/h, with protocolised titration to achieve a target pH ≥7.30 and base excess ≥0 over a maximum of five hours. The primary outcome is major adverse kidney events within 30 days (MAKE30), a composite of death, need for renal replacement therapy, or persistent renal dysfunction. Secondary outcomes include 30- and 90-day mortality, use of renal replacement therapy, and ICU- and vasopressor-free days. By focusing on a haemodynamically unstable population, SODa-BIC aims to provide definitive evidence to guide the use of bicarbonate therapy in a common and controversial ICU setting.

Trial Registration  |  Protocol

SAVE-ICU is a multicentre, pragmatic, open-label randomised controlled trial evaluating whether inhaled volatile anaesthetic sedation (isoflurane or sevoflurane) improves outcomes compared with standard intravenous sedation in mechanically ventilated adults with acute hypoxaemic respiratory failure, including both COVID-19 and non-COVID-19 causes. Conducted across ICUs in Canada and the USA, the trial enrols adults with a PaO₂/FiO₂ ratio ≤300 mm Hg who are expected to require ongoing sedation and ventilation. Patients are randomised 1:1 to inhaled or intravenous sedation delivered using usual-care ICU protocols. The study employs a hierarchical outcome design developed during the COVID-19 pandemic to allow flexible, efficient evidence generation under resource constraints. The primary outcome is hospital mortality, with secondary outcomes including ventilator-free days, ICU-free days, and health-related quality of life at 3 months.

Trial Registration  |  Protocol

The MARCH trial is a large UK multicentre, pragmatic phase 3 randomised study investigating whether the addition of the mucoactives carbocisteine, hypertonic saline, or both to usual airway clearance management improves outcomes in critically ill adults with acute respiratory failure . Using a robust 2×2 factorial design, the trial is recruiting nearly 2,000 invasively ventilated patients across more than 40 ICUs. All participants receive standard airway clearance care, with randomisation determining exposure to one or both mucoactive agents. The primary outcome is duration of mechanical ventilation, a key patient-centred and service-critical endpoint. Secondary outcomes include safety, ICU and hospital length of stay, health-related quality of life, and economic impact. By rigorously evaluating therapies that are widely used but poorly evidenced, MARCH seeks to define the true clinical value of mucoactives in everyday critical care practice.

Trial Registration  |  Website

The VICTORY trial is a multicentre, double-blind, randomised controlled study evaluating high-dose intravenous vitamin C in patients with severe, life-threatening burn injury. Adults aged 18 years or older with deep second- and/or third-degree burns involving at least 20% total body surface area and requiring skin grafting are enrolled across more than 40 burn centres worldwide. Participants are randomly allocated to receive intravenous vitamin C at a dose of 200 mg/kg/day for 96 hours or matched placebo, in addition to standard burn care. The trial is grounded in the hypothesis that profound inflammation, oxidative stress, and metabolic derangement following severe burns may be mitigated by high-dose vitamin C, leading to less organ dysfunction and improved recovery. The primary outcome is time to discharge alive from hospital, with secondary outcomes including hospital and ICU length of stay, need for organ support, hospital and 6-month mortality, health-related quality of life, and healthcare resource use. If successful, this inexpensive and widely available intervention could have global impact on outcomes after severe burn injury.

Trial Registration  |  Trial Protocol 

The Fluids in Septic Shock (FISSH) trial examines whether chloride load influences outcomes in patients with early septic shock requiring substantial intravenous fluid resuscitation. This international, multicentre, randomised controlled trial compares strategies based on high-chloride fluids (0.9% saline or high-chloride albumin) versus low-chloride fluids (Ringer’s lactate or low-chloride albumin). By allowing albumin with differing chloride concentrations alongside crystalloid assignment, the trial isolates cumulative chloride exposure rather than fluid class alone. FISSH builds directly on an earlier pilot phase study and targets a high-risk septic shock population most likely to demonstrate clinically meaningful effects. The primary outcome is 30-day mortality, with key secondary outcomes including acute kidney injury and ICU length of stay. With over 1,000 patients enrolled across multiple international centres, FISSH has the potential to guide fluid resuscitation practice for critically ill patients with infection worldwide.