Very restrictive versus standard RBC transfusion strategy in anemic critically ill patients (VeRTEx): protocol for a pilot randomized controlled trial

BACKGROUND: Red blood cell (RBC) transfusions can be a life-saving intervention, particularly in critically ill patients. However, over the past two decades, their potential for harm has become increasingly evident, leading to the adoption of restrictive transfusion strategies. Current guidelines recommend a transfusion threshold of 7.0 g/dL hemoglobin (Hb) in critically ill patients. However evidence for this exact limit is lacking and there is increasing evidence that Hb-levels under 7 g/dL do not inherently lead to increased mortality or morbidity. This study aims to explore the feasibility of a more restrictive RBC transfusion threshold of 5.0 g/dL compared to the current threshold of 7.0 g/dL in the majority of critically ill patients. METHODS: The study will be a prospective randomized controlled pilot trial conducted in critically ill patients (18 years or older). Participants will be randomized to be treated according to a 5.0 g/dL or a 7.0 g/dL RBC transfusion threshold. Transfusions will be administered 1 RBC unit at a time when the assigned threshold is reached. The primary endpoint is the feasibility of the intervention, expressed as protocol compliance, defined as the percentage of RBC transfusions initiated below the assigned threshold. Secondary outcomes include the SOFA score, protocol violations, incidence of major bleeding, early signs of organ hypoperfusion or organ ischemia, use of life support, acute kidney injury, 30-day mortality, ICU and hospital stay duration, readmission rates, and cost-effectiveness. DISCUSSION: This pilot study aims to determine whether employing a more restrictive transfusion threshold of 5.0 g/dL is feasible when compared to the current 7.0 g/dL threshold in critically ill patients. This study could pave the way for a future large-scale trial that may lead to more stringent transfusion policies, potentially improving patient outcomes, reducing transfusion-related risks in critically ill populations and limit the dependence on donor red blood cells. TRIAL REGISTRATION: This trial was registered at highly restrictive vs normal red blood cell transfusion strategy in anemic critically ill patients - A feasibility trial | Research with human participants (identifier: NL-OMON57318) at 12th of February 2025.