Efficacy and safety of early target-controlled plasma volume replacement with a balanced gelatine solution versus a balanced electrolyte solution in patients with severe sepsis/septic shock: study protocol, design, and rationale of a prospective, randomized, controlled, double-blind, multicentric, international clinical trial : GENIUS-Gelatine use in ICU and sepsis.

BACKGROUND: Sepsis is associated with capillary leakage and vasodilatation and leads to hypotension and tissue hypoperfusion. Early plasma volume replacement is required to achieve haemodynamic stability (HDS) and maintain adequate tissue oxygenation. The right choice of fluids to be used for plasma volume replacement (colloid or crystalloid solutions) is still a matter of debate, and large trials investigating the use of colloid solutions containing gelatine are missing. This study aims to investigate the efficacy and safety of plasma volume replacement using either a combined gelatine-crystalloid regime (1:1 ratio) or a pure crystalloid regime. METHODS: This is a prospective, controlled, randomized, double-blind, international, multicentric phase IV study with two parallel groups that is planned to be conducted at European intensive care units (ICUs) in a population of patients with hypovolaemia in severe sepsis/septic shock. A total of 608 eligible patients will be randomly assigned to receive either a gelatine-crystalloid regime (Gelaspan® 4% and Sterofundin® ISO, B. Braun Melsungen AG, in a 1:1 ratio) or a pure crystalloid regime (Sterofundin® ISO) for plasma volume replacement. The primary outcome is defined as the time needed to achieve HDS. Plasma volume replacement will be target-controlled, i.e. fluids will only be administered to volume-responsive patients. Volume responsiveness will be assessed through passive leg raising or fluid challenges. The safety and efficacy of both regimens will be assessed daily for 28 days or until ICU discharge (whichever occurs first) as the secondary outcomes of this study. Follow-up visits/calls will be scheduled on day 28 and day 90. DISCUSSION: This study aims to generate evidence regarding which regimen-a gelatine-crystalloid regimen or a pure crystalloid regimen-is more effective in achieving HDS in critically ill patients with hypovolaemia. Study participants in both groups will benefit from the increased safety of target-controlled plasma volume replacement, which prevents fluid administration to already haemodynamically stable patients and reduces the risk of harmful fluid overload. TRIAL REGISTRATION: The European clinical trial database EudraCT 2015-000057-20 and the ClinicalTrials.gov Protocol Registration and Results System ClinicalTrials.gov NCT02715466 . Registered on 17 March 2016.

Proceedings From FDA/A.S.P.E.N. Public Workshop: Clinical Trial Design for Intravenous Fat Emulsion Products, October 29, 2013.

The development of intravenous fat emulsion (IVFE) is the culmination of physiological, biochemical, nutritional, and medical scientific advancements. IVFEs have the ability to deliver critical nutritional substrates to the patient. Recent literature purports that they may also play roles in modulation of immune functionality and pulmonary physiology, but data supporting these potential benefits are limited. While soybean-based IVFEs have comprised the dominant fat in U.S. markets, a number of other novel IVFEs may prove to optimize the care of children and adults in both hospitalized and home settings. The October 2013 U.S. Food and Drug Administration (FDA)/American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) Public Workshop brought together scientists, researchers, and clinical experts to present updated clinical perspectives of IVFEs, including historical development, current state of usage throughout the world, and considerations for the regulatory approval of new IVFEs in the United States.