Protocol of the comparison of two different bicarbonate replacement fluids during CVVH with RCA: a Prospective, Randomized, Controlled Trial.

Background: Acid-base disturbances are common issues during continuous veno-venous hemofiltration (CVVH). Especially using regional citrate anticoagulation (RCA) recent studies have shown that control in intracorporal pH and HCO3- concentration may be improved when the replacement fluid is changed to a solution with a lower HCO3- concentration during continuous renal replacement therapy (CRRT). This prospective trail aims to compare acid base balance between a high (HBF) and low (LBF) bicarbonate replacement fluid over a period of 96 hours after CVVH initiation using RCA. Methods/ design: This is a prospective, randomized, controlled, open-label, cross-over, Phase II, single-centre pilot study involving critically ill patients requiring RRT. The two replacement fluids (Phoxilium and Biphozyl) are compared in two groups with 1:1 block randomization and consecutive crossover after 48 hours of CVVH. The primary endpoints are the occurrence of at least one pH (> 7.45) or HCO3- (> 26 mmol/l) excursion within 16-48 hours of each treatment phase using a Generalized Estimating Equation (GEE) approach.

Primary Objective: The objective is to examine differences of pH and HCO3- between patients who receive LBF and HBF as replacement fluid during CVVH.

Hypothesis: We hypothesize that during CVVH with LBF, pH and HCO3- excursion rates are significantly lower compared to HBF.

Trial Status: Recruitment of 88 study participants is ongoing, with the trial expected to be completed in 2025. Data cleaning, analysis, and publication preparation will follow thereafter.

Discussion: Given the broad inclusion and restricted exclusion criteria, we expect the results of the BiPhox-Trial to be broadly applicable to patients in need of CVVH with RCA in the intensive care setting. This trial aims to determine whether the use of LBF results in more stable acid-base parameters compared to HBF during CVVH with RCA in critically ill patients, and may guide therapeutic decisions in clinical practice.