Protocol of the Comparison of Two Different Bicarbonate Replacement Fluids during Continuous Veno-Venous Hemofiltration with Regional Citrate Anticoagulation: A Prospective, Randomized, Controlled Trial

Introduction: 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 <inline-formula><mml:math id="m1" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:msubsup><mml:mtext>HCO</mml:mtext><mml:mn>3</mml:mn><mml:mo>−</mml:mo></mml:msubsup></mml:mrow></mml:math></inline-formula> concentration during continuous renal replacement therapy. This prospective trail aimed to compare acid-base balance between a high (HBF) and low (LBF) bicarbonate replacement fluid over a period of 96 h after CVVH initiation using RCA. Methods: This is a prospective, randomized, controlled, open-label, crossover, phase II, single-center 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 h of CVVH. The primary endpoints are the occurrence of at least one pH (>7.45) or <inline-formula><mml:math id="m2" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:msubsup><mml:mtext>HCO</mml:mtext><mml:mn>3</mml:mn><mml:mo>−</mml:mo></mml:msubsup></mml:mrow></mml:math></inline-formula> (>26 mmol/L) excursion within 16–48 h of each treatment phase using a generalized estimating equation approach. The objective was to examine differences of pH and <inline-formula><mml:math id="m3" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:msubsup><mml:mtext>HCO</mml:mtext><mml:mn>3</mml:mn><mml:mo>−</mml:mo></mml:msubsup></mml:mrow></mml:math></inline-formula> between patients who receive LBF and HBF as replacement fluid during CVVH. We hypothesize that during CVVH with LBF, pH, and HCO₃− excursion rates are significantly lower compared to HBF. 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. The trial is registered at <ext-link ext-link-type="uri" xlink:href="http://ClinicalTrials.gov" xmlns:xlink="http://www.w3.org/1999/xlink">ClinicalTrials.gov</ext-link> (NCT04071171) and EudraCT (2019-001262-15). Conclusion: 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.