Comparison of Biphozyl® and Phoxilium® as a Replacement Fluid During CVVH for AKI in Adults and Their Effects on pH-, Bicarbonate-levels and Respiratory Situation

Study Overview
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Brief Summary
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The primary objectives of the BiPhox-Trial are to demonstrate, that the use of Biphozyl® as a replacement fluid in adult critically ill acute kidney injury (AKI) patients, results in a lower rate of pH excursions and of bicarbonate (HCO3-) excursions compared to the use of Phoxilium® during the studied continuous veno-venous hemofiltration (CVVH) interval with regional citrate anticoagulation (RCA). The secondary objectives of the BiPhox-Trial are to evaluate the time to pH level normalization and the HCO3- substitution rates after initiation of CVVH treatment. Further, to demonstrate that the use of Biphozyl® as a replacement fluid in adult critically ill AKI patients, results in a more stable acid-base-status as well as improved respiratory situation due to lower intracorporeal HCO3- and carbon dioxide levels compared to the use of Phoxilium® during the studied CVVH interval with RCA.

Detailed Description
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After being fully eligible by meeting all inclusion and none of the exclusion criteria, participants will be randomly assigned to one of two groups, either the Phoxilium® - Group or Biphozyl® - Group. After randomization, patients receive either Phoxilium® or Biphozyl® for CVVH initiation and maintenance as a replacement fluid during the first 48 hours (h) of treatment. After the first 48h of CVVH with either Phoxilium® or Biphozyl® a cross-over follows, with another 48h of CVVH with the opposite replacement fluid (Phoxilium® switched to Biphozyl® or Biphozyl® switched to Phoxilium®). In comparison, all patients should receive one session of CVVH with 96h. Resulting from 48h of CVVH with Phoxilium® and 48h of CVVH with Biphozyl® as a replacement fluid. The order is determined by randomization. Anticoagulation is always delivered as pre-filter RCA with Regiocit® (Gambro Lundia AB, Sweden). For antagonisation of Regiocit®, a calcium solution (calcium chloride, with or without magnesium chloride) will be used post-filter.

Official Title
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Comparison of Biphozyl® and Phoxilium® as a Replacement Fluid During CVVH for AKI in Adults and Their Effects on pH-, Bicarbonate-levels and Respiratory Situation - A Prospective, Randomized, Controlled, Open, Cross-over, Phase II, Single-center Pilot Study [BiPhox-Trial]

Conditions
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Replacement Fluid, Critically Ill, Acute Kidney Injury, Renal Replacement Therapy, Continuous Renal Replacement Therapy, Continuous Veno-Venous Hemofiltration, Phoxilium, Biphozyl, Anticoagulation, Regional Citrate Anticoagulation

Intervention / Treatment
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* Drug: CVVH with Phoxilium® in the first 48h after randomization
* Drug: CVVH with Biphozyl® in the first 48h after randomization
* Drug: CVVH with Phoxilium® in the second 48h after randomization (after previous 48h with Biphozyl®)
* Drug: CVVH with Biphozyl® in the second 48h after randomization (after previous 48h with Phoxilium®)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years Admission to Intensive Care Unit Indication for CVVH as determined by the attending physician Planned CVVH treatment time ≥ 48 hours Written informed consent or deferred consent or legally acceptable representative consent Exclusion Criteria: Lack of commitment to provide CVVH as part of limitation of ongoing life support Presence of a drug overdose that may result in acid-base-disorders and/or a shift of electrolytes Receipt of CVVH within the previous 72 hours Dialysis dependent end-stage renal disease Pregnancy, must be ruled out by anamnesis and/or blood or urine pregnancy test Combination of severely impaired liver function and shock with muscle hypoperfusion Co-enrollment in another trial, which could have a plausible interaction with the acid-base-status and/or any electrolytes Subjects, who are legally exempted from participation in clinical trials (e.g. persons held in an institution by legal or official order)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Phoxilium®<br> | Drug: CVVH with Phoxilium® in the first 48h after randomization<br>* After randomization into the Phoxilium®-group, CVVH will be initiated with Phoxilium® as a replacement fluid and maintained for 48h, respectively until the crossover. Anticoagulation is delivered as pre-filter RCA with Regiocit® (Gambro Lundia AB, Sweden). For antagonisation of Regiocit®, a calcium solution (calcium chloride, with or without magnesium chloride) will be used post-filter.<br>Drug: CVVH with Phoxilium® in the second 48h after randomization (after previous 48h with Biphozyl®)<br>* 48h post randomization, respectively after the cross-over CVVH will be continued with Phoxilium® for another 48h. Anticoagulation is delivered as pre-filter RCA with Regiocit® (Gambro Lundia AB, Sweden). For antagonisation of Regiocit®, a calcium solution (calcium chloride, with or without magnesium chloride) will be used post-filter.<br>|
| Experimental: Biphozyl®<br> | Drug: CVVH with Biphozyl® in the first 48h after randomization<br>* After randomization into the Biphozyl®-group, CVVH will be initiated with Biphozyl® as a replacement fluid and maintained for 48h, respectively until the crossover. Anticoagulation is delivered as pre-filter RCA with Regiocit® (Gambro Lundia AB, Sweden). For antagonisation of Regiocit®, a calcium solution (calcium chloride, with or without magnesium chloride) will be used post-filter.<br>Drug: CVVH with Biphozyl® in the second 48h after randomization (after previous 48h with Phoxilium®)<br>* 48h post randomization, respectively after the cross-over CVVH will be continued with Biphozyl® for another 48h. Anticoagulation is delivered as pre-filter RCA with Regiocit® (Gambro Lundia AB, Sweden). For antagonisation of Regiocit®, a calcium solution (calcium chloride, with or without magnesium chloride) will be used post-filter.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pH | Rate of pH excursions from a set range of 7.35-7.45. | 96 hours (48h of CVVH with Phoxilium® vs. 48h of CVVH with Biphozyl®) | 
| HCO3- | Rate of HCO3- excursions from a set range of 22-26 mmol/l. | 96 hours (48h of CVVH with Phoxilium® vs. 48h of CVVH with Biphozyl®) |