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

Medical University Innsbruck

Status and phase: Completed; Phase 2

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

Treatments: Drug: CVVH with Biphozyl® in the first 48h after randomization; Drug: CVVH with Phoxilium® 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®)

Study type: Interventional

Funder types: Other

Identifiers

NCT04071171

EudraCT No. 2019-001262-15

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 88 patients

Sex: All

Ages: 18 to 120 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Age ≥ 18 years
2. Admission to Intensive Care Unit
3. Indication for CVVH as determined by the attending physician
4. Planned CVVH treatment time ≥ 48 hours
5. Written informed consent or deferred consent or legally acceptable representative consent

Exclusion criteria

1. Lack of commitment to provide CVVH as part of limitation of ongoing life support
2. Presence of a drug overdose that may result in acid-base-disorders and/or a shift of electrolytes
3. Receipt of CVVH within the previous 72 hours
4. Dialysis dependent end-stage renal disease
5. Pregnancy, must be ruled out by anamnesis and/or blood or urine pregnancy test
6. Combination of severely impaired liver function and shock with muscle hypoperfusion
7. Co-enrollment in another trial, which could have a plausible interaction with the acid-base-status and/or any electrolytes
8. Subjects, who are legally exempted from participation in clinical trials (e.g. persons held in an institution by legal or official order)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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88 participants in 2 patient groups

Phoxilium®

Active Comparator group

Treatment:

Drug: CVVH with Phoxilium® in the first 48h after randomization

Drug: CVVH with Phoxilium® in the second 48h after randomization (after previous 48h with Biphozyl®)

Biphozyl®

Experimental group

Treatment:

Drug: CVVH with Biphozyl® in the first 48h after randomization

Drug: CVVH with Biphozyl® in the second 48h after randomization (after previous 48h with Phoxilium®)