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

NCT04071171 | Completed Phase 2

• 1 other identifier: EudraCT No. 2019-001262-15
• Study Type: interventional
• Target: 88
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

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

Outcome Measures

Primary Outcomes (2)

• 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®)

Study Arms (2)

Phoxilium®

ACTIVE COMPARATOR

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

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®)

Interventions

CVVH with Phoxilium® in the first 48h after randomization DRUG

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.

Phoxilium®

CVVH with Biphozyl® in the first 48h after randomization DRUG

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.

Biphozyl®

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

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.

Phoxilium®

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

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.

Biphozyl®

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Medical University Innsbruck: lead

Study Sites (1)

Division of Intensive Care and Emergency Medicine, Department of Internal Medicine, Medical University Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria

Innsbruck, Tyrol, 6020, Austria

Location

Related Publications (2)

• Perschinka F, Koglberger P, Kohler A, Lehner GF, Peer A, Maier S, Ulmer H, Bellmann R, Forni LG, Joannidis M. Comparison of two different bicarbonate replacement fluids during CVVH with RCA: a prospective, randomized, controlled trial. Intensive Care Med. 2025 Dec;51(12):2354-2366. doi: 10.1007/s00134-025-08175-7. Epub 2025 Nov 17.

  PMID: 41247497 DERIVED

• Koglberger P, Perschinka F, Klein SJ, Mayerhofer T, Maier S, Ulmer H, Bellmann R, Joannidis M. Protocol of the Comparison of Two Different Bicarbonate Replacement Fluids during Continuous Veno-Venous Hemofiltration with Regional Citrate Anticoagulation: A Prospective, Randomized, Controlled Trial. Blood Purif. 2025;54(12):723-732. doi: 10.1159/000547401. Epub 2025 Aug 4.

  PMID: 40759107 DERIVED

MeSH Terms

Conditions

Critical Illness; Acute Kidney Injury

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• Michael Joannidis, Univ.-Prof., MD

  Medical University Innsbruck

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 23, 2019
• First Posted: August 28, 2019
• Study Start: August 1, 2020
• Primary Completion: November 15, 2023
• Study Completion: March 11, 2024
• Last Updated: March 13, 2024

Record last verified: 2024-03

Locations

AU (1)