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

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]

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.

Study Overview

• Status: Completed
• Conditions: Acute Kidney Injury; Critically Ill; Renal Replacement Therapy; Continuous Renal Replacement Therapy; Continuous Veno-Venous Hemofiltration; Replacement Fluid; Phoxilium; Biphozyl; Anticoagulation; Regional Citrate Anticoagulation
• Intervention / 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®); 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®)

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 88
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Michael Joannidis, Univ.-Prof., MD; Phone Number: +43 512 504 24180; Email: michael.joannidis@i-med.ac.at

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Phoxilium®	Drug: CVVH with Phoxilium® in the first 48h after randomization; 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.; Drug: CVVH with Phoxilium® in the second 48h after randomization (after previous 48h with Biphozyl®); 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.
Experimental: Biphozyl®	Drug: CVVH with Biphozyl® in the first 48h after randomization; 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.; Drug: CVVH with Biphozyl® in the second 48h after randomization (after previous 48h with Phoxilium®); 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.

What is the study measuring?

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®)

Collaborators and Investigators

• Sponsor: Medical University Innsbruck
• Investigators: Principal Investigator: Michael Joannidis, Univ.-Prof., MD, Medical University Innsbruck

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2020
• Primary Completion (Actual): November 15, 2023
• Study Completion (Actual): March 11, 2024

Study Registration Dates

• First Submitted: August 23, 2019
• First Submitted That Met QC Criteria: August 26, 2019
• First Posted (Actual): August 28, 2019

Study Record Updates

• Last Update Posted (Actual): March 13, 2024
• Last Update Submitted That Met QC Criteria: March 12, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Kidney Diseases; Urologic Diseases; Disease Attributes; Renal Insufficiency; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Critical Illness; Acute Kidney Injury
• Other Study ID Numbers: EudraCT No. 2019-001262-15

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No