Critically IllPhase 2NCT04071171
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 Phase 2 study testing CVVH with Phoxilium® in the first 48h after randomization, CVVH with Biphozyl® in the first 48h after randomization and CVVH with Phoxilium® in the second 48h after randomization (after previous 48h with Biphozyl®) in people with Critically Ill and Acute Kidney Injury, run by Medical University Innsbruck at 1 site in Austria.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Critically Ill, Acute Kidney Injury, Renal Replacement Therapy
- What is being tested?
- CVVH with Phoxilium® in the first 48h after randomization, CVVH with Biphozyl® in the first 48h after randomization and CVVH with Phoxilium® in the second 48h after randomization (after previous 48h with Biphozyl®)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 88 participants
- Where
- 1 siteAustria
- Study dates
- 1 Aug 2020to 11 Mar 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
Trial locations and contacts
1 site in 1 country.
Austria1 site
Division of Intensive Care and Emergency Medicine, Department of Internal Medicine, Medical University Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria
Innsbruck, Tyrol, 6020
About this study
Official title: 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.
Read the 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.
- Conditions
- Critically Ill, Acute Kidney Injury, Renal Replacement Therapy, Continuous Renal Replacement Therapy, Continuous Veno-Venous Hemofiltration, Replacement Fluid
- Being tested
- CVVH with Phoxilium® in the first 48h after randomization, CVVH with Biphozyl® in the first 48h after randomization, CVVH with Phoxilium® in the second 48h after randomization (after previous 48h with Biphozyl®), CVVH with Biphozyl® in the second 48h after randomization (after previous 48h with Phoxilium®)
- Medical subject headings
- Critical Illness, Acute Kidney Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CVVH with Phoxilium® in the first 48h after randomizationDrug
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.
CVVH with Biphozyl® in the first 48h after randomizationDrug
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.
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.
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.
| Study group | Role | What they receive |
|---|---|---|
| Phoxilium® | Active comparator | Not described Receives: 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 | Not described Receives: 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®) |
What is being measured
The primary outcome is the main question the study is designed to answer.
pH
Rate of pH excursions from a set range of 7.35-7.45.
Measured: 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.
Measured: 96 hours (48h of CVVH with Phoxilium® vs. 48h of CVVH with Biphozyl®)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Aug 2019
- Study start1 Aug 2020
- Primary completion15 Nov 2023
- Study completion11 Mar 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Critically IllStudies of the same condition, open and under way.
- More trials run by Medical University InnsbruckThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 88 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical University Innsbruck
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Michael Joannidis, Univ.-Prof., MD, Principal investigator, Medical University Innsbruck
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04071171
- Sponsor's protocol ID
- EudraCT No. 2019-001262-15
- Status last verified
- Mar 2024
- First submitted
- 23 Aug 2019
- Last updated
- 13 Mar 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 41247497Koglberger 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.
PubMed 40759107
Study at a glance
From the registry record, last updated by the sponsor on 13 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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]
- ClinicalTrials.gov ID
- NCT04071171
- Acronym / sponsor ID
- EudraCT No. 2019-001262-15
- Conditions
- Critically Ill, Acute Kidney Injury, Renal Replacement Therapy, Continuous Renal Replacement Therapy, Continuous Veno-Venous Hemofiltration, Replacement Fluid
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 88 participants (actual)
- Lead sponsor
- Medical University InnsbruckUniversity, hospital or other
- Study start
- 1 Aug 2020 (actual)
- Primary completion
- 15 Nov 2023 (actual)
- Study completion
- 11 Mar 2024 (actual)
- First posted
- 28 Aug 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 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®) |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CVVH with Phoxilium® in the first 48h after randomizationAfter 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 | Phoxilium® |
| CVVH with Biphozyl® in the first 48h after randomizationAfter 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 | Biphozyl® |
| 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. | Drug | Phoxilium® |
| 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. | Drug | Biphozyl® |
Primary outcome
pH
Time frame: 96 hours (48h of CVVH with Phoxilium® vs. 48h of CVVH with Biphozyl®)
Rate of pH excursions from a set range of 7.35-7.45.
HCO3-
Time frame: 96 hours (48h of CVVH with Phoxilium® vs. 48h of CVVH with Biphozyl®)
Rate of HCO3- excursions from a set range of 22-26 mmol/l.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Mar 2024.
- Derived from this study: PubMed 41247497Perschinka 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.
- Derived from this study: PubMed 40759107Koglberger 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael Joannidis, Univ.-Prof., MD principal investigator
Medical University Innsbruck
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing CVVH with Phoxilium® in the first 48h after randomization, CVVH with Biphozyl® in the first 48h after randomization and CVVH with Phoxilium® in the second 48h after randomization (after previous 48h with Biphozyl®) in people with Critically Ill and Acute Kidney Injury, run by Medical University Innsbruck at 1 site in Austria.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Austria. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
pH (time frame: 96 hours (48h of CVVH with Phoxilium® vs. 48h of CVVH with Biphozyl®)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04071171, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Mar 2024.