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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Phoxilium® | Active Comparator |
| |
| Biphozyl® | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| 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®) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Michael Joannidis, Univ.-Prof., MD | Medical University Innsbruck | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Division of Intensive Care and Emergency Medicine, Department of Internal Medicine, Medical University Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria | Innsbruck | Tyrol | 6020 | Austria |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41247497 | Derived | 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. | |
| 40759107 |
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|
| 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. |
|
| 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. |
|
| 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. |
| ID | Term |
|---|---|
| D016638 | Critical Illness |
| D058186 | Acute Kidney Injury |
| ID | Term |
|---|---|
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D051437 | Renal Insufficiency |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
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