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The goal of this clinical trial is to learn if adding the iron-binding drug MEX-CD1 to dialysis fluid can help remove excess iron in adults with sepsis-associated acute kidney injury (AKI) requiring dialysis who are in the intensive care unit (ICU). The main questions it aims to answer are:
Does adding MEX-CD1 to the dialysis fluid increase the amount of iron removed during dialysis? Is using MEX-CD1 in dialysis fluid safe for patients?
Participants will:
Be adults in the ICU with sepsis-associated AKI who need continuous dialysis (renal replacement therapy) Receive two 24-hour dialysis sessions: one with standard dialysis fluid and one with dialysis fluid containing MEX-CD1 Serve as their own control, meaning they will receive both treatments
Researchers will measure:
The amount of iron removed in the dialysis waste fluid (primary outcome) Blood levels of iron Changes in other trace elements Markers of inflammation and oxidative stress Safety outcomes up to 28 days after treatment This is a pilot study being done at a single hospital in France.
Sepsis-associated acute kidney injury (AKI) is a common and serious complication in critically ill patients admitted to intensive care units (ICUs). It is associated with high rates of death and long-term health problems. Currently, there is no specific treatment to address the underlying causes of this condition beyond supportive measures such as dialysis to replace kidney function.
A growing body of research suggests that excess circulating labile (easily reactive) iron plays an important role in the development of organ injury during sepsis. Labile iron can promote oxidative stress, mitochondrial damage, and cell death through a process called ferroptosis. Reducing the amount of labile iron in the bloodstream may help limit these harmful effects.
This study is designed to evaluate a new approach to lowering labile iron levels during continuous renal replacement therapy (CRRT) in patients with sepsis-associated AKI. The investigational strategy uses an iron-binding compound (iron chelator) called MEX-CD1 added to the dialysis fluid (dialysate) during continuous veno-venous hemodialysis (CVVHD). By binding iron in the dialysis circuit, the chelator aims to enhance the removal of labile iron from the patient's blood without requiring systemic administration of the chelating agent.
This is a single-centre, randomised, open-label, two-period crossover phase I-II pilot study conducted in the ICU of Nîmes University Hospital in France. Each participant will undergo two consecutive 24-hour sessions of CVVHD, one using standard dialysate and one using dialysate supplemented with MEX-CD1 at a concentration of 50 mg/L. The order of the sessions will be randomised so that each participant serves as their own control, helping to reduce variability due to individual differences in illness severity or metabolism.
The primary objective of the study is to assess the performance of iron removal by measuring the concentration of iron in the dialysis effluent. Secondary objectives include evaluating plasma iron clearance, monitoring for loss of other trace elements, and assessing biomarkers related to oxidative stress and inflammation. Safety outcomes will also be closely monitored during the dialysis sessions and for 28 days afterward, including any adverse events related to the use of MEX-CD1 in the dialysate.
This pilot study will generate preliminary data on the feasibility, safety, and potential effectiveness of this novel dialysis-based iron removal strategy. If successful, it may support the development of larger trials aimed at improving outcomes for critically ill patients with sepsis-associated AKI.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sequence A: MEX-CD1-supplemented dialysate first, then standard dialysate | Other | Participants will receive two consecutive 24-hour CVVHD sessions using:
|
|
| Sequence B: Standard dialysate first, then MEX-CD1-supplemented dialysate | Other | Participants will receive two consecutive 24-hour CVVHD sessions using:
|
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Continuous veino-veinous dialysis with iron-chelator supplemented dialysate | Combination Product | Participants will receive two consecutive 24-hour CVVHD sessions using:
Both sessions will use identical RRT parameters, no dose escalation is planned:
|
| Measure | Description | Time Frame |
|---|---|---|
| Free iron concentrations in the dialysis effluent | The primary outcome is defined as the comparison of free iron concentrations in the effluent collected during 24-hour dialysis sessions performed under two conditions: using standard dialysate and using dialysate supplemented with the iron chelator MEX-CD1. | 48 hours (2 consecutive sessions of 24 hours CVVHD) |
| Measure | Description | Time Frame |
|---|---|---|
| 24-hour serum iron clearance | 24-hour serum iron clearance with iron chelation by addition of MEX-CD1 to the dialysate. | 48 hours |
| ratio iron clearance/creatinine clearance | Compare the ratio of 24-hour plasma iron clearance to creatinine clearance between standard dialysate and MEX-CD1-supplemented dialysate. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of participants with potentially treatment-related adverse events, as assessed by CTCAE v6.0, during the intervention. | Safety will be assessed by the incidence of potentially treatment-related adverse events during the first 48 hours of renal replacement therapy with standard dialysate or dialysate supplemented with MEX-CD1, including hypotension, cutaneous erythema, and other non-prespecified events, classified according to CTCAE v6.0. |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Saber D BARBAR, MD, PhD | Contact | 0033466683320 | saber.barbar@chu-nimes.fr | |
| Jean-Yves LEFRANT, MD, PhD | Contact | 0033466683320 | jean-yves.lefrant@chu-nimes.fr |
| Name | Affiliation | Role |
|---|---|---|
| Saber D BARBAR, MD, PhD | Centre Hospitalier Universitaire de Nīmes | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Nimes University Hospital | Not yet recruiting | Nîmes | Gard | 30000 | France | |
| CHU de Nîmes |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38049866 | Background | Grange C, Lux F, Brichart T, David L, Couturier A, Leaf DE, Allaouchiche B, Tillement O. Iron as an emerging therapeutic target in critically ill patients. Crit Care. 2023 Dec 4;27(1):475. doi: 10.1186/s13054-023-04759-1. | |
| 34620952 | Background | Natuzzi M, Grange C, Grea T, Brichart T, Aigle A, Bechet D, Hautefeuille B, Thomas E, Ayoub JY, Bonnet JM, Louzier V, Allaouchiche B, Couturier A, Montembault A, de Oliveira PN, David L, Lux F, Tillement O. Feasibility study and direct extraction of endogenous free metallic cations combining hemodialysis and chelating polymer. Sci Rep. 2021 Oct 7;11(1):19948. doi: 10.1038/s41598-021-99462-y. |
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Participants will be randomized in a 1:1 ratio to one of two treatment sequences using a computer-generated, block-randomized list prepared by an independent statistician.
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|
| 48 hours |
| Plasma malondialdehyde concentration | The impact of iron chelation, achieved by adding MEX-CD1 to the dialysate, will be assessed on oxidative stress biomarkers by measuring plasma malondialdehyde concentrations every 8 hours for 48 hours. | From enrollment until the end of the intervention at 48 hours. |
| Plasma Thiobarbituric Acid Reactive Substances (TBARS) | The impact of iron chelation, achieved by adding MEX-CD1 to the dialysate, will be assessed on oxidative stress biomarkers by measuring Plasma Thiobarbituric Acid Reactive Substances (TBARS) concentrations every 8 hours for 48 hours. | From enrollment until the end of the intervention at 48 hours. |
| Plasma protein thiols | The impact of iron chelation, achieved by adding MEX-CD1 to the dialysate, will be assessed on oxidative stress biomarkers by measuring plasma protein thiol concentrations every 8 hours for 48 hours. | From enrollment until the end of the intervention at 48 hours. |
| Plasma Glutathione Peroxidase (GPx) concentration | The impact of iron chelation, achieved by adding MEX-CD1 to the dialysate, will be assessed on oxidative stress biomarkers by measuring plasma Glutathione Peroxidase (GPx) concentrations every 8 hours for 48 hours. | From enrollment until the end of the intervention at 48 hours. |
| Plasma C-reactive protein levels | The impact of iron chelation, achieved by adding MEX-CD1 to the dialysate, will be assessed on inflammatory biomarkers by measuring plasma C-reactive protein levels every 8 hours for 48 hours. | From enrollment until the end of the intervention at 48 hours. |
| Plasma procalcitonin levels | The impact of iron chelation, achieved by adding MEX-CD1 to the dialysate, will be assessed on inflammatory biomarkers by measuring plasma procalcitonin levels every 8 hours for 48 hours. | From enrollment until the end of the intervention at 48 hours. |
| From enrollment until the end of the intervention at 48 hours. |
| Number of participants with potentially treatment-related adverse events, as assessed by CTCAE v6.0, after the intervention. | Long-term safety will be assessed by the incidence of potentially treatment-related adverse events occurring after the first 48 hours of the intervention (renal replacement therapy with standard dialysate or dialysate supplemented with MEX-CD1) and up to day 28, including anemia, low serum iron levels, and other non-prespecified events, classified according to CTCAE v6.0. | From the end of the intervention at Hour 48 until Day 28 or ICU discharge, whichever occurs first |
| Serum iron levels | the investigators will evaluate the impact of iron chelation (by adding MEX-CD1 to the dialysate) on iron balance up to Day 28. Serum iron will be measured at Day 0, Day 1, Day 2, Day 7, and Day 28." | 28 Days |
| Serum transferrin levels | the investigators will evaluate the impact of iron chelation (by adding MEX-CD1 to the dialysate) on iron metabolism markers up to Day 28. Serum transferrin levels will be measured at Day 0, Day 1, Day 2, Day 7, and Day 28. | 28 days |
| Serum ferritin levels | the investigators will evaluate the impact of iron chelation (by adding MEX-CD1 to the dialysate) on iron metabolism markers up to Day 28. Serum ferritin levels will be measured at Day 0, Day 1, Day 2, Day 7, and Day 28. | 28 days |
| Serum soluble transferrin receptor (sTfR) levels | the investigators will evaluate the impact of iron chelation (by adding MEX-CD1 to the dialysate) on iron metabolism markers up to Day 28. Serum soluble transferrin receptor (sTfR) levels will be measured at Day 0, Day 1, Day 2, Day 7, and Day 28. | 28 days |
| Serum hepcidin levels | the investigators will evaluate the impact of iron chelation (by adding MEX-CD1 to the dialysate) on iron metabolism markers up to Day 28. Serum hepcidin levels will be measured at Day 0, Day 1, Day 2, Day 7, and Day 28. | 28 days |
| 24-hour copper clearance | Measurement of 24-hour copper clearance after a dialysis session with MEX-CD1 added to the dialysate or with standard dialysate. Copper clearance will be calculated as: (effluent copper concentration × effluent volume over 24 hours) / serum copper concentration. | 48 hours |
| 24-hour selenium clearance | Measurement of 24-hour selenium clearance after a dialysis session with MEX-CD1 added to the dialysate or with standard dialysate. Selenium clearance will be calculated as: (effluent selenium concentration × effluent volume over 24 hours) / serum selenium concentration. | 48 hours |
| 24-hour plasma zinc clearance | Measurement of 24-hour zinc clearance after a dialysis session with MEX-CD1 added to the dialysate or with standard dialysate. Zinc clearance will be calculated as: (effluent zinc concentration × effluent volume over 24 hours) / serum zinc concentration. | 48 hours |
| 24-hour aluminium clearance | Measurement of 24-hour aluminium clearance after a dialysis session with MEX-CD1 added to the dialysate or with standard dialysate. Aluminium clearance will be calculated as: (effluent aluminium concentration × effluent volume over 24 hours) / serum aluminium concentration. | 48 hours |
| Recruiting |
| Nîmes |
| 30029 |
| France |
|
| 41436269 | Derived | Couturier A, Serrand C, Masseguin C, Allaouchiche B, Tillement O, Lefrant JY, Barbar SD. Evaluation of the performance and safety of adding the iron chelator MEX-CD1 to dialysate during continuous veno-venous haemodialysis for removing excess labile iron in intensive care patients with sepsis-associated acute kidney injury - the Iron in Intensive Care trial (IRON-I.C.): protocol for a phase I-II randomised crossover pilot study. BMJ Open. 2025 Dec 23;15(12):e109783. doi: 10.1136/bmjopen-2025-109783. |
| ID | Term |
|---|---|
| D058186 | Acute Kidney Injury |
| D018805 | Sepsis |
| ID | Term |
|---|---|
| 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 |
| D007239 | Infections |
| D018746 | Systemic Inflammatory Response Syndrome |
| D007249 | Inflammation |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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