Labile Iron Removal by Adding the Iron Chelator MEX-CD1 to Dialysate in Sepsis-Associated Acute Kidney Injury (IRON-IC)

Performance and Safety of Labile Iron Removal by Adding the Iron Chelator MEX-CD1 to Dialysate During Continuous Veno-venous Hemodialysis for Sepsis-associated AKI: Protocol for a Phase I-II Randomized Crossover Pilot Study.

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Sepsis; Acute Kidney Injury
• Intervention / Treatment: Combination product: Continuous veino-veinous dialysis with iron-chelator supplemented dialysate

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 14
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Saber D BARBAR, MD, PhD; Phone Number: 0033466683320; Email: saber.barbar@chu-nimes.fr
• Study Contact Backup: Name: Jean-Yves LEFRANT, MD, PhD; Phone Number: 0033466683320; Email: jean-yves.lefrant@chu-nimes.fr

Study Locations

• France
  • Gard
    • Nîmes, Gard, France, 30000
      • Nîmes University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adult patients (≥18 years) admitted to ICU with sepsis-associated AKI requiring CRRT
• Sepsis defined according to SEPSIS-3 criteria (suspected/documented infection with organ dysfunction indicated by ≥2-point increase in SOFA [Sequential Organ Failure Assessment] score)
• AKI Stage 3 per KDIGO (Kidney Disease: Improving Global Outcomes) criteria: acute rise in serum creatinine ≥3 times baseline or serum creatinine ≥4 mg/dL or urine output <0.3 mL/kg/h for ≥24 hours or anuria (urine output <100ml) for ≥12 hours
• Indications for CRRT: refractory hyperkalemia (>6 mmol/L) or refractory metabolic acidosis (pH < 7.20) or acute pulmonary edema unresponsive to medical management or urine output <0.3 ml/kg/hour or anuria (urine output <100ml) persistent for 48 hours and refractory to medical treatment
• Informed consent obtained from patient or legal representative
• Affiliated with or beneficiary of a health insurance plan

Exclusion Criteria:

• Known shellfish allergy
• Moribund status with life expectancy too low to benefit
• Concurrent participation in another interventional study
• Exclusion period defined by another study
• Under legal protection (guardianship or curatorship)
• Inability to obtain informed consent from patient or representative
• Pregnant, parturient, or breastfeeding women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Sequence A: MEX-CD1-supplemented dialysate first, then standard dialysate; Participants will receive two consecutive 24-hour CVVHD sessions using: Standard Dialysate: Commercially available CiCa™ dialysate (Fresenius Medical Care, Germany); MEX-CD1 Dialysate: CiCa™ dialysate supplemented with MEX-CD1 at 50 mg/L (28). MEX-CD1 remains confined to the dialysate, separated from the patient's circulation by the dialysis membrane because of its molecular weight	Combination product: Continuous veino-veinous dialysis with iron-chelator supplemented dialysate; Participants will receive two consecutive 24-hour CVVHD sessions using: Standard Dialysate: Commercially available CiCa™ dialysate (Fresenius Medical Care, Germany); MEX-CD1 Dialysate: CiCa™ dialysate supplemented with MEX-CD1 at 50 mg/L (28). MEX-CD1 remains confined to the dialysate, separated from the patient's circulation by the dialysis membrane because of its molecular weight Both sessions will use identical RRT parameters, no dose escalation is planned: Continuous veno-venous hemodialysis (CVVHD) modality; Multifiltrate™ dialyzer (Fresenius Medical Care, Germany) with regional citrate anticoagulation; Dialysis dose of 20-25 mL/kg/h (approx. 1600 mL/h dialysate flow); Blood flow 80 mL/min; Ultrasound-guided placement of a 15 cm 16 F double-lumen catheter in the right internal jugular vein; The circuit and the dialysis filter will be changed after each 24 hours CVVHD session
Other: Sequence B: Standard dialysate first, then MEX-CD1-supplemented dialysate; Participants will receive two consecutive 24-hour CVVHD sessions using: Standard Dialysate: Commercially available CiCa™ dialysate (Fresenius Medical Care, Germany); MEX-CD1 Dialysate: CiCa™ dialysate supplemented with MEX-CD1 at 50 mg/L (28). MEX-CD1 remains confined to the dialysate, separated from the patient's circulation by the dialysis membrane because of its molecular weight	Combination product: Continuous veino-veinous dialysis with iron-chelator supplemented dialysate; Participants will receive two consecutive 24-hour CVVHD sessions using: Standard Dialysate: Commercially available CiCa™ dialysate (Fresenius Medical Care, Germany); MEX-CD1 Dialysate: CiCa™ dialysate supplemented with MEX-CD1 at 50 mg/L (28). MEX-CD1 remains confined to the dialysate, separated from the patient's circulation by the dialysis membrane because of its molecular weight Both sessions will use identical RRT parameters, no dose escalation is planned: Continuous veno-venous hemodialysis (CVVHD) modality; Multifiltrate™ dialyzer (Fresenius Medical Care, Germany) with regional citrate anticoagulation; Dialysis dose of 20-25 mL/kg/h (approx. 1600 mL/h dialysate flow); Blood flow 80 mL/min; Ultrasound-guided placement of a 15 cm 16 F double-lumen catheter in the right internal jugular vein; The circuit and the dialysis filter will be changed after each 24 hours CVVHD session

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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)

Secondary Outcome Measures

Outcome Measure	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.	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.

Other Outcome Measures

Outcome Measure	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.	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
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
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

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Nīmes
• Investigators: Principal Investigator: Saber D BARBAR, MD, PhD, Centre Hospitalier Universitaire de Nīmes

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2026
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): May 1, 2028

Study Registration Dates

• First Submitted: August 21, 2025
• First Submitted That Met QC Criteria: November 14, 2025
• First Posted (Actual): November 19, 2025

Study Record Updates

• Last Update Posted (Actual): January 22, 2026
• Last Update Submitted That Met QC Criteria: January 21, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Intensive Care Unit; Sepsis; Acute Kidney Injury; Continuous Renal Replacement Therapy; Iron Chelating Agents
• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Renal Insufficiency; Pathological Conditions, Signs and Symptoms; Acute Kidney Injury; Sepsis
• Other Study ID Numbers: NIMAO/2023-1/SB-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No