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

NCT07236463 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: NIMAO/2023-1/SB-01
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Sepsis; Acute Kidney Injury

Keywords

Acute Kidney Injury; Sepsis; Continuous Renal Replacement Therapy; Iron Chelating Agents; Intensive Care Unit

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• 24-hour serum iron clearance

  48 hours

• ratio iron clearance/creatinine clearance

  48 hours

• Plasma malondialdehyde concentration

  From enrollment until the end of the intervention at 48 hours.

• Plasma Thiobarbituric Acid Reactive Substances (TBARS)

  From enrollment until the end of the intervention at 48 hours.

• Plasma protein thiols

  From enrollment until the end of the intervention at 48 hours.

Other Outcomes (11)

• Number of participants with potentially treatment-related adverse events, as assessed by CTCAE v6.0, during the intervention.

  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.

  From the end of the intervention at Hour 48 until Day 28 or ICU discharge, whichever occurs first

• Serum iron levels

  28 Days

Study Arms (2)

Sequence A: MEX-CD1-supplemented dialysate first, then standard dialysate

OTHER

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

Sequence B: Standard dialysate first, then MEX-CD1-supplemented dialysate

OTHER

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

Interventions

Continuous veino-veinous dialysis with iron-chelator supplemented dialysate COMBINATION_PRODUCT

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

Sequence A: MEX-CD1-supplemented dialysate first, then standard dialysate; Sequence B: Standard dialysate first, then MEX-CD1-supplemented dialysate

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• Centre Hospitalier Universitaire de Nīmes: lead

Study Sites (1)

Nimes University Hospital

Nîmes, Gard, 30000, France

Location

Related Publications (3)

• 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.

  PMID: 38049866 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.

  PMID: 34620952 BACKGROUND

• 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.

  PMID: 41436269 DERIVED

MeSH Terms

Conditions

Acute Kidney Injury; Sepsis

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Saber D BARBAR, MD, PhD

  Centre Hospitalier Universitaire de Nīmes

  PRINCIPAL INVESTIGATOR

Central Study Contacts

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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. * Sequence A: MEX-CD1-supplemented dialysate first, then standard dialysate * Sequence B: Standard dialysate first, then MEX-CD1-supplemented dialysate

Study Record Dates

• First Submitted: August 21, 2025
• First Posted: November 19, 2025
• Study Start: February 1, 2026
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): May 1, 2028
• Last Updated: January 22, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)