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

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.

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.

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