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.
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
Known shellfish allergy
Moribund status with life expectancy too low to benefit
Concurrent participation in another interventional study
Exclusion period defined by another study
Crossover
Continuous veino-veinous dialysis with iron-chelator supplemented dialysate
Combination productParticipants 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
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.
24-hour serum iron clearance
24-hour serum iron clearance with iron chelation by addition of MEX-CD1 to the dialysate.
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.
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.
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.
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.
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.
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."
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.
Click on the lead sponsor to view all of their trials.
