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.
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 14
- 试验地点
- 3
- 主要终点
- Free iron concentrations in the dialysis effluent
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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
干预措施: Continuous veino-veinous dialysis with iron-chelator supplemented dialysate (Combination Product)
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
干预措施: Continuous veino-veinous dialysis with iron-chelator supplemented dialysate (Combination Product)
结局指标
主要结局
Free iron concentrations in the dialysis effluent
时间窗: 48 hours (2 consecutive sessions of 24 hours CVVHD)
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.
次要结局
- 24-hour serum iron 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.)
- ratio iron clearance/creatinine clearance(48 hours)
- Plasma protein thiols(From enrollment until the end of the intervention at 48 hours.)
- Plasma procalcitonin levels(From enrollment until the end of the intervention at 48 hours.)
- Plasma Glutathione Peroxidase (GPx) concentration(From enrollment until the end of the intervention at 48 hours.)
- Plasma C-reactive protein levels(From enrollment until the end of the intervention at 48 hours.)