Development of an Innovative Hemodialysis Method to Improve Dialytic Clearance of Protein-bound Uremic Toxins
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Dialytic clearance of p-CS
研究概览
简要总结
Current hemodialysis techniques fail to efficiently remove protein-bound uremic toxins (such as p-cresyl sulfate (p-CS) or indoxyl sulfate (IS)) due to their strong binding to serum albumin. The accumulation of these toxins in end-stage renal failure patients on hemodialysis is strongly suspected to contribute to the significant morbidity and mortality observed in this population.
Pre-clinical studies conducted previously showed that medium-chain fatty acids (such as sodium octanoate and decanoate), which are natural ligands of albumin, can effectively displace the binding of uremic toxins on serum albumin and thus promote their elimination during a hemodialysis session.
Medialipide® 20% (Braun) is an emulsion of medium chain triglycerides (MCT) (6 to 12 carbons) used in parenteral nutrition. Medialipide® constitutes a relevant clinical formulation for the administration of octanoate and decanoate because it contains 94% of sodium octanoate and decanoate.
In this study, a proof of concept intervention will be carried out to study the effect on the clearance uremic toxins clearance of the perfusion of Medialipide® emulsion (as a sodium octanoate and decanoate donor) in patients during their hemodialysis session compared to a control situation Sodium chloride (NaCl) 0,9%).
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
- None
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
- •Age ≥18 years
- •On haemodialysis at a frequency of 3 sessions of 4 hours per week, for at least 3 months.
- •For patients of childbearing age, effective contraception (sexual abstinence, hormonal contraception, intrauterine device or hormone-releasing system, cap, diaphragm or sponge with spermicide, condom) for the entire duration of treatment is required. A blood pregnancy test (beta-human chorionic gonadotropin (HCG)) will be carried out at inclusion.
- •Patient affiliated to a social security scheme
- •Free, informed and written consent signed by the patient
排除标准
- •Residual diuresis > 100 mL per day
- •Pregnant or breast-feeding
- •Uncontrolled hypertension > 180/115 millimetre of mercury (mmHg)
- •Perdialytic hypotension requiring vascular filling > 100 mL during the last 3 sessions
- •Patients already on parenteral nutrition
- •Patients already on Vitamin K antagonists (VKA) (or prescribed less than one month before inclusion)
- •Patients with allergy to heparin or requiring haemodialysis without anticoagulant (recent haemorrhage)
- •Criteria relating to products/procedures: Patient with
- •an allergy to egg, soya or peanut proteins or to one of the active ingredients or one of the excipients (glycerol, egg phospholipids for injection, a-tocopherol, sodium oleate (to adjust the pH), water for injection) of Médialipide
- •Severe hyperlipidaemia or severe lipid metabolism disorder characterised by hypertriglyceridaemia > 3 mmol/l
- •Sepsis < 1 month
- •Severe liver failure or cholestasis
- •Known severe coagulopathy
- •Acute thrombo-embolic events
- •Fat embolism
- •Aggravating bleeding diathesis,
- •Uncompensated metabolic acidosis.
- •Unstable circulatory state threatening the vital prognosis (collapse and shock),
- •Unstable metabolic conditions (e.g. severe post-traumatic syndrome, coma of unknown origin),
- •Acute phase of myocardial infarction or stroke,
- •Uncorrected disturbances of fluid and electrolyte balance, such as hypokalaemia and hypotonic dehydration.
- •Decompensated heart failure,
- •Acute pulmonary oedema.
- •Subject participating in another interventional study involving a drug with an exclusion period still in progress at inclusion.
研究组 & 干预措施
Medialipide 20% - NaCl 0,9%
Group 1 will receive during the first interventional hemodialysis session a perfusion of Medialipide 20% perfused at a rate of 0,11 gram/kilogram/hour (g/kg/h) during 4 hours. One week late, they will receive during the second interventional hemodialysis session a perfusion of NaCl 0,9% with a volume corresponding to the one of Medialipide also during 4 hours.
干预措施: Medialipide 20% perfusion (Drug)
Medialipide 20% - NaCl 0,9%
Group 1 will receive during the first interventional hemodialysis session a perfusion of Medialipide 20% perfused at a rate of 0,11 gram/kilogram/hour (g/kg/h) during 4 hours. One week late, they will receive during the second interventional hemodialysis session a perfusion of NaCl 0,9% with a volume corresponding to the one of Medialipide also during 4 hours.
干预措施: NaCl 0,9% (Drug)
Medialipide 20% - NaCl 0,9%
Group 1 will receive during the first interventional hemodialysis session a perfusion of Medialipide 20% perfused at a rate of 0,11 gram/kilogram/hour (g/kg/h) during 4 hours. One week late, they will receive during the second interventional hemodialysis session a perfusion of NaCl 0,9% with a volume corresponding to the one of Medialipide also during 4 hours.
干预措施: Blood sample (Biological)
NaCl 0,9% - Medialipide 20%
Group 2 will receive during the first interventional hemodialysis session a perfusion of NaCl 0,9% with a volume corresponding to the one of Medialipide during 4 hours. One week late, they will receive during the second interventional hemodialysis session a perfusion of Medialipide 20% perfused at a rate of 0,11 gram/kilogram/hour (g/kg/h) also during 4 hours.
干预措施: Medialipide 20% perfusion (Drug)
NaCl 0,9% - Medialipide 20%
Group 2 will receive during the first interventional hemodialysis session a perfusion of NaCl 0,9% with a volume corresponding to the one of Medialipide during 4 hours. One week late, they will receive during the second interventional hemodialysis session a perfusion of Medialipide 20% perfused at a rate of 0,11 gram/kilogram/hour (g/kg/h) also during 4 hours.
干预措施: NaCl 0,9% (Drug)
NaCl 0,9% - Medialipide 20%
Group 2 will receive during the first interventional hemodialysis session a perfusion of NaCl 0,9% with a volume corresponding to the one of Medialipide during 4 hours. One week late, they will receive during the second interventional hemodialysis session a perfusion of Medialipide 20% perfused at a rate of 0,11 gram/kilogram/hour (g/kg/h) also during 4 hours.
干预措施: Blood sample (Biological)
结局指标
主要结局
Dialytic clearance of p-CS
时间窗: until 240 minutes after haemodialysis session
Dialysis clearance of p-CS (millilitre/minute) is defined as follows: Clearance = Qd X (C dialysate/C arterial) with Qd corresponding to the dialysate flow rate, C dialysate the concentration of p-CS in the dialysate, C arterial the concentration of p-CS in the blood sampled at the arterial port of the dialyser.
次要结局
- Reduction fraction (RF) of p-CS(At 240 minutes after haemodialysis session)
- Dialytic clearance of Indoxyl sulfate(until 240 minutes after haemodialysis session)
- Reduction fraction (RF) of Indoxyl sulfate(At 240 minutes after haemodialysis session)
- Dialytic clearance of hippuric acid(until 240 minutes after haemodialysis session)
- Reduction fraction (RF) of hippuric acid(At 240 minutes after haemodialysis session)
- Dialytic clearance of p-cresyl glucuronide(until 240 minutes after haemodialysis session)
- Reduction fraction (RF) of p-cresyl glucuronide(At 240 minutes after haemodialysis session)
- Dialytic clearance of indol acetic acid(until 240 minutes after haemodialysis session)
- Reduction fraction (RF) of indol acetic acid(At 240 minutes after haemodialysis session)
- Dialytic clearance of uric acid(until 240 minutes after haemodialysis session)
- Reduction fraction (RF) of uric acid(At 240 minutes after haemodialysis session)
- Dialytic clearance of 3-Carboxy-4-methyl-5-propyl-2-furanpropionic acid(until 240 minutes after haemodialysis session)
- Reduction fraction (RF) of 3-Carboxy-4-methyl-5-propyl-2-furanpropionic acid(At 240 minutes after haemodialysis session)
- Tolerance of medialipide perfusion (%)(until 240 minutes after haemodialysis session)
- octanoate blood concentration(until 240 minutes after haemodialysis session)
- Safety of medialipide perfusion(until 7 days after the last haemodialysis session)
- decanoate blood concentration(until 240 minutes after haemodialysis session)
- clearance of octanoate(until 240 minutes after haemodialysis session)
- clearance of decanoate(until 240 minutes after haemodialysis session)