Development of an Innovative Hemodialysis Method to Improve Dialytic Clearance of Protein-bound Uremic Toxins

Обзор

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%).

Вмешательства

• Препарат Medialipide 20% perfusion
  Each patient will receive during a 4 hours hemodialysis session a perfusion of Medialipide 20% at a rate of 0,11 g/kg/h. Medialipide will be perfused using the venous line connected to the hemodialysis machine.
• Препарат NaCl 0,9%
  Each patient will receive during a 4 hours hemodialysis session a perfusion of NACL 0,9% with a volume corresponding to the one of Medialipide 20%. NaCl 0,9% will be perfused using the venous line connected to the hemodialysis machine.
• Биопрепарат Blood sample
  Serial biological sampling for the measurement of different blood concentrations : electrolytes, serum protein , albumin, renal function (urea, creatinine), hemoglobin, hematocrit, liver test, lipid test, ketone bodies, 6 uremic toxins (including IS and p-CS), sodium octanoate and decanoate.

Первичные конечные точки

• Dialytic clearance of p-CS [Срок оценки: until 240 minutes after haemodialysis session]

Вторичные конечные точки (12)

• Reduction fraction (RF) of p-CS [Срок оценки: At 240 minutes after haemodialysis session]
• Dialytic clearance of Indoxyl sulfate [Срок оценки: until 240 minutes after haemodialysis session]
• Reduction fraction (RF) of Indoxyl sulfate [Срок оценки: At 240 minutes after haemodialysis session]
• Dialytic clearance of hippuric acid [Срок оценки: until 240 minutes after haemodialysis session]
• Reduction fraction (RF) of hippuric acid [Срок оценки: At 240 minutes after haemodialysis session]
• Dialytic clearance of p-cresyl glucuronide [Срок оценки: until 240 minutes after haemodialysis session]
• Reduction fraction (RF) of p-cresyl glucuronide [Срок оценки: At 240 minutes after haemodialysis session]
• Dialytic clearance of indol acetic acid [Срок оценки: until 240 minutes after haemodialysis session]
• Reduction fraction (RF) of indol acetic acid [Срок оценки: At 240 minutes after haemodialysis session]
• Dialytic clearance of uric acid [Срок оценки: until 240 minutes after haemodialysis session]
• Reduction fraction (RF) of uric acid [Срок оценки: At 240 minutes after haemodialysis session]
• Dialytic clearance of 3-Carboxy-4-methyl-5-propyl-2-furanpropionic acid [Срок оценки: until 240 minutes after haemodialysis session]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Перекрёстный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Франция · 1 центр

• Hopital Edouard Herriot — Lyon

Идентификаторы

NCT: NCT06595680 · 69HCL23_0031 · 2023-510406-41-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗