Daily Versus Alternate Day Plasma Exchange in Wilson Disease With Acute Liver Failure in Children

Официальное название

Daily Versus Alternate Day Plasma Exchange in Wilson Disease With Acute Liver Failure in Children: A Randomized Controlled Trial

Обзор

Wilson disease in children has a varied presentation. Wilson disease with acute liver failure is associated with very high mortality and morbidity. The standard therapy i.e chelation (with either D- penicillamine or trientene can be used as a temporizing agent to treat the enormous release of copper into the blood stream; however, substantial removal is not achieved for at least 1 to 3 months. Plasma exchange provides a means of rapid means of removal of copper. As per American Society for Apheresis, TPE in wilson disease with acute liver failure can rapidly remove an average of 20 mg of copper per TPE treatment. Decreased serum copper may decrease hemolysis, prevent progression of kidney failure and provide clinical stabilization. TPE can also remove large molecular weight toxins (aromatic amino acids, ammonia, endotoxins) and other factors, which may be responsible for hepatic coma. The frequency of said TPE is not defined as most evidence is based on case reports and case series. Copper is highly protein bound and the volume of distribution for copper is large. Under normal conditions, 90-95% of serum copper is ceruloplasmin-bound with the remaining 5-10% being nonceruloplasmin-bound. TPE efficiently removes both ceruloplasmin- and albumin-bound copper. FFP used for exchange can be helpful in treating the associated coagulopathy. TPE has been used as a bridge to liver transplantation as well as seen to improve survival with native liver, the optimum protocol for same remains uncertain.

Подробное описание

Study population: Children aged 3 to 18 years with Wilson disease (diagnosed as per Leipzig score \>=4) with fulminant presentation (as defined by New Wilson Index\>= 11 and INR \>= 2.5 ).

Adverse effects: Therapeutic plasma exchange has been shown to be safe and effective in improving native liver survival in Wilson disease patients and is currently standard of care in patients with wilson disease with acute liver failure. However, TPE can be associated with risk of adverse events like infections, fluid overload or circulatory insufficiency, hypersensitivity to blood products.

Stopping rule:

1. Septic Shock 2. Anaphylaxis to blood products 3. HE grade3/4 4. INR \> 5 any time point 5. INR \>3.5 24 hours after 3 HVP Patients fulfilling criteria 3, 4 and 5 would be listed for liver transplantation. In case of 1, 2 appropriate medical management will be done as per department protocol.

Intervention:

Group 1: Daily plasma exchange + SMT (Maximum 3+1 sessions during a period of 7 days) Group 2: Alternate day therapeutic plasma exchange + SMT

Вмешательства

• Биопрепарат Plasma Exchange
  • Plasma exchange (1.5 times plasma exchange) * Blood volume: 80ml/kg * Plasma volume = Blood volume x (1 - Hematocrit/100) * TPE volume = 1.5 x plasma volume * Duration: 4 hours
• Другое Standard Medical Treatment
  Standard Medical Treatment

Первичные конечные точки

• To compare the reduction in NWI (New Wilson Index) between both groups at the end of three sessions of plasma exchange [Срок оценки: 7 days]

Вторичные конечные точки (10)

• Comparison of change in serum and urine copper levels on day 7 after initiation of plasmapheresis as compared to baseline in alternate versus daily plasma exchange group. [Срок оценки: Day 7]
• Comparison of overall and native liver survival at day 90 between the two groups [Срок оценки: 90 days]
• Comparison of change in dialysate copper levels at the end of 3rd session between both groups. [Срок оценки: 1 week]
• Comparison of total number of sessions of plasma exchange between both groups as on day 28. [Срок оценки: Day 28]
• Comparison of AST in U/L, ALT in U/L at end of 3rd plasma exchange compared to baseline. [Срок оценки: 1 week]
• Comparison of corrected reticulocyte count (percentage) at end of 3rd plasma exchange compared to baseline. [Срок оценки: 1 week]
• Comparison of International Normalised Ratio (INR) at end of 3rd plasma exchange compared to baseline. [Срок оценки: 1 week]
• Comparison of bilirubin (mg/dL) at end of 3rd plasma exchange compared to baseline. [Срок оценки: 1 week]
• Comparison of albumin (mg/dL) at end of 3rd plasma exchange compared to baseline. [Срок оценки: 1 week]
• Comparison of serious adverse events as defined by CTCAE criteria in both the groups. [Срок оценки: 90 days]

Критерии участия

Критерии включения

• Wilson disease with New Wilson Index of ≥ 11 and INR ≥ 2.5
• Children aged 3 years to 18 years

Критерии исключения

• Grade 3 or grade 4 hepatic encephalopathy
• Septic shock
• Disseminated intravascular coagulation
• Marked hemodynamic instability requiring a high dose of vasopressors (norepinephrine >0.5 mcg/kg/min)
• Any severe cardio-pulmonary pre-existing disease

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Индия · 1 центр

• Institute of Liver & Biliary Sciences — New Delhi

Идентификаторы

NCT: NCT06698991 · ILBS-ALF-07

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗