Plasma Exchange Half-dose and Extracorporeal Detoxification for ACLF

Обзор

Clinical trial The goal of this clinical trial is to learn if a liver support protocol works to treat Liver failure in adults. The main questions it aims to answer are: * Does hemoadsorption plus half-dose plasma exchange provide support to liver failure patients until recovery or transplant * What medical problems do participants have during the technique? Researchers will compare DPMAS plus half-dose plasma exchange with conventional treatment to evaluate a gain in recovery Participants will: * Be submitted to DPMAS plus half dose plasma exchange daily according to protocol. * Monitoring will be continuous in the ICU

Подробное описание

Acute-on-chronic liver failure (ACLF) is a complex and life-threatening syndrome that develops when chronic liver disease suddenly decompensates. It is marked by systemic inflammation, the accumulation of albumin-bound toxins, and the rapid onset of multiorgan failure. The main drivers of this process include elevated levels of bilirubin and bile acids, an intense cytokine storm, and a profound loss of the liver's synthetic capacity.

Clinicians classify ACLF into three grades of increasing severity, with 28-day mortality ranging from 20-30% in grade 1, 40-60% in grade 2, and exceeding 70% in grade 3. Despite important advances in understanding its pathophysiology, effective therapeutic options remain limited, particularly for patients who are not candidates for liver transplantation. At present, no widely accepted extracorporeal liver support therapy has proven consistently successful. The central goal of care is therefore to stabilize the patient, control the inflammatory response and toxin burden, and create the conditions for hepatic regeneration or to serve as a bridge to transplantation.

Over the past decades, extracorporeal blood purification techniques have been explored as adjunctive therapies. High-volume plasma exchange has shown potential to reduce inflammatory mediators and improve survival in selected patients with acute liver failure or ACLF. However, its routine use is constrained by high plasma consumption, significant transfusion-related risks, and logistical challenges.

The Double Plasma Molecular Adsorption System (DPMAS), which employs the BS330 adsorber for bilirubin and bile acids and the HA330-2 adsorber for cytokines and inflammatory mediators, offers a more targeted approach. When combined with half-dose plasma exchange and appropriate replacement of plasma components, this hybrid detoxification strategy achieves effective toxin removal and immune modulation while substantially reducing the volume of plasma required. In our intensive care unit, this hybrid protocol has been developed and refined through clinical experience and informed by earlier studies. Several critically ill patients with ACLF who would otherwise have died or required urgent transplantation showed encouraging signs of recovery. Nevertheless, robust evidence from a randomized controlled trial is still needed to confirm the efficacy and safety of this combined approach in patients with ACLF of reversible aetiology.

Вмешательства

• Устройство DPMAS plus plasma exchange
  Use of extracorporal technique to support patients with acute on chronic liver failure

Первичные конечные точки

• Mortality or need for liver transplantation [Срок оценки: From enrollment to 28 days after]

Вторичные конечные точки (12)

• Total bilirrubin level [Срок оценки: Daily from date of randomization until ICU discharge or liver trasnplant up to 12 weeks]
• INR [Срок оценки: Daily from date of randomization until ICU discharge or liver trasnplant up to 12 weeks]
• SOFA [Срок оценки: Daily from date of randomization until ICU discharge or liver trasnplant up to 12 weeks.]
• CLIF-C ACLF score [Срок оценки: Measur at day of randomization, 72h after and 7 days after]
• Mortality or liver transplant at day 90 [Срок оценки: 90 days after randomization]
• Encephalopathy [Срок оценки: Daily from date of randomization until ICU discharge or liver trasnplant up to 12 weeks]
• Vasopressor free days [Срок оценки: Daily from date of randomization until ICU discharge or liver trasnplant up to 12 weeks]
• Invasive mechanical ventilation free days [Срок оценки: Daily from date of randomization until ICU discharge or liver trasnplant up to 12 weeks]
• CRRT free days [Срок оценки: Daily from date of randomization until ICU discharge or liver trasnplant up to 12 weeks]
• Safety issues - bleeding events [Срок оценки: Daily from date of randomization until ICU discharge or liver trasnplant up to 12 weeks]
• Safety issues - Coagulation Abnormalities [Срок оценки: Daily from date of randomization until ICU discharge or liver trasnplant up to 12 weeks]
• Safety issues - Hemodynamic Instability [Срок оценки: Daily from date of randomization until ICU discharge or liver trasnplant up to 12 weeks]

Критерии участия

Критерии включения

• Written informed consent for participation in the study
• Admission to the ICU with a diagnosis of ACLF of reversible etiology (infection, bleeding, alcohol-related, toxic, etc.)
• Total bilirubin ≥ 12 mg/dL and INR ≥ 1.5
• On the waiting list for liver transplantation or not a candidate for transplantation but with an indication for supportive therapy

Критерии исключения

• Refusal to provide consent
• Pregnancy
• Expected survival < 24 hours due to disease severity (hemodynamic instability requiring norepinephrine > 0.20 mcg/kg/min and/or mechanical ventilation with PaO₂/FiO₂ < 150 and/or non-hepatic coma)
• ACLF severity greater than CLIF-C ACLF grade 3
• Advanced organ dysfunction: Pulmonary (GOLD stage 3 or 4) and/or Cardiac (NYHA functional class III or IV)
• Advanced or metastatic oncological disease (life expectancy < 6 months)
• Marked frailty syndrome or secondary sarcopenia
• Participation in another clinical trial within the previous 3 months

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

Поддерживающая терапия

Центры проведения

Португалия · 1 центр

• Unidade Hospitalar de Bragança — Bragança

Публикации

• Schonfelder K, Hirsch LK, Kribben A, Jahn M, Tyczynski B, Friebus-Kardash J. Artificial liver support with Cytosorb and continuous veno-venous hemodiafiltration versus advanced organ support (ADVOS) for critically ill patients with hyperbilirubinemia and acute-on-chronic liver failure (ACLF). BMC Nephrol. 2025 Aug 4;26(1):432. doi: 10.1186/s12882-025-04342-6. PMID 40759919
• Toapanta-Gaibor D, Sanchez-Ballesteros J, Gonzalez-Fernandez M, Broch-Porcar MJ. Advances in extracorporeal liver support for acute and acute-on-chronic liver failure. Med Intensiva (Engl Ed). 2025 Nov;49(11):502291. doi: 10.1016/j.medine.2025.502291. Epub 2025 Aug 11. PMID 40796412
• Karkmann K, Piecha F, Runzi AC, Schulz L, von Wulffen M, Benten D, Kluwe J, Wege H. [Management of compensated liver cirrhosis 2018 - Evidence based prophylactic measures]. Z Gastroenterol. 2018 Jan;56(1):55-69. doi: 10.1055/s-0043-124000. Epub 2018 Jan 9. German. PMID 29316579
• Scharf C, Liebchen U, Paal M, Becker-Pennrich A, Irlbeck M, Zoller M, Schroeder I. Successful elimination of bilirubin in critically ill patients with acute liver dysfunction using a cytokine adsorber and albumin dialysis: a pilot study. Sci Rep. 2021 May 13;11(1):10190. doi: 10.1038/s41598-021-89712-4. PMID 33986443
• Double Plasma Molecular Adsorption System as Treatment in A Severe Acute-On-Chronic Liver Failure in A Patient with Autoimmune Hepatitis Author: Mariana Zavala-Gómez, Rodrigo López-Contreras, Daniel Alvarez-Lara, Carlos Cortez-Hernadez, Llia Rizo-Topete https://dx.doi.org/10.47746/FMCR.2025.6104
• Xu W, Zhu S, Yang L, Li Z, Wu L, Zhang Y, Chen J, Deng Z, Luo Q, Peng L. Safety and efficacy of double plasma molecular adsorption system with sequential low-volume plasma exchange in intermediate-stage hepatitis B virus-related acute-on-chronic liver failure. J Med Virol. 2023 Mar;95(3):e28650. doi: 10.1002/jmv.28650. PMID 36897008
• Marcello M, Ronco C. Bilirubin Adsorption with DPMAS: Mechanism of Action and Efficacy of Anion Exchange Resin. Contrib Nephrol. 2023;200:201-209. doi: 10.1159/000526729. Epub 2023 Jun 1. PMID 37263196

Идентификаторы

NCT: NCT07593638 · Phoenix

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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