Plasma Exchange Half-dose and Extracorporeal Detoxification for ACLF (Phoenix)
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
調査の概要
詳細な説明
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.
研究の種類
入学 (推定)
段階
- 適用できない
連絡先と場所
研究連絡先
- 名前：Tiago B Loza, Graduated Physician
- 電話番号：00351 913013068
- メール：tiago.loza@ulsne.min-saude.pt
研究場所
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Braganza District
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Bragança、Braganza District、ポルトガル、5301-852
- Unidade Hospitalar de Bragança
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コンタクト：
- Tiago B Loza, Consultant Physician
- 電話番号：00351 913013068
- メール：tiago.loza@ulsne.min-saude.pt
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副調査官：
- Carla Gomes
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副調査官：
- Antonio Grilo Novais
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副調査官：
- Carla Pires
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副調査官：
- Raquel Leitão
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副調査官：
- Tiago Ceriz
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参加基準
適格基準
就学可能な年齢
- 大人
- 高齢者
健康ボランティアの受け入れ
説明
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：支持療法
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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介入なし：Conventional therapy
Conventional therapy to ACLF
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実験的：DPMAS plus Plasma exchange
Patients in this arm will be submitted to: DPMAS: selective adsorption therapy; mainly removes bilirrubin and inflammatory mediators AND Half-dose plasma exchange: nonselective plasma removal and replacement by a donor |
Use of extracorporal technique to support patients with acute on chronic liver failure
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Mortality or need for liver transplantation
時間枠：From enrollment to 28 days after
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28-day mortality and/or need for liver transplantation
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From enrollment to 28 days after
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Total bilirrubin level
時間枠：Daily from date of randomization until ICU discharge or liver trasnplant up to 12 weeks
|
Units: mg/dL
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Daily from date of randomization until ICU discharge or liver trasnplant up to 12 weeks
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INR
時間枠：Daily from date of randomization until ICU discharge or liver trasnplant up to 12 weeks
|
International Normalized Ratio
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Daily from date of randomization until ICU discharge or liver trasnplant up to 12 weeks
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|
SOFA
時間枠：Daily from date of randomization until ICU discharge or liver trasnplant up to 12 weeks.
|
Sequential Organ Failure Assessment Score.
Scale: 0-24.
Higher score means worst outcome.
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Daily from date of randomization until ICU discharge or liver trasnplant up to 12 weeks.
|
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CLIF-C ACLF score
時間枠：Measur at day of randomization, 72h after and 7 days after
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Chronic Liver Failure Consortium Acute-on-Chronic Liver Failure score.
Range 0-100
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Measur at day of randomization, 72h after and 7 days after
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Mortality or liver transplant at day 90
時間枠：90 days after randomization
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Mortality or liver transplant at day 90 after randomization
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90 days after randomization
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Encephalopathy
時間枠：Daily from date of randomization until ICU discharge or liver trasnplant up to 12 weeks
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Grade of encephalopathy according West Haven score.
Grade 0-4.
Higher score means worst outcome.
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Daily from date of randomization until ICU discharge or liver trasnplant up to 12 weeks
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Vasopressor free days
時間枠：Daily from date of randomization until ICU discharge or liver trasnplant up to 12 weeks
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Number of days without need of vasopressor support
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Daily from date of randomization until ICU discharge or liver trasnplant up to 12 weeks
|
|
Invasive mechanical ventilation free days
時間枠：Daily from date of randomization until ICU discharge or liver trasnplant up to 12 weeks
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Number of days without need of invasive mechanical ventilation
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Daily from date of randomization until ICU discharge or liver trasnplant up to 12 weeks
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CRRT free days
時間枠：Daily from date of randomization until ICU discharge or liver trasnplant up to 12 weeks
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Number of days without need of Continuous Renal Replacement Therapy
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Daily from date of randomization until ICU discharge or liver trasnplant up to 12 weeks
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Safety issues - bleeding events
時間枠：Daily from date of randomization until ICU discharge or liver trasnplant up to 12 weeks
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Bleeding events will be recorded and classified as major bleeding, clinically relevant non-major bleeding or minor bleeding according to standard critical care definitions.
Assessment will include overt hemorrhage, intracranial bleeding, gastrointestinal bleeding, procedure-related bleeding, transfusion requirements and decreases in hemoglobin levels.
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Daily from date of randomization until ICU discharge or liver trasnplant up to 12 weeks
|
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Safety issues - Coagulation Abnormalities
時間枠：Daily from date of randomization until ICU discharge or liver trasnplant up to 12 weeks
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Serial coagulation monitoring will include INR, fibrinogen concentration, platelet count and activated clotting parameters when applicable.
Development or worsening of coagulopathy during DPMAS or plasma exchange sessions will be documented.
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Daily from date of randomization until ICU discharge or liver trasnplant up to 12 weeks
|
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Safety issues - Hemodynamic Instability
時間枠：Daily from date of randomization until ICU discharge or liver trasnplant up to 12 weeks
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Episodes of hypotension during or after extracorporeal therapy sessions will be recorded, including increases in vasopressor requirements, reduction in mean arterial pressure, arrhythmias or interruption of treatment due to cardiovascular instability.
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Daily from date of randomization until ICU discharge or liver trasnplant up to 12 weeks
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Safety issues - Circuit-Related Complications
時間枠：Daily from date of randomization until ICU discharge or liver trasnplant up to 12 weeks
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Extracorporeal circuit complications will include filter clotting, premature circuit failure, interruption of therapy, vascular access dysfunction, catheter thrombosis and technical complications related to DPMAS or plasma exchange delivery
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Daily from date of randomization until ICU discharge or liver trasnplant up to 12 weeks
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Safety issues - Metabolic and Electrolyte Disturbance
時間枠：Daily from date of randomization until ICU discharge or liver trasnplant up to 12 weeks
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Metabolic complications including acid-base disturbances, electrolyte abnormalities and clinically significant metabolic derangements occurring during therapy will be recorded
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Daily from date of randomization until ICU discharge or liver trasnplant up to 12 weeks
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Safety issues - Hematologic Complications
時間枠：Daily from date of randomization until ICU discharge or liver trasnplant up to 12 weeks
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Development of thrombocytopenia, hemolysis or significant transfusion requirements associated with extracorporeal therapy will be assessed throughout treatment and follow-up.
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Daily from date of randomization until ICU discharge or liver trasnplant up to 12 weeks
|
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Safety issues - Infectious Complications
時間枠：Daily from date of randomization until ICU discharge or liver trasnplant up to 12 weeks
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New infections, catheter-related bloodstream infections, bacteremia and sepsis episodes occurring during treatment or ICU stay will be documented.
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Daily from date of randomization until ICU discharge or liver trasnplant up to 12 weeks
|
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Safety issues - Renal Complications
時間枠：Daily from date of randomization until ICU discharge or liver trasnplant up to 12 weeks
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Renal outcomes will include development or worsening of acute kidney injury, need for renal replacement therapy and renal replacement therapy-free days.
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Daily from date of randomization until ICU discharge or liver trasnplant up to 12 weeks
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Safety issues - Neurological Complications
時間枠：Daily from date of randomization until ICU discharge or liver trasnplant up to 12 weeks
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Neurological adverse events including worsening hepatic encephalopathy, seizures, cerebral edema or unexplained neurological deterioration will be monitored and documented.
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Daily from date of randomization until ICU discharge or liver trasnplant up to 12 weeks
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協力者と研究者
出版物と役立つリンク
一般刊行物
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
研究記録日
主要日程の研究
研究開始 (推定)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- Phoenix
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
IPD プランの説明
IPD 共有時間枠
IPD 共有アクセス基準
IPD 共有サポート情報タイプ
- STUDY_PROTOCOL
- SAP
- ICF
- CSR
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
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