Plasma Exchange Half-dose and Extracorporeal Detoxification for ACLF

N/ANot Yet RecruitingNCT07593638

Unidade Local de Saude do Nordeste240 enrolled

Overview

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

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.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Mortality or need for liver transplantation

28-day mortality and/or need for liver transplantation

Time frame: From enrollment to 28 days after

Secondary Outcomes

Total bilirrubin level

Units: mg/dL

Time frame: Daily from date of randomization until ICU discharge or liver trasnplant up to 12 weeks

INR

International Normalized Ratio

Time frame: Daily from date of randomization until ICU discharge or liver trasnplant up to 12 weeks

SOFA

Sequential Organ Failure Assessment Score. Scale: 0-24. Higher score means worst outcome.

Time frame: Daily from date of randomization until ICU discharge or liver trasnplant up to 12 weeks.

CLIF-C ACLF score

Chronic Liver Failure Consortium Acute-on-Chronic Liver Failure score. Range 0-100

Time frame: Measur at day of randomization, 72h after and 7 days after

Mortality or liver transplant at day 90

Mortality or liver transplant at day 90 after randomization

Time frame: 90 days after randomization

Encephalopathy

Grade of encephalopathy according West Haven score. Grade 0-4. Higher score means worst outcome.

Time frame: Daily from date of randomization until ICU discharge or liver trasnplant up to 12 weeks

Vasopressor free days

Number of days without need of vasopressor support

Time frame: Daily from date of randomization until ICU discharge or liver trasnplant up to 12 weeks

Invasive mechanical ventilation free days

Number of days without need of invasive mechanical ventilation

Time frame: Daily from date of randomization until ICU discharge or liver trasnplant up to 12 weeks

CRRT free days

Number of days without need of Continuous Renal Replacement Therapy

Time frame: Daily from date of randomization until ICU discharge or liver trasnplant up to 12 weeks

Safety issues - bleeding events

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.

Time frame: Daily from date of randomization until ICU discharge or liver trasnplant up to 12 weeks

Safety issues - Coagulation Abnormalities

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.

Time frame: Daily from date of randomization until ICU discharge or liver trasnplant up to 12 weeks

Safety issues - Hemodynamic Instability

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.

Time frame: Daily from date of randomization until ICU discharge or liver trasnplant up to 12 weeks

Safety issues - Circuit-Related Complications

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

Time frame: Daily from date of randomization until ICU discharge or liver trasnplant up to 12 weeks

Safety issues - Metabolic and Electrolyte Disturbance

Metabolic complications including acid-base disturbances, electrolyte abnormalities and clinically significant metabolic derangements occurring during therapy will be recorded

Time frame: Daily from date of randomization until ICU discharge or liver trasnplant up to 12 weeks

Safety issues - Hematologic Complications

Development of thrombocytopenia, hemolysis or significant transfusion requirements associated with extracorporeal therapy will be assessed throughout treatment and follow-up.

Time frame: Daily from date of randomization until ICU discharge or liver trasnplant up to 12 weeks

Safety issues - Infectious Complications

New infections, catheter-related bloodstream infections, bacteremia and sepsis episodes occurring during treatment or ICU stay will be documented.

Time frame: Daily from date of randomization until ICU discharge or liver trasnplant up to 12 weeks

Safety issues - Renal Complications

Renal outcomes will include development or worsening of acute kidney injury, need for renal replacement therapy and renal replacement therapy-free days.

Time frame: Daily from date of randomization until ICU discharge or liver trasnplant up to 12 weeks

Safety issues - Neurological Complications

Neurological adverse events including worsening hepatic encephalopathy, seizures, cerebral edema or unexplained neurological deterioration will be monitored and documented.

Time frame: Daily from date of randomization until ICU discharge or liver trasnplant up to 12 weeks

Plasma Exchange Half-dose and Extracorporeal Detoxification for ACLF

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts