Acute Liver Failure
Conditions
Keywords
acute liver failure
Brief summary
The artificial liver support system (ALSS) in patients with acute on chronic liver failure - the use of combined molecular adsorption system with double plasma (DPMAS) and therapeutic plasma exchange (TPE), its effect on primary coagulation, inflammation and the function of vital organs.
Detailed description
In patients with ACLF we assume the use of the proposed protocol of combined support therapy (consisting of a hemoadsorption system - DPMAS (double plasma molecular absorption system) and therapeutic plasma (TPE), with the basic aim of improving clinical condition (organ dysfunction) to allow the regeneration of liver parenchyma or to perform liver transplantation.
Interventions
DEVICEThe artificial liver support system (ALSS) - DPMAS/TPE
Device: Double Plasma Molecular Adsorption System (DPMAS) Procedure/Other: Therapeutic Plasma Exchange (TPE)
Sponsors
Institute for Clinical and Experimental Medicine
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Adult patient, age ≥18 years * Expressed consent to the inclusion * Patient hospitalized on ICU with ALF or ACLF diagnosis * Recently meeting the inclusion to liver transplantation * Present on a waiting list to liver transplant * Unsuitable for inclusion to liver transplantation - indicated for support therapy only, but not indented to palliative care
Exclusion criteria
* Disagreement with the study * Infaust prognosis with expected survival less than 24 hours * Physiologically/biologically very advanced stage patients condition, severe lung disease (Gold criteria 3 or 4), heart failure (functional class NYHA III or IV) or neurological disease, as well as ACLF-3. * Advanced oncological disease (expected life expectancy below 6 months) * Severe degree of Frailty syndrome in secondary severe sarcopenia (muscle and malnutrition) or reduced performance state according
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Transplant-Free Survival at Day 21 | 21 days after the first ALSS (DPMAS/TPE) session | Proportion of patients with acute liver failure who are alive without liver transplantation at Day 21 after initiation of artificial liver support therapy (combined DPMAS + TPE). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival at Day 21 | 21 days after the first ALSS session | Proportion of patients who are alive (with or without liver transplantation) at Day 21 after initiation of ALSS therapy. |
| Overall Survival at Day 90 | 90 days after the first ALSS session | Proportion of patients who are alive (with or without liver transplantation) at Day 90 after initiation of ALSS therapy. |
| Liver Transplantation Rate and Timing | Up to 90 days after the first ALSS session | Proportion of patients who undergo liver transplantation after initiation of ALSS therapy and time from ALSS initiation to liver transplantation (days). |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in Global Liver Disease Severity (Model for End-Stage Liver Disease [MELD] Score) | Baseline; Day 3; Day 7; Day 14; Day 21 | Change from baseline in the Model for End-Stage Liver Disease (MELD) score, a validated severity scale of chronic liver disease. The MELD score is calculated from serum bilirubin, serum creatinine, and INR (International Normalized Ratio). Score range: 6 to 40, with higher scores indicating more severe liver disease and worse prognosis. Change from baseline will be calculated at each time point as: (MELD at time point - MELD at baseline). MELD will be calculated using the standard formula. |
| Change From Baseline in Vasopressor Dose (Norepinephrine Equivalent Dose, NED) | Baseline; 24 hours after each ALSS session; daily until Day 7 (unit: µg/kg/min (norepinephrine equivalent)) | Norepinephrine equivalent dose (NED) will be recorded at baseline, 24 hours after each ALSS session, and then daily through Day 7. Change from baseline will be calculated at each time point as: (NED at time point - NED at baseline). |
| Incidence of Treatment-Emergent Adverse Events Related to ALSS (Combined DPMAS + TPE) | During each ALSS session; up to 7 days after the final ALSS session | Number of participants with treatment-emergent adverse events (TEAEs) considered related to ALSS (combined DPMAS + TPE) occurring during each ALSS session or within 7 days after the final ALSS session, including: procedure-related bleeding, hemodynamic instability during the procedure, allergic or anaphylactic reactions, circuit clotting, and clinically significant electrolyte disturbances requiring intervention. Relationship to ALSS will be assessed by the investigator according to predefined criteria. |
| Change in Fibrinogen Concentration | Baseline: Within 1 hour before first DPMAS + TPE session Immediate Post-Procedure: Within 1 hour after each ALSS session Early Post-Intervention: 24 hours after the final ALSS session Follow-Up: Day 3 and Day 7 | Unit of Measure: g/L |
| Change in Platelet Count | Baseline: Within 1 hour before first DPMAS + TPE session Post-Procedure: Within 12 hour after each ALSS session Early Post-Intervention: 24 hours after the final ALSS session Follow-Up: Day 3 and Day 7 | Unit of Measure: ×10⁹/L |
| Change in Viscoelastic Clotting Time (ROTEM/TEG | Baseline: Within 1 hour before first DPMAS + TPE session Post-Procedure: Within 2 hour after each ALSS session Early Post-Intervention: 24 hours after the final ALSS session Follow-Up: Day 3 and Day 7 | Unit of Measure: Seconds |
| Change in Maximum Clot Firmness (ROTEM/TEG) | Baseline: Within 1 hour before first DPMAS + TPE session Post-Procedure: Within 2 hour after each ALSS session Early Post-Intervention: 24 hours after the final ALSS session Follow-Up: Day 3 and Day 7 | Unit of Measure: mm |
| Change in D-dimer Concentration | Baseline: Within 1 hour before first DPMAS + TPE session Immediate Post-Procedure: Within 12 hour after each ALSS session Early Post-Intervention: 24 hours after the final ALSS session Follow-Up: Day 3 and Day 7 | Unit of Measure: mg/L FEU |
| Change in Coagulation Factor VIII Activity | Baseline: Within 1 hour before first DPMAS + TPE session Immediate Post-Procedure: Within 1 hour after each ALSS session Early Post-Intervention: 24 hours after the final ALSS session Follow-Up: Day 3 and Day 7 | Unit of Measure: % activity |
| Change in von Willebrand Factor Antigen (vWF:Ag) | Baseline: Within 1 hour before first DPMAS + TPE session Immediate Post-Procedure: Within 1 hour after each ALSS session Early Post-Intervention: 24 hours after the final ALSS session Follow-Up: Day 3 and Day 7 | Unit of Measure: % |
| Change in von Willebrand Factor Activity (vWF:RCo or vWF:GPIbM) | Baseline: Within 1 hour before first DPMAS + TPE session Immediate Post-Procedure: Within 1 hour after each ALSS session Early Post-Intervention: 24 hours after the final ALSS session Follow-Up: Day 3 and Day 7 | Unit of Measure: % |
| Change in ADAMTS-13 Activity | Baseline: Within 1 hour before first DPMAS + TPE session Immediate Post-Procedure: Within 1 hour after each ALSS session Early Post-Intervention: 24 hours after the final ALSS session Follow-Up: Day 3 and Day 7 | Unit of Measure: % activity |
| Change in Protein C Activity | Baseline: Within 1 hour before first DPMAS + TPE session Immediate Post-Procedure: Within 1 hour after each ALSS session Early Post-Intervention: 24 hours after the final ALSS session Follow-Up: Day 3 and Day 7 | Unit of Measure: % activity |
| Change in Protein S Activity | Baseline: Within 1 hour before first DPMAS + TPE session Immediate Post-Procedure: Within 1 hour after each ALSS session Early Post-Intervention: 24 hours after the final ALSS session Follow-Up: Day 3 and Day 7 | Unit of Measure: % activity |
| Change in Procalcitonin (PCT) Concentration | Baseline 24 hours after each ALSS session 72 hours after the final ALSS session Day 7 Day 14 | ng/mL |
| Change in Hepatic Encephalopathy Grade | Baseline (before first ALSS session) Daily for 7 days after ALSS initiation Day 14 Day 21 | West Haven grade (0-4) |
| Change in Total Serum Bilirubin | Baseline Daily for 7 days Day 14 Day 21 | µmol/L |
| Change in Alanine Aminotransferase (ALT) | Baseline Daily for 7 days Day 14 Day 21 | U/L |
| Change in Aspartate Aminotransferase (AST) | Baseline Daily for 7 days Day 14 Day 21 | U/L |
| Change in MELD Score (Model for End-Stage Liver Disease) | Baseline Day 3 Day 7 Day 14 Day 21 | Score on a scale from 6 to 40 Higher scores indicate worse liver disease severity. |
| Change from baseline in serum creatinine. | Baseline Daily for 7 days Day 14 Day 21 | µmol/L |
| Change in Blood Urea Nitrogen (BUN) | Baseline Daily for 7 days Day 14 Day 21 | mmol/L |
| Change in Urine Output | Baseline Daily for 7 days Day 14 Day 21 | mL/kg/hour |
| New requirement for renal replacement therapy compared with baseline. | Baseline Daily for 7 days Day 14 Day 21 | Yes/No |
| Change from baseline in vasopressor dose expressed as norepinephrine-equivalent rate. | Baseline (before first ALSS session) 24 hours after each ALSS session Daily through Day 7 | µg/kg/min |
| Change from baseline in mean arterial pressure | Baseline (before first ALSS session) 24 hours after each ALSS session Daily through Day 7 | mmHg |
| Change from baseline in the ratio of arterial oxygen partial pressure to inspired oxygen fraction. | Baseline Day 3 Day 7 Day 14 | Ratio (unitless) |
| New requirement for invasive mechanical ventilation compared with baseline | Baseline Day 3 Day 7 Day 14 | Yes/No |
| ICU Length of Stay | From ICU admission to ICU discharge, up to 28 days after ICU admission | ICU length of stay is defined as the number of days from ICU admission (date/time) to ICU discharge (date/time). |
| Duration of Total Hospital Admission (Hospital Length of Stay) | From hospital admission to hospital discharge, up to 90 days after hospital admission | Hospital length of stay is defined as the number of days from hospital admission (date/time) to hospital discharge (date/time). |
| Change From Baseline in Mean Arterial Pressure (MAP) | Baseline; 24 hours after each ALSS session; daily until Day 7 (unit: mmHg) | Mean arterial pressure (MAP) will be recorded at baseline, 24 hours after each ALSS session, and then daily through Day 7. Change from baseline will be calculated at each time point as: (MAP at time point - MAP at baseline). |
| Change in Interleukin-6 (IL-6) Concentration | Baseline 24 hours after each ALSS session 72 hours after the final ALSS session Day 7 Day 14 | pg/mL |
| Change in Plasma Ammonia Concentration | Baseline (within 6 hours before first ALSS session) Immediately after each ALSS session 24 hours after the final ALSS session Day 3, Day 7, Day 14, Day 21 | µmol/L |
| Change in International Normalized Ratio (INR) | Baseline: Within 1 hour before the first DPMAS + TPE session Immediate Post-Procedure: Within 1 hour after each ALSS session Early Post-Intervention: 24 hours after the final ALSS session Follow-Up: Day 3 and Day 7 | Unit of Measure: INR units |
| Change in C-reactive Protein (CRP) Concentration | Baseline 24 hours after each ALSS session 72 hours after the final ALSS session Day 7 Day 14 | mg/L |
Countries
Czechia
Contacts
Primary ContactPetr Piza, MD, MHA
Backup ContactEva Kieslichova, ass. prof., MD, PhD
Outcome results
None listed