Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| ALSS (alternating DPMAS and TPE) | Experimental | Participants meeting inclusion criteria will receive artificial liver support system (ALSS) therapy in addition to standard of care. ALSS sessions will be performed for up to 7-10 days or until liver transplantation or recovery of hepatic function, whichever occurs first. ALSS modalities will be alternated according to protocol (DPMAS and TPE alternating between sessions). Outcomes will be assessed through Day 28 after hospital admission (or per protocol). |
|
| Standard care | No Intervention | Participants will receive standard of care for ACLF according to institutional protocol without ALSS (no DPMAS and no TPE as part of ALSS). |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| The artificial liver support system (ALSS) - DPMAS/TPE | Device | Device: Double Plasma Molecular Adsorption System (DPMAS) Procedure/Other: Therapeutic Plasma Exchange (TPE) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Transplant-Free Survival at Day 21 | 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). | 21 days after the first ALSS (DPMAS/TPE) session |
| Measure | Description | Time Frame |
|---|---|---|
| Overall Survival at Day 21 | Proportion of patients who are alive (with or without liver transplantation) at Day 21 after initiation of ALSS therapy. | 21 days after the first ALSS session |
| Overall Survival at Day 90 |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Hepatic Encephalopathy Grade | West Haven grade (0-4) | Baseline (before first ALSS session) Daily for 7 days after ALSS initiation Day 14 Day 21 |
| Change in Plasma Ammonia Concentration | µmol/L |
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Petr Piza, MD, MHA | Contact | +420 602 225 077 | petr.piza@ikem.cz | |
| Eva Kieslichova, ass. prof., MD, PhD | Contact | +420 261 363 350 | evki@ikem.cz |
Not provided
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Institute for Clinical and Experimental Medicine (IKEM) | Recruiting | Prague | 14200 | Czechia |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Proportion of patients who are alive (with or without liver transplantation) at Day 90 after initiation of ALSS therapy.
| 90 days after the first ALSS session |
| Liver Transplantation Rate and Timing | Proportion of patients who undergo liver transplantation after initiation of ALSS therapy and time from ALSS initiation to liver transplantation (days). | Up to 90 days after the first ALSS session |
| 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 |
| Change in International Normalized Ratio (INR) | Unit of Measure: INR units | 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 |
| Change in C-reactive Protein (CRP) Concentration | mg/L | Baseline 24 hours after each ALSS session 72 hours after the final ALSS session Day 7 Day 14 |
| Change in Global Liver Disease Severity (Model for End-Stage Liver Disease [MELD] Score) | 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. | Baseline; Day 3; Day 7; Day 14; Day 21 |
| Change From Baseline in Vasopressor Dose (Norepinephrine Equivalent Dose, NED) | 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). | Baseline; 24 hours after each ALSS session; daily until Day 7 (unit: µg/kg/min (norepinephrine equivalent)) |
| Incidence of Treatment-Emergent Adverse Events Related to ALSS (Combined DPMAS + TPE) | 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. | During each ALSS session; up to 7 days after the final ALSS session |
| Change in Fibrinogen Concentration | Unit of Measure: g/L | 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 |
| Change in Platelet Count | Unit of Measure: ×10⁹/L | 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 |
| Change in Viscoelastic Clotting Time (ROTEM/TEG | Unit of Measure: Seconds | 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 |
| Change in Maximum Clot Firmness (ROTEM/TEG) | Unit of Measure: mm | 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 |
| Change in D-dimer Concentration | Unit of Measure: mg/L FEU | 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 |
| Change in Coagulation Factor VIII Activity | Unit of Measure: % 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 |
| Change in von Willebrand Factor Antigen (vWF:Ag) | Unit of Measure: % | 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 |
| Change in von Willebrand Factor Activity (vWF:RCo or vWF:GPIbM) | Unit of Measure: % | 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 |
| Change in ADAMTS-13 Activity | Unit of Measure: % 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 |
| Change in Protein C Activity | Unit of Measure: % 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 |
| Change in Protein S Activity | Unit of Measure: % 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 |
| Change in Procalcitonin (PCT) Concentration | ng/mL | Baseline 24 hours after each ALSS session 72 hours after the final ALSS session Day 7 Day 14 |
| Change in Interleukin-6 (IL-6) Concentration | pg/mL | Baseline 24 hours after each ALSS session 72 hours after the final ALSS session Day 7 Day 14 |
| Change in Total Serum Bilirubin | µmol/L | Baseline Daily for 7 days Day 14 Day 21 |
| Change in Alanine Aminotransferase (ALT) | U/L | Baseline Daily for 7 days Day 14 Day 21 |
| Change in Aspartate Aminotransferase (AST) | U/L | Baseline Daily for 7 days Day 14 Day 21 |
| Change in MELD Score (Model for End-Stage Liver Disease) | Score on a scale from 6 to 40 Higher scores indicate worse liver disease severity. | Baseline Day 3 Day 7 Day 14 Day 21 |
| Change from baseline in serum creatinine. | µmol/L | Baseline Daily for 7 days Day 14 Day 21 |
| Change in Blood Urea Nitrogen (BUN) | mmol/L | Baseline Daily for 7 days Day 14 Day 21 |
| Change in Urine Output | mL/kg/hour | Baseline Daily for 7 days Day 14 Day 21 |
| New requirement for renal replacement therapy compared with baseline. | Yes/No | Baseline Daily for 7 days Day 14 Day 21 |
| Change from baseline in vasopressor dose expressed as norepinephrine-equivalent rate. | µg/kg/min | Baseline (before first ALSS session) 24 hours after each ALSS session Daily through Day 7 |
| Change from baseline in mean arterial pressure | mmHg | Baseline (before first ALSS session) 24 hours after each ALSS session Daily through Day 7 |
| Change from baseline in the ratio of arterial oxygen partial pressure to inspired oxygen fraction. | Ratio (unitless) | Baseline Day 3 Day 7 Day 14 |
| New requirement for invasive mechanical ventilation compared with baseline | Yes/No | Baseline Day 3 Day 7 Day 14 |
| ICU Length of Stay | ICU length of stay is defined as the number of days from ICU admission (date/time) to ICU discharge (date/time). | From ICU admission to ICU discharge, up to 28 days after ICU admission |
| Duration of Total Hospital Admission (Hospital Length of Stay) | Hospital length of stay is defined as the number of days from hospital admission (date/time) to hospital discharge (date/time). | From hospital admission to hospital discharge, up to 90 days after hospital admission |
| Change From Baseline in Mean Arterial Pressure (MAP) | 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). | Baseline; 24 hours after each ALSS session; daily until Day 7 (unit: mmHg) |
| ID | Term |
|---|---|
| D017114 | Liver Failure, Acute |
| ID | Term |
|---|---|
| D017093 | Liver Failure |
| D048550 | Hepatic Insufficiency |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
Not provided
Not provided