DARBEPOETIN ALFA for Candidates for liver transplantation|Chronic liver disease|Anemia

Inclusion criteria

• {"criterion_text":"- Age ≥ 18 years old\n- Patients on the oficial liver transplant waiting list\n- Hemoglobin (Hb) level ≤ 11.5 g/dL\n- Women of child-bearing potential* must have a negative pregnancy test in serum before the inclusion in the study and agree to use highly effective contraceptive methods during the study. Highly effective contraceptive methods will include: intrauterine device, bilateral tubal occlusion, vasectomized partner and sexual abstinence** (only if refraining from heterosexual intercourse during the period of twelve months).Hormonal contraceptive methods will be avoided due to the risk of adverse events and impairment of liver function. * A woman will be considered of childbearing potential, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as 0 menses for 12 months without an alternative medical cause. A high follicle stimulating hormone level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single follicle stimulating hormone measurement is insufficient. ** Sexual abstinence should only be used as a contraceptive method if it is in line with the subjects’ usual and preferred lifestyle. Periodic abstinence (calendar, symptothermal, postovulation methods) is not an acceptable method of contraception."}

Exclusion criteria

• {"criterion_text":"- Acute/subacute liver failure (see appendix 7)\n- Lack of patient consent\n- Pregnancy or breastfeeding.\n- Patients included in other clinical trials in the month before inclusion.\n- Patients with mental incapacity, language barrier, bad social support or any other reason considered by the investigator precluding adequate understanding, cooperation or compliance in the study.\n- Patients with acute-on-chronic liver failure grade III and/or MELD > 35\n- History of thrombosis, including portal vein thrombosis\n- Significant coronary artery disease (requiring angioplasty and/or coronary stent)\n- Serum ferritin > 800 ng/mL and SAT > 50%\n- Anticoagulant/antiplatelet therapy\n- History of seizures\n- Uncontrolled hypertension (requiring ≥2 antihypertensive drugs)\n- Active infection/sepsis (see appendix 8)"}

Primary endpoints

• {"endpoint_text":"- Difference in the percentage of patients receiving intraoperative (LT) red blood cell transfusions between the intervention group and the control group.","definition_or_measurement_approach":"Comparison of the percentage (proportion) of patients receiving intraoperative red blood cell transfusions between intervention and control groups."}

Secondary endpoints

• {"endpoint_text":"- Absolute differences from baseline in hemoglobin levels basal and at 4, 8, 12 or 16 weeks after the administration of DP, or at the time of liver transplantation, between the intervention group and the control group.","definition_or_measurement_approach":"Absolute change from baseline in hemoglobin measured at baseline and at 4, 8, 12 or 16 weeks after DP administration or at time of transplantation, compared between groups."}
• {"endpoint_text":"- Difference in the percentage of patients receiving intraoperative and during the first 24h after LT, red blood cell transfusions between the intervention group and the control group.","definition_or_measurement_approach":"Comparison of the percentage of patients receiving RBC transfusions intraoperatively and during the first 24 hours after LT between groups."}
• {"endpoint_text":"- Difference in the percentage of patients receiving massive transfusions (>6 units of red blood cells) intraoperatively, between the intervention and control groups.","definition_or_measurement_approach":"Comparison of proportion of patients receiving massive transfusion (>6 units RBC) intraoperatively between groups."}
• {"endpoint_text":"- Difference in the 3-month severe postoperative complications assessed by the Comprehensive Charlson Index, between groups.","definition_or_measurement_approach":"Comparison of severe postoperative complications at 3 months assessed by the Comprehensive Charlson Index between groups."}
• {"endpoint_text":"- Difference in the overall cost (direct and indirect) of the transplantation, conducting a cost-effective analysis from surgery to three months post-transplant, between groups.","definition_or_measurement_approach":"Cost-effectiveness analysis comparing overall direct and indirect transplantation costs from surgery to three months post-transplant between groups."}
• {"endpoint_text":"- To evaluate the difference in the 3 month, 6, and 12 months, postoperative graft survival after liver transplantation, between groups","definition_or_measurement_approach":"Comparison of graft survival at 3, 6 and 12 months post-transplant between groups."}
• {"endpoint_text":"- To evaluate the difference in the 3 month, 6, and 12 months, postoperative patients’ survival after liver transplantation, between groups","definition_or_measurement_approach":"Comparison of patient survival at 3, 6 and 12 months post-transplant between groups."}
• {"endpoint_text":"- Impact of DP treatment on the hemostatic profile of patients with chronic liver disease, comparing the changes in the following coagulation and fibrinolysis markers at basal and 4 weeks after administration: beta TG, PF4, VWF, fibrinogen, TM-TGA, CLT, D dimer, TAT, PAP, hepcidin, erythropoietin, between groups (see Table 1)","definition_or_measurement_approach":"Comparison of changes from baseline to 4 weeks in specified coagulation and fibrinolysis biomarkers (beta TG, PF4, VWF, fibrinogen, TM-TGA, CLT, D dimer, TAT, PAP, hepcidin, erythropoietin) between groups."}
• {"endpoint_text":"- To explore the impact of anemia on complications of portal hypertension, evaluated by the number and type of acute decompensations (acute gastrointestinal bleeding, infection, encephalopathy, ascites/edemas, renal disfunction) occurred in both groups.","definition_or_measurement_approach":"Comparison of number and type of acute decompensations related to portal hypertension between groups."}
• {"endpoint_text":"- To explore the impact of the anemia on the quality of life measured by the EuroQol-5D scale during all visits, in both groups.","definition_or_measurement_approach":"Comparison of EQ-5D quality-of-life scores across study visits between groups."}
• {"endpoint_text":"- To explore the predictors of poor response to DP treatment defined as the increase in the hemoglobin level < 1 g/dL after 1 month of treatment.","definition_or_measurement_approach":"Analysis of predictors of poor response defined as Hb increase <1 g/dL after 1 month of treatment."}
• {"endpoint_text":"- Proportion of patients and severity of treatment-related adverse events during the study period,","definition_or_measurement_approach":"Assessment of proportion and severity of treatment-related adverse events during the study period."}

Spain

Earliest CTIS Part Ii Submission Date

11-07-2025

Latest Decision Or Authorization Date

13-08-2025

Processing Time Days

33

Number Of Sites

5

Number Of Participants

140

Primary sponsor

Full Name

Fundacio De Recerca Clinic Barcelona-Institut D’Investigacions Biomediques August Pi I Sunyer

Organisation Type

Laboratory/Research/Testing facility

Country Of Registered Address

Spain