Darbepoetin in Patients Candidates for Liver Transplant. (EPO-LT Trial)

Official title

Darbepoetin in Patients Candidates for Liver Transplant: Randomized Clinical Trial Protocol. (EPO-LT Trial)

Overview

This is a national multicenter, randomized clinical trial to evaluate the the efficacy and safety of DP administration in patients on the liver transplant waiting list to reduce intraoperative red blood cell concentrate transfusion.

Detailed description

Patients will be randomized to receive (1:1):

1. Intervention group: Darbepoetin (DP) 1.5 mcg/kg subcutaneously, monthly (The patients will receive medication monthly until the liver transplant is performed or if it has not yet been transplanted, a maximum of 3 doses) 2. Control group: Do not Darbepoetin All patients will be evaluated to rule out vitamin B12 and folic acid deficiencies, and supplementation with 1000 mcg/day and 10 mg/day, respectively, will be provided if necessary. All patients, on the liver transplant list, will receive ferric carboxymaltose 1000 mg IV (every month) according to standard clinical practice Patients will be followed for 3 months after LT

Interventions

• Drug Darbepoetin (DP)
  Darbepoetin (DP) 1.5 mcg/kg subcutaneously, monthly (The patients will receive medication monthly until the liver transplant is performed or if it has not yet been transplanted, a maximum of 3 doses)

Primary outcome measures

• to investigate the efficacy and safety of darbepoetin (DP) administration in patients on the liver transplant (LT) waiting list to reduce intraoperative red blood cell concentrate transfusion. [Time frame: perioperative]

Secondary outcome measures (12)

• Investigate the increase in hemoglobin levels [Time frame: through study completion, an average of 1 year]
• Investigate the difference in the percentage of patients receiving intraoperative and during the first 24h after LT, red blood cell concentrate transfusion between the intervention and control groups [Time frame: baseline Visit , perioperative visit, month 3 postoperative]
• Investigate the difference in the percentage of patients receiving intraoperative massive transfusion between the intervention and control groups. [Time frame: perioperative visit]
• Investigate the difference in the percentage of patients who developed severe postoperative complications between the intervention and control groups. [Time frame: Difference in the 3-month severe postoperative complications]
• Investigate the difference in the overall cost of the transplantation from surgery to three months post-transplant, between the intervention and control groups. [Time frame: three months post-transplant]
• To evaluate the difference in postoperative graft survival , between groups [Time frame: the 3 month, 6, and 12 months, postoperative graft survival after liver transplantation, between groups]
• To investigate the difference in the 3 month, 6, and 12 months, postoperative patient survival after liver transplantation, between groups [Time frame: in the 3 month, 6, and 12 months, postoperative patients survival after liver transplantation]
• Impact of DP treatment on the hemostatic profile of patients with chronic liver disease, comparing the changes in the following coagulation marker beta-TG at basal and 4 weeks after administration [Time frame: at basal visit and month1]
• Impact of DP treatment on the changes in the PF4 profile of patients with chronic liver disease, comparing the changes in the fPF4 coagulation marker at basal and 4 weeks after administration [Time frame: at basal visit and month1]
• Impact of DP treatment on the hemostatic profile of patients with chronic liver disease, comparing the fibrinogen marker at basal and 4 weeks after administration [Time frame: at basal visit and month1]
• Impact of DP treatment on the hemostatic profile of patients with chronic liver disease, comparing the changes in theTM-TGA marker at basal and 4 weeks after administration [Time frame: at basal visit and month1]
• Impact of DP treatment , comparing the changes in the following coagulation CTL marker at basal and 4 weeks after administration [Time frame: at basal visit and month1]

Eligibility criteria

Inclusion criteria

• Age ≥ 18 years old
• Patients on the official liver transplant waiting list
• Hemoglobin (Hb) level ≤ 11.5 g/dL
• 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, post ovulation methods) is not an acceptable method of contraception.

Exclusion criteria

• 1\. Acute/subacute liver failure (see appendix 7) 2. Patients with acute-on-chronic liver failure grade III and/or MELD > 35 3. History of thrombosis, including portal vein thrombosis 4. Significant coronary artery disease (requiring angioplasty and/or coronary stent) 5. Serum ferritin > 800 ng/mL and SAT > 50% 6. Anticoagulant/antiplatelet therapy 7. History of seizures 8. Uncontrolled hypertension (requiring ≥2 antihypertensive drugs) 9. Active infection/sepsis (see appendix 8) 10. Lack of patient consent. 11. Pregnancy or breastfeeding. 12. Patients included in other clinical trials in the month before inclusion. 13. 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Spain · 1 center

• Hospital Clinic de Barcelona — Barcelona

Identifiers

NCT: NCT07169643 · EPO-LT Trial

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗