Darbepoetin in patients candidates for liver transplant: randomized clinical trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

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

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

25 Nov 2025 → ongoing

Decision date (initial)

2025-08-13

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

CONVOCATORIA PROYECTOS DE I+D+I EN SALUD (Proyecto de Inv) Expediente Nº PI24/00519

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Prophylaxis

The main objective of this proposal is 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.

Secondary objectives 12

1. Investigate the increase in hemoglobin levels at 4, 8, 12, and 16 weeks after the administration of DP, or at the time of liver transplantation, between the intervention group and the control group.
2. 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.
3. Investigate the difference in the percentage of patients receiving intraoperative massive transfusion between the intervention and control groups.
4. Investigate the difference in the percentage of patients who developed severe postoperative complications between the intervention and control groups.
5. Investigate the difference in the overall cost of the transplantation from surgery to three months post-transplant, between the intervention and control groups.
6. To evaluate the difference in the 3 month, 6, and 12 months, postoperative graft survival after liver transplantation, between groups.
7. To investigate the difference in the 3 month, 6, and 12 months, postoperative patient survival after liver transplantation, between groups
8. To explore the impact of DP treatment on the hemostatic profile of patients with chronic liver disease.
9. To explore the impact of anemia on complications of portal hypertension.
10. To explore the impact of the anemia in the quality of life.
11. To explore the predictors of poor response to DP treatment.
12. To explore the security in both groups

Conditions and MedDRA coding

hepatic trasplant

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Age ≥ 18 years old
2. Patients on the oficial liver transplant waiting list
3. Hemoglobin (Hb) level ≤ 11.5 g/dL
4. 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 13

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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Difference in the percentage of patients receiving intraoperative (LT) red blood cell transfusions between the intervention group and the control group.

Secondary endpoints 12

1. 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.
2. 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.
3. Difference in the percentage of patients receiving massive transfusions (>6 units of red blood cells) intraoperatively, between the intervention and control groups.
4. Difference in the 3-month severe postoperative complications assessed by the Comprehensive Charlson Index, between groups.
5. 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.
6. To evaluate the difference in the 3 month, 6, and 12 months, postoperative graft survival after liver transplantation, between groups
7. To evaluate the difference in the 3 month, 6, and 12 months, postoperative patients’ survival after liver transplantation, between groups
8. 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)
9. 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.
10. To explore the impact of the anemia on the quality of life measured by the EuroQol-5D scale during all visits, in both groups.
11. 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.
12. Proportion of patients and severity of treatment-related adverse events during the study period,

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

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

Sponsor organisation

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

Address

Calle Rosellon 149-153

City

Barcelona

Postcode

08036

Country

Spain

Scientific contact point

Organisation

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

Contact name

Annabel Blasi

Public contact point

Organisation

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

Contact name

Annabel Blasi

Locations

1 EU/EEA country · 5 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 8 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications