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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.
Patients will be randomized to receive (1:1):
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Darbepoetin arm | Experimental | Darbepoetin (DP) 1.5 mcg/kgsub cutaneously, 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) |
|
| No intervention arm | No Intervention | No administration darbepoetin(DP). |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Darbepoetin (DP) | Drug | 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) |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Difference in the percentage of patients receiving intraoperative (LT) red blood cell transfusions between the intervention group and the control group. | perioperative |
| Measure | Description | Time Frame |
|---|---|---|
| Investigate the increase in hemoglobin levels | 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 | through study completion, an average of 1 year |
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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.
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Anna cruceta, Dr | Contact | +93 2275400 | acruceta@recerca.clinic.cat |
| Name | Affiliation | Role |
|---|---|---|
| Annabel Blasi, Dr | Fundació de Recerca ClÃnic Barcelona - Institut D'Investigacions Biomèdiques Agustà Pà i Sunyer | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hospital Clinic de Barcelona | Recruiting | Barcelona | Catalonia | 08036 | Spain |
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| ID | Term |
|---|---|
| D000068256 | Darbepoetin alfa |
| ID | Term |
|---|---|
| D004921 | Erythropoietin |
| D003115 | Colony-Stimulating Factors |
| D006023 | Glycoproteins |
| D006001 | Glycoconjugates |
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This is a phase III, 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
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| 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 |
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 |
| 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. | Difference in the percentage of patients receiving massive transfusions(>6 units of red blood cells) | perioperative visit |
| Investigate the difference in the percentage of patients who developed severe postoperative complications between the intervention and control groups. | assessed by the Comprehensive Charlson Index, between groups | 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. | Difference in the overall cost (direct and indirect) of the transplantation, conducting a cost-effective analysis between groups | three months post-transplant |
| To evaluate the difference in postoperative graft survival , between groups | To evaluate the difference in the 3 month, 6, and 12 months, postoperative graft survival after liver transplantation, between groups | 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 | To evaluate the difference in the 3 month, 6, and 12 months, postoperative patients' survival after liver transplantation, between groups | 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 | changes in the beta-TG marker (mg/mL) | 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 | changes in the e PF4 (heprin antibody test ) in (IU/dL) | 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 | changes in the fibrinogen (g/L) | 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 | changes in the TM-TGA(ng/mL) | 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 | changes in the CLT, (clothing and lysis time test ) (minutes) between groups | at basal visit and month1 |
| Impact of DP treatment on the fibrinolitic profile of patients with chronic liver disease, comparing the changes iD dimer markers at basal and 4 weeks after administration | changes in the D dimer (micrograms/L) between groups | at basal visit and month1 |
| Impact of DP treatment comparing the changes in the TAT marker at basal and 4 weeks after administration | changes in the TAT (trombi-antitrombin) (minutes), between groups | at basal visit and month1 |
| Impact of DP treatment comparing the changes in the heptacidin marker at basal and 4 weeks after administration | changes in the hepcidin (nmol/dL), between groups | at basal visit and month1 |
| Impact of DP treatment on the erythropoietin marker at basal and 4 weeks after administration | changes in the erythropoietin (mU/mL) between groups | at basal visit and month1 |
| To explore the impact of anemia on complications of portal hypertension | the number and type of acute decompensations (acute gastrointestinal bleeding, infection,Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0 | through study completion, an average of 1 year |
| To explore the impact of the anemia on the quality of life measured by the EuroQol-5D scale , in both groups. | the quality of life measured by the EuroQol-5D scale of quality of live european | through study completion, an average of 1 year |
| 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. | base line visit, month 1, month 2, month 3, month 6. |
| Proportion of patients and severity of treatment-related adverse events during the study period, | Proportion of patients and severity of treatment-related adverse events during the study period, | through study completion, an average of 1 year |
| D002241 |
| Carbohydrates |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |