EPO-4-Rhesus Study

Sanquin-LUMC J.J van Rood Center for Clinical Transfusion Research

Status and phase: Unknown; Phase 3; Phase 2

Conditions: Erythroblastosis Fetalis, Rh Disease; Erythroblastosis, Fetal; Erythroblastosis Fetalis Due to Isoimmunization; Erythroblastosis Fetalis Due to RH Antibodies

Treatments: Drug: Darbepoetin Alfa

Study type: Interventional

Funder types: Other

Identifiers

NCT03104426

P17.102

Details and patient eligibility

About

Up to 80% of infants with hemolytic disease due to maternal alloimmunization, treated with IUT, require at least one top-up transfusion for late anemia during the first 3 months of life. Erythropoietin deficiency is also considered as a possible contributing factor to late anemia and therefore we will assess the role of EPO (darbepoetin alfa) in the treatment of these infants.

Full description

The mainstay of antenatal treatment of fetal anemia due to red cell alloimmunization is (serial) IUT. The mainstay of postnatal treatment in HDN is (1) intensive phototherapy and exchange transfusion to treat hyperbilirubinemia and prevent kernicterus, and (2) top-up transfusions to treat anemia. Up to 80% of infants with HDN treated with IUT require at least one top-up transfusion for late anemia during the first 3 months of life.

Several risk factors for late anemia have been reported, including serial IUT (due to bone marrow suppression), severity of HDN, reduced use of exchange transfusions during the neonatal period and reduced survival of transfused red blood cells. Finally, erythropoietin deficiency is also considered as a possible contributing factor to late anemia.

EPO has been increasingly used in neonates to prevent or reduce neonatal anemia without short or long-term adverse effects. Several small studies and casuistic reports suggest that neonates with HDN may benefit from treatment with EPO to reduce the risk of delayed anemia and subsequent top-up transfusions. However, other authors found that EPO may be less effective than expected. Due to the lack of evidence, routine use of EPO is currently not recommended. To determine a role for EPO in this group of patients, a well-designed randomized controlled clinical trial of sufficient sample size is required. Potentially, EPO stabilizes the hemoglobin levels of these infants and thus prevents top-up transfusions and extra admissions, creating a more stable and natural postnatal course for patients with HDN.

Enrollment: 42 estimated patients

Sex: All

Ages: Under 2 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• all (near)-term neonates (gestational age ≥ 35 weeks) admitted to the Leiden University Medical Center (LUMC) with HDFN, treated with IUT.

Exclusion criteria

• none.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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42 participants in 2 patient groups

Darbepoetin alfa group

Active Comparator group

Description:

Group treated with darbepoetin alfa (Aranesp) 10microg/kg once a week for a period of 8 weeks.

Treatment:

Drug: Darbepoetin Alfa

Control group

No Intervention group

Description:

"Standard care" which involves close monitoring of hemoglobin levels and if necessary, top-up red cell transfusion.