EPO-4-Rhesus Study

Phase 2

• Conditions: Erythroblastosis, Fetal; Erythroblastosis Fetalis, Rh Disease; Erythroblastosis Fetalis Due to RH Antibodies; Erythroblastosis Fetalis Due to Isoimmunization
• Interventions: Drug: Darbepoetin Alfa

• Registration Number: NCT03104426
• Lead Sponsor: Sanquin-LUMC J.J van Rood Center for Clinical Transfusion Research

Brief Summary

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.

Detailed 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.

Study Timeline

• Study First Submitted: 2017-04-03
• Study First Submitted QC: 2017-04-03
• Study First Posted: 2017-04-07
• Study Start: 2017-10-31
• Status Verified: 2019-09
• Last Update Submitted: 2019-09-30
• Last Update Posted: 2019-10-02
• Primary Completion: 2020-08
• Study Completion: 2020-08

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 42

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
Number of top-up transfusions required per infant	First 3 months of life	Number of top-up transfusions required per infant

Secondary Outcome Measures

Name	Time	Method
The percentage of infants requiring a top-up transfusion	First 3 months of life	The percentage of infants requiring a top-up transfusion
Number of days of admission for top-up transfusions	First 3 months of life	Number of days of admission for top-up transfusions
Occurrence of hypertension	8 weeks (treatment course)	The percentage of infants with a systolic blood pressure ≥ 2 SD above age adjusted mean systolic blood pressure during treatment
Occurrence of high ferritin levels	8 weeks (treatment course)	The percentage of infants with ferritin levels \>200 μg/L during treatment

Trial Locations

Locations (1)

Leiden University Medical Center; 🇳🇱 Leiden, Netherlands