EPO-4-Rhesus Study

Erythroblastosis, Fetal Clinical Trial

— EPO-4-Rhesus  

Official title:

Randomized Controlled Trial on the Use of EPO to Reduce Top-up Transfusions in Neonates With Red Blood Cell Alloimmunization Treated With Intrauterine Transfusions

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03104426
• Other study ID #: P17.102
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: October 31, 2017
• Est. completion date: August 2020

Study information

• Verified date: September 2019
• Source: Sanquin-LUMC J.J van Rood Center for Clinical Transfusion Research
• Contact: Isabelle MC Ree, MD
• Phone: +31715262814
• Email: i.m.c.ree[@]lumc.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 42
• Est. completion date: August 2020
• Est. primary completion date: August 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 2 Years

Eligibility

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.

Related Conditions & MeSH terms

• Erythroblastosis Fetalis Due to Isoimmunization
• Erythroblastosis Fetalis Due to RH Antibodies
• Erythroblastosis Fetalis, Rh Disease
• Erythroblastosis, Fetal

Intervention

Drug:
• Darbepoetin Alfa
Darbepoetin alfa dosage 10microg/kg once a week for 8 weeks

Locations

Country	Name	City	State
Netherlands	Leiden University Medical Center	Leiden

Sponsors (2)

Lead Sponsor	Collaborator
Sanquin-LUMC J.J van Rood Center for Clinical Transfusion Research	Leiden University Medical Center

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Long-term neurodevelopmental outcome	Exploratory outcome; Long-term neurodevelopmental outcome at 2 years of age using the BSID-III test	2 years of age
Primary	Number of top-up transfusions required per infant	Number of top-up transfusions required per infant	First 3 months of life
Secondary	The percentage of infants requiring a top-up transfusion	The percentage of infants requiring a top-up transfusion	First 3 months of life
Secondary	Number of days of admission for top-up transfusions	Number of days of admission for top-up transfusions	First 3 months of life
Secondary	Occurrence of hypertension	The percentage of infants with a systolic blood pressure = 2 SD above age adjusted mean systolic blood pressure during treatment	8 weeks (treatment course)
Secondary	Occurrence of high ferritin levels	The percentage of infants with ferritin levels >200 µg/L during treatment	8 weeks (treatment course)