Clinical trial NCT03104426: EPO-4-Rhesus Study
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Erythroblastosis, Fetal
Erythroblastosis Fetalis, Rh Disease
Erythroblastosis Fetalis Due to RH Antibodies
Erythroblastosis Fetalis Due to Isoimmunization
Keywords: Hemolytic disease of the fetus and newborn
HDFN
Red blood cell alloimmunization
Lead sponsor: Sanquin-LUMC J.J van Rood Center for Clinical Transfusion Research
Sponsor class: OTHER
Collaborators: name: Leiden University Medical Center
First posted: 2017-04-07
Enrollment: 42
Sex: ALL
Maximum age (years): 2
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: RCT with unblinded treatment allocation 1:1 ratio. Either treatment with darbepoetin alfa or "standard care". No placebo.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of top-up transfusions required per infant
timeFrame: First 3 months of life
Secondary outcomes:
measure: The percentage of infants requiring a top-up transfusion
timeFrame: First 3 months of life
measure: Number of days of admission for top-up transfusions
timeFrame: First 3 months of life
measure: Occurrence of hypertension
timeFrame: 8 weeks (treatment course)
measure: Occurrence of high ferritin levels
timeFrame: 8 weeks (treatment course)
Other outcomes:
measure: Long-term neurodevelopmental outcome
timeFrame: 2 years of age
Locations:
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
Study officials:
affiliation: Sanquin Research
name: Masja de Haas, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: