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| Name | Class |
|---|---|
| Leiden University Medical Center | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Darbepoetin alfa group | Active Comparator | Group treated with darbepoetin alfa (Aranesp) 10microg/kg once a week for a period of 8 weeks. |
|
| Control group | No Intervention | "Standard care" which involves close monitoring of hemoglobin levels and if necessary, top-up red cell transfusion. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Darbepoetin Alfa | Drug | Darbepoetin alfa dosage 10microg/kg once a week for 8 weeks |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of top-up transfusions required per infant | Number of top-up transfusions required per infant | First 3 months of life |
| Measure | Description | Time Frame |
|---|---|---|
| The percentage of infants requiring a top-up transfusion | The percentage of infants requiring a top-up transfusion | First 3 months of life |
| Number of days of admission for top-up transfusions | Number of days of admission for top-up transfusions |
| Measure | Description | Time Frame |
|---|---|---|
| Long-term neurodevelopmental outcome | Exploratory outcome; Long-term neurodevelopmental outcome at 2 years of age using the BSID-III test | 2 years of age |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Isabelle MC Ree, MD | Contact | +31715262814 | i.m.c.ree@lumc.nl | |
| Enrico Lopriore, MD PhD | Contact | +31715262965 | e.lopriore@lumc.nl |
| Name | Affiliation | Role |
|---|---|---|
| Masja de Haas, MD PhD | Sanquin Research | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Leiden University Medical Center | Recruiting | Leiden | 2300RC | Netherlands |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38030319 | Derived | Ree IMC, de Haas M, van Geloven N, Juul SE, de Winter D, Verweij EJT, Oepkes D, van der Bom JG, Lopriore E. Darbepoetin alfa to reduce transfusion episodes in infants with haemolytic disease of the fetus and newborn who are treated with intrauterine transfusions in the Netherlands: an open-label, single-centre, phase 2, randomised, controlled trial. Lancet Haematol. 2023 Dec;10(12):e976-e984. doi: 10.1016/S2352-3026(23)00285-5. |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Apr 26, 2018 | Sep 14, 2018 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Sep 14, 2018 | Sep 14, 2018 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D004899 | Erythroblastosis, Fetal |
| ID | Term |
|---|---|
| D005315 | Fetal Diseases |
| D011248 | Pregnancy Complications |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
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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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RCT with unblinded treatment allocation 1:1 ratio. Either treatment with darbepoetin alfa or "standard care". No placebo.
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| First 3 months of life |
| 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) |
| Occurrence of high ferritin levels | The percentage of infants with ferritin levels >200 μg/L during treatment | 8 weeks (treatment course) |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D007232 | Infant, Newborn, Diseases |
| D007154 | Immune System Diseases |
| D002241 |
| Carbohydrates |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |