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EPO-4-Rhesus Study (EPO-4-Rhesus)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03104426
Recruitment Status : Unknown
Verified September 2019 by Sanquin-LUMC J.J van Rood Center for Clinical Transfusion Research.
Recruitment status was:  Recruiting
First Posted : April 7, 2017
Last Update Posted : October 2, 2019
Sponsor:
Collaborator:
Leiden University Medical Center
Information provided by (Responsible Party):
Sanquin-LUMC J.J van Rood Center for Clinical Transfusion Research

Study Description
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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.

Condition or disease Intervention/treatment Phase
Erythroblastosis, Fetal Erythroblastosis Fetalis, Rh Disease Erythroblastosis Fetalis Due to RH Antibodies Erythroblastosis Fetalis Due to Isoimmunization Drug: Darbepoetin Alfa Phase 2 Phase 3

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 Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 42 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: RCT with unblinded treatment allocation 1:1 ratio. Either treatment with darbepoetin alfa or "standard care". No placebo.
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : October 31, 2017
Estimated Primary Completion Date : August 2020
Estimated Study Completion Date : August 2020

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Active Comparator: Darbepoetin alfa group
Group treated with darbepoetin alfa (Aranesp) 10microg/kg once a week for a period of 8 weeks.
 Drug: Darbepoetin Alfa
Darbepoetin alfa dosage 10microg/kg once a week for 8 weeks
Other Name: Aranesp
No Intervention: Control group
"Standard care" which involves close monitoring of hemoglobin levels and if necessary, top-up red cell transfusion.


Outcome Measures
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Primary Outcome Measures :
  1. Number of top-up transfusions required per infant [ Time Frame: First 3 months of life ]
    Number of top-up transfusions required per infant


Secondary Outcome Measures :
  1. The percentage of infants requiring a top-up transfusion [ Time Frame: First 3 months of life ]
    The percentage of infants requiring a top-up transfusion

  2. Number of days of admission for top-up transfusions [ Time Frame: First 3 months of life ]
    Number of days of admission for top-up transfusions

  3. Occurrence of hypertension [ Time Frame: 8 weeks (treatment course) ]
    The percentage of infants with a systolic blood pressure ≥ 2 SD above age adjusted mean systolic blood pressure during treatment

  4. Occurrence of high ferritin levels [ Time Frame: 8 weeks (treatment course) ]
    The percentage of infants with ferritin levels >200 μg/L during treatment


Other Outcome Measures:
  1. Long-term neurodevelopmental outcome [ Time Frame: 2 years of age ]
    Exploratory outcome; Long-term neurodevelopmental outcome at 2 years of age using the BSID-III test


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   up to 2 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03104426


Contacts
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Contact: Isabelle MC Ree, MD +31715262814 i.m.c.ree@lumc.nl
Contact: Enrico Lopriore, MD PhD +31715262965 e.lopriore@lumc.nl

Locations
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Netherlands
Leiden University Medical Center Recruiting
Leiden, Netherlands, 2300RC
Contact: Enrico Lopriore, MD Phd       E.Lopriore@lumc.nl   
Sponsors and Collaborators
Sanquin-LUMC J.J van Rood Center for Clinical Transfusion Research
Leiden University Medical Center
Investigators
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Principal Investigator: Masja de Haas, MD PhD Sanquin Research
  Study Documents (Full-Text)

Documents provided by Sanquin-LUMC J.J van Rood Center for Clinical Transfusion Research:
Study Protocol  [PDF] April 26, 2018
Statistical Analysis Plan  [PDF] September 14, 2018

More Information
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Responsible Party: Sanquin-LUMC J.J van Rood Center for Clinical Transfusion Research
ClinicalTrials.gov Identifier: NCT03104426    
Other Study ID Numbers: P17.102
First Posted: April 7, 2017    Key Record Dates
Last Update Posted: October 2, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Sanquin-LUMC J.J van Rood Center for Clinical Transfusion Research:
Hemolytic disease of the fetus and newborn
HDFN
Red blood cell alloimmunization
Additional relevant MeSH terms:
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Erythroblastosis, Fetal
Fetal Diseases
Pregnancy Complications
Female Urogenital Diseases and Pregnancy Complications
Urogenital Diseases
 Hematologic Diseases
Infant, Newborn, Diseases
Immune System Diseases
Darbepoetin alfa
Hematinics