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

Primary Purpose

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

Status
Unknown status
Phase
Phase 2
Locations
Netherlands
Study Type
Interventional
Intervention
Darbepoetin Alfa
Sponsored by
Sanquin-LUMC J.J van Rood Center for Clinical Transfusion Research
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Erythroblastosis, Fetal focused on measuring Hemolytic disease of the fetus and newborn, HDFN, Red blood cell alloimmunization

Eligibility Criteria

undefined - 2 Years (Child)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Leiden University Medical CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

No Intervention

Arm Label

Darbepoetin alfa group

Control group

Arm Description

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

"Standard care" which involves close monitoring of hemoglobin levels and if necessary, top-up red cell transfusion.

Outcomes

Primary Outcome Measures

Number of top-up transfusions required per infant
Number of top-up transfusions required per infant

Secondary Outcome Measures

The percentage of infants requiring a top-up transfusion
The percentage of infants requiring a top-up transfusion
Number of days of admission for top-up transfusions
Number of days of admission for top-up transfusions
Occurrence of hypertension
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
The percentage of infants with ferritin levels >200 μg/L during treatment

Full Information

First Posted
April 3, 2017
Last Updated
September 30, 2019
Sponsor
Sanquin-LUMC J.J van Rood Center for Clinical Transfusion Research
Collaborators
Leiden University Medical Center
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1. Study Identification

Unique Protocol Identification Number
NCT03104426
Brief Title
EPO-4-Rhesus Study
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2019
Overall Recruitment Status
Unknown status
Study Start Date
October 31, 2017 (Actual)
Primary Completion Date
August 2020 (Anticipated)
Study Completion Date
August 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sanquin-LUMC J.J van Rood Center for Clinical Transfusion Research
Collaborators
Leiden University Medical Center

4. Oversight

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
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Model Description
RCT with unblinded treatment allocation 1:1 ratio. Either treatment with darbepoetin alfa or "standard care". No placebo.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
42 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Darbepoetin alfa group
Arm Type
Active Comparator
Arm Description
Group treated with darbepoetin alfa (Aranesp) 10microg/kg once a week for a period of 8 weeks.
Arm Title
Control group
Arm Type
No Intervention
Arm Description
"Standard care" which involves close monitoring of hemoglobin levels and if necessary, top-up red cell transfusion.
Intervention Type
Drug
Intervention Name(s)
Darbepoetin Alfa
Other Intervention Name(s)
Aranesp
Intervention Description
Darbepoetin alfa dosage 10microg/kg once a week for 8 weeks
Primary Outcome Measure Information:
Title
Number of top-up transfusions required per infant
Description
Number of top-up transfusions required per infant
Time Frame
First 3 months of life
Secondary Outcome Measure Information:
Title
The percentage of infants requiring a top-up transfusion
Description
The percentage of infants requiring a top-up transfusion
Time Frame
First 3 months of life
Title
Number of days of admission for top-up transfusions
Description
Number of days of admission for top-up transfusions
Time Frame
First 3 months of life
Title
Occurrence of hypertension
Description
The percentage of infants with a systolic blood pressure ≥ 2 SD above age adjusted mean systolic blood pressure during treatment
Time Frame
8 weeks (treatment course)
Title
Occurrence of high ferritin levels
Description
The percentage of infants with ferritin levels >200 μg/L during treatment
Time Frame
8 weeks (treatment course)
Other Pre-specified Outcome Measures:
Title
Long-term neurodevelopmental outcome
Description
Exploratory outcome; Long-term neurodevelopmental outcome at 2 years of age using the BSID-III test
Time Frame
2 years of age

10. Eligibility

Sex
All
Maximum Age & Unit of Time
2 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Isabelle MC Ree, MD
Phone
+31715262814
Email
i.m.c.ree@lumc.nl
First Name & Middle Initial & Last Name or Official Title & Degree
Enrico Lopriore, MD PhD
Phone
+31715262965
Email
e.lopriore@lumc.nl
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Masja de Haas, MD PhD
Organizational Affiliation
Sanquin Research
Official's Role
Principal Investigator
Facility Information:
Facility Name
Leiden University Medical Center
City
Leiden
ZIP/Postal Code
2300RC
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Enrico Lopriore, MD Phd
Email
E.Lopriore@lumc.nl

12. IPD Sharing Statement

Plan to Share IPD
No

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EPO-4-Rhesus Study

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