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

• ClinicalTrials.gov Identifier: NCT03104426
• Recruitment Status: Unknown
• First Posted: April 7, 2017
• Last Update Posted: October 2, 2019
• Sponsor: Sanquin-LUMC J.J van Rood Center for Clinical Transfusion Research
• Collaborator: Leiden University Medical Center
• Information provided by (Responsible Party): Sanquin-LUMC J.J van Rood Center for Clinical Transfusion Research

Tracking Information

• First Submitted Date: April 3, 2017
• First Posted Date: April 7, 2017
• Last Update Posted Date: October 2, 2019
• Actual Study Start Date: October 31, 2017
• Estimated Primary Completion Date: August 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 3, 2017)

Number of top-up transfusions required per infant [ Time Frame: First 3 months of life ]

Number of top-up transfusions required per infant

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 3, 2017)

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

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: April 3, 2017)

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

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: 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
• 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.

• Study Type: Interventional
• Study Phase: Phase 2; Phase 3

Study Design

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

Condition

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

Intervention

Drug: Darbepoetin Alfa

Darbepoetin alfa dosage 10microg/kg once a week for 8 weeks

Other Name: Aranesp

Study Arms

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

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: April 3, 2017): 42
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: August 2020
• Estimated Primary Completion Date: August 2020 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: up to 2 Years (Child)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Netherlands

Administrative Information

• NCT Number: NCT03104426
• Other Study ID Numbers: P17.102
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Sanquin-LUMC J.J van Rood Center for Clinical Transfusion Research
• Original Responsible Party: Same as current
• Current Study Sponsor: Sanquin-LUMC J.J van Rood Center for Clinical Transfusion Research
• Original Study Sponsor: Same as current
• Collaborators: Leiden University Medical Center

Investigators

• Principal Investigator: Masja de Haas, MD PhD; Sanquin Research

• PRS Account: Sanquin-LUMC J.J van Rood Center for Clinical Transfusion Research
• Verification Date: September 2019