Erythroblastosis, FetalPhase 2/3EPO-4-RhesusNCT03104426
EPO-4-Rhesus Study
A Phase 2/3 study testing Darbepoetin Alfa in people with Erythroblastosis, Fetal and Erythroblastosis Fetalis, Rh Disease, run by Sanquin-LUMC J.J van Rood Center for Clinical Transfusion Research at 1 site in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages Up to 2 years
- Conditions the study is for
- Erythroblastosis, Fetal, Erythroblastosis Fetalis, Rh Disease, Erythroblastosis Fetalis Due to RH Antibodies
- What is being tested?
- Darbepoetin Alfa
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- 1 siteNetherlands
- Study dates
- 31 Oct 2017to Aug 2020
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 2 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- all (near)-term neonates (gestational age ≥ 35 weeks) admitted to the Leiden University Medical Center (LUMC) with HDFN, treated with IUT.
Who cannot join
- none.
Trial locations and contacts
1 site in 1 country.
Netherlands1 site, 1 recruiting
- Recruiting
Leiden University Medical Center
Leiden, 2300RC
Enrico Lopriore, MD Phd, E.Lopriore@lumc.nl
About this 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
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.
Read the 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.
- Conditions
- Erythroblastosis, Fetal, Erythroblastosis Fetalis, Rh Disease, Erythroblastosis Fetalis Due to RH Antibodies, Erythroblastosis Fetalis Due to Isoimmunization
- Being tested
- Darbepoetin Alfa
- Keywords
- Hemolytic disease of the fetus and newborn, HDFN, Red blood cell alloimmunization
- Medical subject headings
- Erythroblastosis, Fetal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Darbepoetin AlfaDrug
Also called Aranesp
Darbepoetin alfa dosage 10microg/kg once a week for 8 weeks
| Study group | Role | What they receive |
|---|---|---|
| Darbepoetin alfa group | Active comparator | Group treated with darbepoetin alfa (Aranesp) 10microg/kg once a week for a period of 8 weeks. Receives: Drug: Darbepoetin Alfa |
| Control group | No intervention | "Standard care" which involves close monitoring of hemoglobin levels and if necessary, top-up red cell transfusion. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of top-up transfusions required per infant
Number of top-up transfusions required per infant
Measured: First 3 months of life
Secondary outcomes (4)
The percentage of infants requiring a top-up transfusion
The percentage of infants requiring a top-up transfusion
Measured: First 3 months of life
Number of days of admission for top-up transfusions
Number of days of admission for top-up transfusions
Measured: 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
Measured: 8 weeks (treatment course)
Occurrence of high ferritin levels
The percentage of infants with ferritin levels >200 μg/L during treatment
Measured: 8 weeks (treatment course)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Apr 2017
- Study start31 Oct 2017
- Primary completionAug 2020 (estimated)
- Study completionAug 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Erythroblastosis, FetalStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- RCT with unblinded treatment allocation 1:1 ratio. Either treatment with darbepoetin alfa or "standard care". No placebo.
- Masking
- None (open label)
- Enrolment
- 42 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sanquin-LUMC J.J van Rood Center for Clinical Transfusion Research
- Sponsor type
- University, hospital or other
- Collaborators
- Leiden University Medical Center
- Responsible party
- Sponsor
- Investigators
- Masja de Haas, MD PhD, Principal investigator, Sanquin Research
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03104426
- Sponsor's protocol ID
- P17.102
- Acronym
- EPO-4-Rhesus
- Status last verified
- Sep 2019
- First submitted
- 3 Apr 2017
- Last updated
- 2 Oct 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 38030319
Study at a glance
From the registry record, last updated by the sponsor on 2 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03104426
- Acronym / sponsor ID
- EPO-4-Rhesus / P17.102
- 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
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 42 participants (estimated)
- Lead sponsor
- Sanquin-LUMC J.J van Rood Center for Clinical Transfusion ResearchUniversity, hospital or other
- Collaborators
- Leiden University Medical Center
- Study start
- 31 Oct 2017 (actual)
- Primary completion
- Aug 2020 (estimated)
- Study completion
- Aug 2020 (estimated)
- First posted
- 7 Apr 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- RCT with unblinded treatment allocation 1:1 ratio. Either treatment with darbepoetin alfa or "standard care". No placebo.
| Arm | Type | Receives |
|---|---|---|
| Darbepoetin alfa group | Active comparator | Drug: Darbepoetin AlfaGroup 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. |
Who may qualify
- Ages
- Up to 2 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (1 listed)
- all (near)-term neonates (gestational age ≥ 35 weeks) admitted to the Leiden University Medical Center (LUMC) with HDFN, treated with IUT.
Key exclusion criteria (1 listed)
- none.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Darbepoetin AlfaAlso: AranespDarbepoetin alfa dosage 10microg/kg once a week for 8 weeks | Drug | Darbepoetin alfa group |
Primary outcome
Number of top-up transfusions required per infant
Time frame: First 3 months of life
Number of top-up transfusions required per infant
4 secondary outcomes
The percentage of infants requiring a top-up transfusion
Time frame: First 3 months of life
Number of days of admission for top-up transfusions
Time frame: First 3 months of life
Occurrence of hypertension
Time frame: 8 weeks (treatment course)
Occurrence of high ferritin levels
Time frame: 8 weeks (treatment course)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Oct 2019.
- Derived from this study: PubMed 38030319Ree 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Masja de Haas, MD PhD principal investigator
Sanquin Research
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Darbepoetin Alfa in people with Erythroblastosis, Fetal and Erythroblastosis Fetalis, Rh Disease, run by Sanquin-LUMC J.J van Rood Center for Clinical Transfusion Research at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 2 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Isabelle MC Ree, MD (+31715262814, i.m.c.ree@lumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of top-up transfusions required per infant (time frame: First 3 months of life). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03104426, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Oct 2019.