Darbe + IV Iron for Premature Infants
(DIVI Trial)
Recruiting in Palo Alto (17 mi)
Age: < 18
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: University of Washington
Disqualifiers: Anomalies, High hematocrit, High iron, Infections, others
No Placebo Group
Prior Safety Data
Approved in 4 Jurisdictions
Trial Summary
What is the purpose of this trial?This trial uses Darbepoetin and slow-release IV iron to help preterm infants. The treatment aims to reduce the need for blood transfusions, keep iron levels stable, and support better brain development without causing stomach problems.
Will I have to stop taking my current medications?
The trial protocol does not specify whether participants must stop taking their current medications. It is best to discuss this with the trial coordinators or your healthcare provider.
What data supports the effectiveness of the drug Darbepoetin Alfa (Darbe) combined with IV Iron for premature infants?
Research shows that Darbepoetin Alfa (Darbe) is effective in treating anemia in premature infants and can reduce the need for blood transfusions. Additionally, combining Darbepoetin Alfa with IV iron has been shown to improve treatment response in patients with anemia, suggesting potential benefits for premature infants as well.
12345Is the combination of Darbe and IV Iron safe for premature infants?
Research on IV iron products, including ferumoxytol, shows that adverse events (unwanted effects from the drug) can occur, but specific safety data for premature infants using Darbe and IV Iron is not detailed in the available studies.
678910How is the drug Darbepoetin Alfa (Darbe) unique for treating premature infants?
Darbepoetin Alfa (Darbe) is unique for treating premature infants because it is an erythropoiesis-stimulating agent (ESA) that can potentially reduce the need for blood transfusions with less frequent dosing compared to erythropoietin (Epo), which is commonly used for anemia in adults.
211121314Eligibility Criteria
This trial is for preterm infants born between 24 and almost 32 weeks of gestation. It's open to all eligible NICU patients regardless of sex, race, or ethnicity. Infants with high iron levels, infections at enrollment, significant clinical anomalies, or whose parents cannot consent within 72 hours after birth are excluded.Inclusion Criteria
I understand that eligibility is not based on my sex, race, ethnicity, background, or religion.
My baby was born between 24 and 31 weeks of pregnancy.
Exclusion Criteria
Your blood thickness is higher than normal.
Your blood tests show that you have a lot of iron in your body.
My baby has been diagnosed with a significant health condition.
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Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
1-2 weeks
Treatment
Infants receive Darbepoetin and intravenous iron starting from day 3 and day 7 of life respectively, with doses adjusted based on iron studies
Birth to 36 weeks postmenstrual age
Weekly visits for dose adjustments and monitoring
Follow-up
Participants are monitored for neurodevelopmental outcomes and gut microbiome changes up to 2 years of age
Up to 2 years corrected age
Assessments at 1 year and 2 years corrected age
Long-term Follow-up
Long-term monitoring of neurodevelopmental outcomes and gut microbiome
2 years
Participant Groups
The study tests if Darbepoetin (Darbe) combined with IV iron (Ferumoxytol or low molecular weight iron dextran) can reduce the need for blood transfusions while maintaining sufficient iron levels and improving neurodevelopment in premature infants compared to oral iron supplements.
5Treatment groups
Experimental Treatment
Active Control
Group I: Group 5Experimental Treatment2 Interventions
Infants randomized to this arm will receive Darbe 10 mcg/kg q week started on day 3 of life. In addition, beginning on day 7, they will receive FMX: 20 mg/kg x 1, retreat if ferritin \< 76 mcg/L
Group II: Group 4Experimental Treatment2 Interventions
Infants randomized to this arm will receive Darbe 10 mcg/kg q week started on day 3 of life. In addition, beginning on day 7, they will receive FMX: 10 mg/kg x 1, retreat if ferritin \< 76 mcg/L
Group III: Group 3Experimental Treatment2 Interventions
Infants randomized to this arm will receive Darbe 10 mcg/kg q week started on day 3 of life. In addition, beginning on day 7, they will receive LMW-ID: 20 mg/kg x 1, retreat if ferritin \< 76 mcg/L
Group IV: Group 2Experimental Treatment2 Interventions
Infants randomized to this arm will receive Darbe 10 mcg/kg q week started on day 3 of life. In addition, beginning on day 7, they will receive LMW-ID: 10 mg/kg x 1, retreat if ferritin \< 76 mcg/L
Group V: Group 1. Oral ironActive Control1 Intervention
Oral iron is started on day 7 of life if baby is feeding 100 mL/kg/day. Iron supplements of up to 12 mg/kg/day are given based on CBC, retic, ret-hgb, serum ferritin and zinc protoporphyrin to heme ratio (ZnPP/H). Iron supplements are adjusted every 2 weeks following iron studies.
Darbepoetin Alfa is already approved in European Union, United States, Canada, Japan for the following indications:
🇪🇺 Approved in European Union as Aranesp for:
- Anemia associated with chronic kidney disease
- Anemia in adult cancer patients with non-myeloid malignancies
🇺🇸 Approved in United States as Aranesp for:
- Anemia associated with chronic kidney disease
- Anemia in patients with non-myeloid malignancies where anemia is due to concomitantly administered chemotherapy
🇨🇦 Approved in Canada as Aranesp for:
- Anemia associated with chronic kidney disease
- Anemia in patients with non-myeloid malignancies where anemia is due to concomitantly administered chemotherapy
🇯🇵 Approved in Japan as Aranesp for:
- Anemia associated with chronic kidney disease
- Anemia in patients with non-myeloid malignancies where anemia is due to concomitantly administered chemotherapy
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of WashingtonSeattle, WA
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Who Is Running the Clinical Trial?
University of WashingtonLead Sponsor
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)Collaborator
References
Darbepoetin Administration in Term and Preterm Neonates. [2018]Erythropoiesis-stimulating agents (ESAs) such as erythropoietin have been studied as red cell growth factors in preterm and term infants for more than 20 years. Recent studies have evaluated darbepoetin (Darbe, a long-acting ESA) for both erythropoietic effects and potential neuroprotection. We review clinical trials of Darbe in term and preterm infants, which have reported significant erythropoietic uses and neuroprotective effects. ESAs show great promise in decreasing or eliminating transfusions, and in preventing and treating brain injury in term and preterm infants.
Darbepoetin alfa 300 or 500 μg once every 3 weeks with or without intravenous iron in patients with chemotherapy-induced anemia. [2015]This study evaluated efficacy and safety of darbepoetin alfa administered every 3 weeks (Q3W) at fixed doses of 300 or 500 μg with or without intravenous (IV) iron in treating anemia in patients receiving multicycle chemotherapy. This Phase 2, double-blind, 2 × 2 factorial study randomized patients to one of four treatment arms; darbepoetin alfa 300 μg (n = 62), darbepoetin alfa 300 μg plus IV iron (n = 60), darbepoetin alfa 500 μg (n = 60), or darbepoetin alfa 500 μg plus IV iron (n = 60). Patients had nonmyeloid malignancies, hemoglobin levels ≤10 g dL(-1), and no iron deficiency. Primary endpoint was achievement of target hemoglobin (≥11 g dL(-1)). Secondary endpoints included incidence of transfusions and change in Functional Assessment of Cancer Therapy Fatigue (FACT-F) score from baseline to end of study. Safety was evaluated by incidence of adverse events. No evidence of a statistically significant interaction between darbepoetin alfa dose received and IV iron usage was observed, therefore, results are provided separately comparing darbepoetin alfa doses and comparing IV iron usage groups. Similar proportions of patients receiving darbepoetin alfa 300 or 500 μg achieved target hemoglobin (75 and 78%, respectively); Kaplan-Meier median time to target hemoglobin was 10 and 8 weeks, respectively. More patients receiving IV iron (82%) than not receiving IV iron (72%) achieved hemoglobin target. Adverse events profiles were similar for darbepoetin alfa treatment groups. Transient anaphylactoid reactions were reported in two patients receiving IV iron. Darbepoetin alfa at 300 μg Q3W and 500 μg Q3W showed similar benefit, while added IV iron improved treatment response in these patients.
Characterization of Neutropenia in Preterm Neonates Following Administration of Darbepoetin Alfa. [2023]This study is to evaluate the effects of darbepoetin alfa (darbe) on neutrophil count in preterm neonates treated for anemia of prematurity.
Darbepoetin as a neuroprotective agent in mild neonatal encephalopathy: a randomized, placebo-controlled, feasibility trial. [2023]To assess the feasibility and safety of one dose of Darbepoetin alpha (Darbe) administered to neonates ≥34 weeks with mild neonatal encephalopathy (NE).
Darbepoetin Alfa for Late-onset Anemia in Neonates with Rhesus Hemolytic Disease. [2023]Neonates with Rhesus hemolytic disease can present with anemia beyond 1 wk of age due to bone marrow suppression and low erythropoietin secretion. Erythropoietin stimulating agents (ESA) were tried to manage anemia in these neonates. Darbepoetin alfa (DA) is a long-acting ESA used to treat anemia in premature neonates and in children with chronic kidney disease or on cancer chemotherapy. The authors present their experience of using DA to treat late-onset hyporegenerative anemia in 3 neonates with Rhesus isoimmunization. Darbepoetin alfa 4 mcg/kg was given subcutaneously at a 1-2-wk interval to target hemoglobin of 10-12 g/dL. No adverse effects were observed, and the treated infants had a reduced need for the packed red blood cell transfusions.
Comparison of rates of reported adverse events associated with i.v. iron products in the United States. [2022]An analysis of reported adverse events (AEs) among patients using i.v. iron products, including the newer agent ferumoxytol, is presented.
Reported adverse drug events in infants and children under 2 years of age. [2022]To characterize risks to infants and young children from drugs and biological products that were identified in spontaneous adverse event reports submitted to the US Food and Drug Administration.
Characterization of adverse drug events identified by trigger in Brazilian pediatric inpatients. [2022]To describe the frequency and characteristics of adverse drug events in pediatric inpatients in a Brazilian tertiary teaching hospital.
Adverse drug reaction-related admissions in paediatrics, a prospective single-centre study. [2021]To investigate the incidence and characteristics of hospital admissions related to adverse drug events in the paediatric setting.
Adverse drug events in children during hospitalization and after discharge in a Norwegian university hospital. [2019]The frequency and characteristics of adverse drug events (ADEs) in children hospitalized in the paediatric department of Ullevaal University Hospital, Norway, were determined using intensive monitoring. Of 579 children treated with drugs, 28% experienced ADEs; 7% at the time of admission, 18% during hospitalization and 9% after discharge. All children treated for cancer, 19% treated with anti-infective drugs, 15% treated with antiasthmatics and 10% treated with drugs affecting the nervous system experienced ADEs. The most frequent events were gastrointestinal, CNS- and skin reactions and 19% were considered as serious. ADEs caused 6% of the admissions and 44% required interventions. Most ADEs were found by screening patient records, where physicians mostly described adverse drug events requiring interventions and nurses described less serious events. Parents reported 14% of the events, of which a majority were CNS reactions. CNS reactions may be more common than expected and observations by parents are important when investigating such reactions in children.
Double-blind, placebo-controlled, randomized phase III trial of darbepoetin alfa in lung cancer patients receiving chemotherapy. [2022]Patients receiving chemotherapy often develop anemia. Darbepoetin alfa (Aranesp(TM)) is an erythropoiesis-stimulating glycoprotein that has been shown, in dose-finding studies, to be safe and clinically active when administered to patients with cancer every 1, 2, or 3 weeks. This phase III study compared the safety and efficacy of darbepoetin alfa with placebo in patients with lung cancer receiving chemotherapy.
A trial of subcutaneous administration of darbepoetin alfa once every other week for the treatment of anemia in peritoneal dialysis patients. [2015]Darbepoetin alfa (Aranesp, Amgen) is an erythropoietic stimulating protein with a three fold longer terminal half life than recombinant human erythropoietin (rHuEPO). The purpose of this single center, single arm study was to determine whether darbepoetin alfa is as effective as rHuEPO for the treatment of renal anemia in patients on peritoneal dialysis when administered at a reduced dosing frequency of once every other week irrespective of the initial rHuEPO dose frequency.
Randomized, multicenter, controlled trial comparing the efficacy and safety of darbepoetin alpha administered every 3 weeks with or without intravenous iron in patients with chemotherapy-induced anemia. [2015]The concomitant use of intravenous (IV) iron as a supplement to erythropoiesis-stimulating agents in patients with chemotherapy-induced anemia is controversial. This study was designed to evaluate the efficacy and safety of darbepoetin alpha given with IV iron versus with local standard practice (oral iron or no iron).
A randomized, masked, placebo-controlled study of darbepoetin alfa in preterm infants. [2021]A novel erythropoiesis stimulating agent (ESA), darbepoetin alfa (Darbe), increases hematocrit in anemic adults when administered every 1 to 3 weeks. Weekly Darbe dosing has not been evaluated in preterm infants. We hypothesized that infants would respond to Darbe by decreasing transfusion needs compared with placebo, with less-frequent dosing than erythropoietin (Epo).