Darbepoetin for Preterm Infants

(Darbe Trial)

No longer recruiting at 15 trial locations

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: NICHD Neonatal Research Network

Must not be taking: Epo, Darbe

Disqualifiers: Congenital anomalies, Seizures, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 22

Duration: 9 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether Darbepoetin can improve brain development in preterm infants by the time they reach 22 to 26 months old. Researchers administer Darbepoetin to some infants while others receive a placebo (a harmless substitute) to compare outcomes. The trial seeks preterm infants born between 23 and 28 weeks of pregnancy who are less than 24 hours old. Participants must not have certain medical conditions, such as high blood pressure or brain anomalies, and must be available for follow-up. As a Phase 3 trial, this study represents the final step before FDA approval, offering a chance to contribute to potentially groundbreaking treatment for preterm infants.

Will I have to stop taking my current medications?

The trial information does not specify whether participants must stop taking their current medications.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that Darbepoetin is safe for use in both full-term and premature babies. Studies have found it is usually well-tolerated, and evidence suggests it might help protect the brain. However, more research is needed to confirm these brain-protective effects.

Regarding safety, past clinical studies have not identified any major safety issues with Darbepoetin in newborns. It has reduced the need for blood transfusions in very premature babies, but it does not appear to improve mental development or thinking skills.

Overall, Darbepoetin is considered safe, but like any medical treatment, there may be risks. Discussing these with a healthcare provider is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for preterm infants?

Darbepoetin is unique because it's a synthetic version of erythropoietin, a hormone that helps produce red blood cells. This is particularly exciting for treating preterm infants who often suffer from anemia. Unlike standard treatments that might involve blood transfusions with their associated risks, darbepoetin offers a non-invasive option that can be administered through an IV or injection. Researchers are excited about its potential to safely boost red blood cell production, reducing the need for transfusions and enhancing the overall care of these vulnerable infants.

What evidence suggests that Darbepoetin might be an effective treatment for preterm infants?

In this trial, participants will receive either darbepoetin or a placebo. Research suggests that darbepoetin may reduce the need for blood transfusions in preterm infants. However, studies have shown mixed results regarding its impact on brain development in these infants. Some research found that similar treatments with drugs stimulating red blood cell production led to better brain development. Yet, a specific study on darbepoetin showed no significant improvement in brain development. While it may help reduce the need for transfusions, its effectiveness in supporting brain growth remains uncertain. ^{1 3 4 6 7}

Who Is on the Research Team?

Robin Ohls, MD

Principal Investigator

University of Utah

Are You a Good Fit for This Trial?

This trial is for preterm infants born between 23 and nearly 29 weeks of gestation, who are less than one day old. It's not for babies with genetic or heart defects, brain anomalies, high blood count, seizures, clotting disorders, very high blood pressure without medication support, or if they're already getting similar treatments.

Inclusion Criteria

23 0/7-28 6/7 weeks gestation

My baby is less than 24 hours old.

My baby was born prematurely.

Exclusion Criteria

I have a bleeding or blood disorder.

Hematocrit > 60%

Congenital thrombotic disease

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Preterm infants receive weekly Darbepoetin or placebo during the neonatal period

9 weeks

Weekly visits for dosing

Follow-up

Participants are monitored for safety and effectiveness after treatment

22-26 months

Visits at 22-26 months corrected age

Extended follow-up

Subjects will be seen for follow-up at 4-5 years and 6-7 years corrected age to assess long-term outcomes

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Darbepoetin
• Placebo

Trial Overview The study tests whether giving Darbepoetin (Darbe) to premature babies weekly can improve their brain development and cognitive skills by the time they're about two years old. They'll compare results from babies given Darbe against those given a placebo.

How Is the Trial Designed?

Group I: Darbepoetin Experimental Treatment 1 Intervention

Darbepoetin 10 micrograms/kg/once every week (IV or SC)

Group II: Placebo Placebo Group 1 Intervention

Equal volume normal saline for IV administration, or sham dosing

Who Is Running the Clinical Trial?

NICHD Neonatal Research Network

Lead Sponsor

Trials

62

Recruited

209,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Published Research Related to This Trial

Darbepoetin alfa (DA) was safely administered to 3 neonates with Rhesus isoimmunization to treat late-onset anemia, with no adverse effects reported.

The treatment with DA reduced the need for packed red blood cell transfusions, indicating its efficacy in managing anemia in these infants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Darbepoetin Alfa for Late-onset Anemia in Neonates with Rhesus Hemolytic Disease. Rv, S., S, R.[2023]

The study assessed the safety and feasibility of administering a single dose of Darbepoetin alpha (Darbe) to 21 neonates with mild neonatal encephalopathy, and found no adverse events reported in either the Darbe or placebo groups.

Both groups showed average developmental scores on the Bayley Scales of Infant and Toddler Development, indicating that while the treatment was safe, further large-scale trials are needed to evaluate the efficacy of Darbe in improving outcomes for these infants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Darbepoetin as a neuroprotective agent in mild neonatal encephalopathy: a randomized, placebo-controlled, feasibility trial. DuPont, TL., Baserga, M., Lowe, J., et al.[2023]

In a study involving 90 preterm neonates (45 treated with darbepoetin alfa and 45 controls), the administration of darbepoetin alfa did not significantly affect neutrophil counts or the rates of neutropenia compared to the control group.

There were no differences in the occurrence of neutropenia (ANC ≤1000/μL) or severe neutropenia (ANC ≤500/μL) between the darbe-treated and control neonates, indicating that darbepoetin alfa does not impact neutrophil levels in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization of Neutropenia in Preterm Neonates Following Administration of Darbepoetin Alfa. Andrews, N., Friedman, S., Dunham, M., et al.[2023]

Darbepoetin, a long-acting erythropoiesis-stimulating agent (ESA), has shown significant effectiveness in promoting red blood cell production in both term and preterm infants, potentially reducing the need for blood transfusions.

In addition to its erythropoietic effects, darbepoetin may also offer neuroprotective benefits, helping to prevent and treat brain injuries in infants, which highlights its dual role in neonatal care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Darbepoetin Administration in Term and Preterm Neonates. Patel, S., Ohls, RK.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4531269/

Cognitive Outcomes of Preterm Infants Randomized to ... Infants randomized to receive ESAs had better cognitive outcomes, compared with placebo recipients, at 18 to 22 months.

2. rti.org rti.org/announcements/darbepoetin-preterm-infants-cognitive-outcomes-study

Study Finds Darbepoetin Doesn't Boost Preterm Cognitive ... New JAMA Pediatrics study found darbepoetin lowers blood transfusions in extremely preterm infants but does not improve cognitive outcomes ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03169881

NCT03169881 | Darbepoetin Trial to Improve Red Cell ... Study Overview. Advances in neonatal care have led to significant improvements in the survival of the nearly 60,000 very low birth weight (VLBW) infants born ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4529960/

Darbepoetin administration in Term and Preterm Neonates Darbe shows great promise in decreasing or eliminating transfusions in neonates, and in preventing and treating brain injury in term and preterm infants.

5. hopkinsmedicine.org hopkinsmedicine.org/-/media/files/allchildrens/clinical-pathways/darbepoetin-use-in-the-management-of-anemia-of-prematurity.pdf

darbepoetin-use-in-the-management-of-anemia-of- ... Darbepoetin alfa is a longer acting ESA, has been used in preterm infants using a weekly dose of 10 mcg/kg (12). Overall, fewer injections are ...

6. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2799123

Safety and Short-term Outcomes of High-Dose ... Up to TEA, 10 newborns died (16.7%) in the erythropoietin group, and 5 newborns (8.2%) died in the placebo group (adjusted odds ratio, 2.24 [95% ...

7. nejm.org nejm.org/doi/full/10.1056/NEJMoa1907423

A Randomized Trial of Erythropoietin for Neuroprotection in ... In summary, we did not observe that treatment with high-dose erythropoietin in extremely preterm infants resulted in a lower risk of death or in ...