Darbepoetin Trial to Improve Red Cell Mass and Neuroprotection in Preterm Infants

NCT03169881 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: NICHD-NRN-0058
• Study Type: interventional
• Target: 650
• Locations: 1 country
• Sites: 16

Brief Summary

Study Hypothesis: Preterm infants administered weekly Darbe during the neonatal period will have improved neurocognitive outcome at 22-26 months compared to placebo

Conditions

Neurocognitive; Neuroprotective; Neonatal; Neurodevelopmental Impairment

Outcome Measures

Primary Outcomes (1)

• Bayley III Composite Cognitive Score

  Bayley Scale of Infant and Toddler Development (BSID)-III composite cognitive score, where subjects who died prior to the follow-up assessment are assigned the lowest possible score of 54. This is a standardized scale where a score that is more than 1 normative standard deviation from the normative mean of 100 signifies mild developmental delay (score \< 85); 2 standard deviations below the mean, moderate delay (score \< 70); and 3 standard deviations below the mean, severe delay (score \< 55). This self-standing scale comprises the primary outcome for the Darbe study.

  22-26 months corrected age (a median of 25 months corrected age, which corresponds to a median of 29 months calendar age in the analysis population), unless the subject died earlier

Secondary Outcomes (13)

• Number of Transfusions Per Infant

  Birth, up to the earliest of: death, hospital discharge, or 35 completed weeks gestational age (a median of 9 weeks)

• Total Volume of Transfusions Per Infant

  Birth, up to the earliest of: death, hospital discharge, or 35 completed weeks gestational age (a median of 9 weeks)

• Number of Donor Exposures Per Infant

  Birth, up to the earliest of: death, hospital discharge, or 35 completed weeks gestational age (a median of 9 weeks)

• Hematocrit

  at 2 and at 7 weeks in the study

• Red Cell Mass

  at 2 and at 7 weeks in the study

Study Arms (2)

Darbepoetin

EXPERIMENTAL

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

Drug: Darbepoetin

Placebo

PLACEBO COMPARATOR

Equal volume normal saline for IV administration, or sham dosing

Drug: Placebo

Interventions

Darbepoetin DRUG

Darbepoetin 10 micrograms/kg/once every week (IV or SC). Infants will be treated until 35 completed weeks gestation, discharge, or transfer to another hospital.

Also known as: Darbe

Darbepoetin

Placebo DRUG

normal saline for IV administration, or sham dosing. Infants will be treated until 35 completed weeks gestation, discharge, or transfer to another hospital.

Also known as: normal saline for IV administration, or sham dosing

Placebo

Eligibility Criteria

• Age: 1 Hour - 24 Hours
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Inborn and outborn preterm infants
• /7-28 6/7 weeks gestational age
• ≤24 hours postnatal age

You may not qualify if:

• Hematocrit \> 60%
• Infants with known congenital or chromosomal anomalies, including congenital heart disease and known brain anomalies
• Hemorrhagic or hemolytic disease
• EEG- confirmed seizures
• Congenital thrombotic disease
• Systolic blood pressures \>100 mm Hg while not on pressor support
• Receiving Epo or Darbe clinically, or planning to receive Epo or Darbe during hospitalization
• Infants in whom no aggressive therapy is planned
• Family will NOT be available for follow-up at 22-26 months

Sponsors & Collaborators

• NICHD Neonatal Research Network: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (16)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

Stanford University

Palo Alto, California, 94304, United States

Location

Emory University

Atlanta, Georgia, 30303, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

University of New Mexico

Albuquerque, New Mexico, 87131, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

RTI International

Durham, North Carolina, 27705, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

Cincinnati Children's Medical Center

Cincinnati, Ohio, 45267, United States

Location

Case Western Reserve University, Rainbow Babies and Children's Hospital

Cleveland, Ohio, 44106, United States

Location

Research Institute at Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Univeristy of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Brown University - Women and Infants Hospital of Rhode Island

Providence, Rhode Island, 02905, United States

Location

University of Texas Southwestern Medical Center at Dallas

Dallas, Texas, 75235, United States

Location

University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

Location

University of Utah

Salt Lake City, Utah, 84108, United States

Location

Related Publications (4)

• Maxwell JR, Ohls RK, An G, Winter D, Beauman S, Buhrman J, Jantzie LL. Development of an electrochemiluminescence assay to measure serum darbepoetin concentration in extremely preterm infants. Bioanalysis. 2025 Dec 14:1-7. doi: 10.1080/17576180.2025.2600914. Online ahead of print.

  PMID: 41392547 DERIVED

• Ohls RK, Das A, Tan S, Lowe JR, Schibler K, Beauman SS, Bell EF, Laptook AR, Baserga M, Patel RM, Carlton DP, Flibotte J, Grisby C, Higgins RD, Shankaran S, Watterberg K, Hibbs AM, Carlo WA, Colaizy TT, Van Meurs KP, Kicklighter SD, Moore R, Sollinger C, Chalak LF, Ghavam S, Poindexter BB, Tyson JE, Cotten CM, Baack ML, Fathi O, DeMauro SB, Laughon MM, Reynolds AM, Duncan AF, Winter S, Wilson-Costello DE, Peralta-Carcelen M, Vohr BR, Harmon HM, Hintz SR, Cavanaugh B, Heyne RJ, Merhar S, Mosquera R, Sewell E, Malcolm WF, Richards LA, Benninger KL, Trembath A; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Darbepoetin, Red Cell Mass, and Neuroprotection in Preterm Infants: A Randomized Clinical Trial. JAMA Pediatr. 2025 Aug 1;179(8):836-845. doi: 10.1001/jamapediatrics.2025.0807.

  PMID: 40354084 DERIVED

• Bahr TM, Tan S, Smith E, Beauman SS, Schibler KR, Grisby CA, Lowe JR, Bell EF, Laptook AR, Shankaran S, Carlton DP, Rau C, Baserga MC, Flibotte J, Zaterka-Baxter K, Walsh MC, Das A, Christensen RD, Ohls RK; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Serum ferritin values in neonates <29 weeks' gestation are highly variable and do not correlate with reticulocyte hemoglobin content. J Perinatol. 2023 Nov;43(11):1368-1373. doi: 10.1038/s41372-023-01751-z. Epub 2023 Aug 18.

  PMID: 37596391 DERIVED

• Vu PT, Ohls RK, Mayock DE, German KR, Comstock BA, Heagerty PJ, Juul SE; PENUT Consortium. Transfusions and neurodevelopmental outcomes in extremely low gestation neonates enrolled in the PENUT Trial: a randomized clinical trial. Pediatr Res. 2021 Jul;90(1):109-116. doi: 10.1038/s41390-020-01273-w. Epub 2021 Jan 11.

  PMID: 33432157 DERIVED

MeSH Terms

Interventions

Darbepoetin alfa; Saline Solution; Organization and Administration

Intervention Hierarchy (Ancestors)

Erythropoietin; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Proteins; Amino Acids, Peptides, and Proteins; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations; Health Services Administration

Results Point of Contact

• Title: Robin K Ohls, MD
• Organization: University of Utah

robin.ohls@hsc.utah.edu

801-581-7052

Study Officials

• Robin Ohls, MD

  University of Utah

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Primary providers and bedside caregivers will be blinded to randomization group. If the dose will be administered IV, the study drug will be administered slow IV push by the bedside nurse. If the dose will be administered subcutaneously, the study drug will be brought to the bedside in a closed container, and injections will be shielded behind screens and out of earshot from caregivers and parents. An adhesive bandage (or 2x2 gauze) will be placed over the true and sham injection sites and either taped or held in place until no evidence of the injection is visible. The parents, medical providers, data collection staff and neurodevelopmental follow up personnel will be masked to the treatment arm.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Model Details: Randomized, masked, placebo-controlled trial

Study Record Dates

• First Submitted: May 24, 2017
• First Posted: May 30, 2017
• Study Start: September 20, 2017
• Primary Completion: December 23, 2022
• Study Completion: May 12, 2025
• Last Updated: November 17, 2025
• Results First Posted: October 30, 2024

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share

Locations

US (16)