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

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ClinicalTrials.gov Identifier: NCT03169881
Recruitment Status : Recruiting
First Posted : May 30, 2017
Last Update Posted : October 8, 2018
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
NICHD Neonatal Research Network

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

Condition or disease Intervention/treatment Phase
Neurocognitive Neuroprotective Neonatal Neurodevelopmental Impairment Drug: Darbepoetin Drug: Placebo Phase 3

Detailed Description:

Advances in neonatal care have led to significant improvements in the survival of the nearly 60,000 very low birth weight (VLBW) infants born each year in the U.S. Improving neurodevelopmental outcomes for these preterm infants continues to be a major goal for neonatal care providers. A subset of these infants sustain a grade 3 or 4 intraventricular hemorrhage (IVH) resulting in an increase in the incidence of developmental delay. Moreover, almost one third of preterm infants with normal head ultrasounds also develop cognitive delay. Although a variety of neuroprotective treatment strategies have been evaluated, no specific treatment has been identified to reduce or prevent brain injury in these most vulnerable preterm infants.

A potential neuroprotective therapy involves administering erythropoiesis stimulating agents (ESAs) such as erythropoietin (Epo) and Darbepoetin (Darbe, a longer acting ESA). In addition to stimulating erythropoiesis, ESAs have been shown to be protective in the developing brain in animal models, making it possibly beneficial for very premature infants who are at risk for intraventricular hemorrhage, hypoxic-ischemic injury, and developmental delay. The neuroprotective mechanisms of ESAs include increased neurogenesis, decreased neuronal susceptibility to glutamate toxicity, decreased neuronal apoptosis, decreased inflammation, decreased nitric oxide-mediated injury, increased antioxidant response, decreased axonal degeneration, and increased protective effects on glia. This is a randomized, masked, placebo controlled clinical study in which enrolled infants will receive weekly Darbe or placebo (sham) dosing.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 650 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Randomized, masked, placebo-controlled trial
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: 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.
Primary Purpose: Treatment
Official Title: Darbepoetin Trial to Improve Red Cell Mass and Neuroprotection in Preterm Infants
Actual Study Start Date : September 20, 2017
Estimated Primary Completion Date : September 2022
Estimated Study Completion Date : September 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Darbepoetin
Darbepoetin 10 micrograms/kg/once every week (IV or SC)
Drug: Darbepoetin
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.
Other Name: Darbe

Placebo Comparator: Placebo
Equal volume normal saline for IV administration, or sham dosing
Drug: Placebo
normal saline for IV administration, or sham dosing. Infants will be treated until 35 completed weeks gestation, discharge, or transfer to another hospital.
Other Name: normal saline for IV administration, or sham dosing




Primary Outcome Measures :
  1. Composite cognitive score on Bayley Scale of Infant Development III [ Time Frame: Birth to 26 months corrected age ]
    The primary outcome is the Bayley III cognitive score. Deaths will be assigned a score of 54.


Secondary Outcome Measures :
  1. Death [ Time Frame: Birth to 26 months corrected age ]
    Death includes any mortality prior to follow-up at 22-26 months of age

  2. Cerebral Palsy [ Time Frame: Follow-up at 26 months corrected age ]
  3. Length of Hospital Stay [ Time Frame: Birth to 26 months corrected age ]
    Days in hospital following birth.

  4. Number of transfusions [ Time Frame: Birth to 35 completed weeks gestational age ]
  5. Hematocrit [ Time Frame: Birth to 35 completed weeks gestational age ]
  6. Red cell mass [ Time Frame: Birth to 35 completed weeks gestational age ]
  7. Volume of transfusions [ Time Frame: Birth to 35 completed weeks gestational age ]
  8. Neurodevelopmental impairment (NDI) [ Time Frame: 26 months corrected age ]
    Severe NDI will be defined by any of the following: a BSID III cognitive score < 70, Gross Motor Functional (GMF) Level of 3-5, blindness (<20/200 vision) or profound hearing loss (inability to understand commands despite amplification); moderate NDI will be defined as a BSID III cognitive score 70-84 and either a GMF level of 2 or a hearing deficit requiring amplification to understand commands or unilateral blindness; mild NDI will be defined by a cognitive score 70-84, or a cognitive score ≥ 85 and any of the following: presence of a GMF level 1 or hearing loss not requiring amplification. Normal (no NDI) will be defined by a cognitive score ≥ 85 and absence of any neurosensory deficits.

  9. Seizures [ Time Frame: Up to 120 days of life ]
    Documented seizures during hospital course

  10. Thromboses [ Time Frame: Up to 120 days of life ]
    Documented thromboses during hospital course

  11. Hypertension [ Time Frame: Up to 120 days of life ]
    Documented hypertension during hospital course

  12. Intra-cranial Hemorrhage (ICH) [ Time Frame: Up to 120 days of life ]
    Documented ICH during hospital course

  13. Necrotizing Enterocolitis (NEC) requiring surgery [ Time Frame: Up to 120 days of life ]
    Documented NEC requiring surgery during hospital course

  14. Bronchopulmonary dysplasia (BPD) [ Time Frame: Up to 120 days of life ]
    Documented BPD during hospital course

  15. Retinopathy of prematurity (ROP) requiring intervention [ Time Frame: Up to 120 days of life ]
    Documented ROP requiring intervention (to include but not limited to laser, cryotherapy, scleral buckle, vitrectomy, avastin Injection) during hospital course

  16. Culture positive sepsis [ Time Frame: Up to 120 days of life ]
    Documented culture positive sepsis during hospital course



Information from the National Library of Medicine

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Ages Eligible for Study:   23 Weeks to 28 Weeks   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Inborn and outborn preterm infants
  • 23 0/7-28 6/7 weeks gestation
  • ≤24 hours postnatal age

Exclusion Criteria:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03169881


Contacts
Contact: Robin Ohls, MD 505-272-0180 rohls@salud.unm.edu
Contact: Rosemary D Higgins, MD 301-435-5575

Locations
United States, Alabama
University of Alabama at Birmingham Recruiting
Birmingham, Alabama, United States, 35233
Contact: Waldemar A. Carlo, MD         
Principal Investigator: Waldemar A. Carlo, MD         
United States, California
Stanford University Recruiting
Palo Alto, California, United States, 94304
Contact: Krisa P. Van Meurs, MD         
Principal Investigator: Krisa P. Van Meurs, MD         
United States, Georgia
Emory University Recruiting
Atlanta, Georgia, United States, 30303
Contact: David Carlton, MD         
United States, Iowa
University of Iowa Recruiting
Iowa City, Iowa, United States, 52242
Contact: Edward F. Bell, MD         
Principal Investigator: Edward F. Bell, MD         
United States, New Mexico
University of New Mexico Recruiting
Albuquerque, New Mexico, United States, 87131
Contact: Robin Ohls, MD    505-272-0180      
Principal Investigator: Kristi L. Watterberg, MD         
United States, New York
University of Rochester Recruiting
Rochester, New York, United States, 14642
Contact: Carl T D'Angio, MD         
Principal Investigator: Carl T D'Angio, MD         
United States, North Carolina
RTI International Active, not recruiting
Durham, North Carolina, United States, 27705
Duke University Recruiting
Durham, North Carolina, United States, 27710
Contact: C. Michael Cotten, MD         
Principal Investigator: C. Michael Cotten, MD         
United States, Ohio
Cincinnati Children's Medical Center Recruiting
Cincinnati, Ohio, United States, 45267
Contact: Brenda Poindiexter, MD         
Principal Investigator: Brenda Poindexter, MD         
Case Western Reserve University, Rainbow Babies and Children's Hospital Recruiting
Cleveland, Ohio, United States, 44106
Contact: Michele C. Walsh, MD MS         
Principal Investigator: Michele C. Walsh, MD MS         
Research Institute at Nationwide Children's Hospital Recruiting
Columbus, Ohio, United States, 43205
Contact: Pablo Sanchez, MD         
Principal Investigator: Pablo Sanchez, MD         
United States, Pennsylvania
Univeristy of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Eric C Eichenwald, MD         
Principal Investigator: Eric C Eichenwald, MD         
United States, Rhode Island
Brown University - Women and Infants Hospital of Rhode Island Recruiting
Providence, Rhode Island, United States, 02905
Contact: Abbot R. Laptook, MD         
Principal Investigator: Abbot R Laptook, MD         
United States, Texas
University of Texas Southwestern Medical Center at Dallas Not yet recruiting
Dallas, Texas, United States, 75235
Contact: Myra Myckoff, MD         
Principal Investigator: Myra Wyckoff, MD         
University of Texas Health Science Center at Houston Not yet recruiting
Houston, Texas, United States, 77030
Contact: Jon Tyson         
Principal Investigator: Jon Tyson, MD, MPH         
United States, Utah
University of Utah Recruiting
Salt Lake City, Utah, United States, 84108
Contact: Bradley Yoder, MD         
Principal Investigator: Bradley Yoder, MD         
Sponsors and Collaborators
NICHD Neonatal Research Network
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
Principal Investigator: Robin Ohls, MD University of Mexico

Responsible Party: NICHD Neonatal Research Network
ClinicalTrials.gov Identifier: NCT03169881     History of Changes
Other Study ID Numbers: NICHD-NRN-0058
First Posted: May 30, 2017    Key Record Dates
Last Update Posted: October 8, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: NIH has had a long-standing policy to share and make available to the public the results and accomplishments of the activities that it funds. The NRN plans to share de-identified data after final publication in an NIH supported data repository such as the NICHD Data and Specimen Hub (https://dash.nichd.nih.gov) or NHLBI BIOLINCC (https://biolincc.nhlbi.nih.gov/home/).

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Darbepoetin alfa
Hematinics