Hypoxic Ischemic EncephalopathyPhase 1/2DANCENCT01471015
Darbe Administration in Newborns Undergoing Cooling for Encephalopathy
A Phase 1/2 study testing Darbepoetin alfa in people with Hypoxic Ischemic Encephalopathy, run by University of Utah at 7 sites in United States.
Trial summary
Selective head cooling or whole body hypothermia has become the standard of care for neonatal hypoxia-ischemia encephalopathy (HIE). Despite early intervention death or major neurodevelopmental disability still occurs in nearly 50% of infants ≥ 36 weeks gestational age (GA) treated with cooling. Read more about this study
- Who is it for?
- Ages Up to 24 hours
- Conditions the study is for
- Hypoxic Ischemic Encephalopathy
- What is being tested?
- Darbepoetin alfa
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 7 sitesUnited States
- Study dates
- Sep 2012to Jan 2014
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 24 hours
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Infants will be eligible for the DANCE trial if they have a gestational age > 36 weeks by best obstetric estimate, are < 12 hours old and have evidence of moderate-severe acute perinatal HIE. Eligibility will also include criteria presently used in the NICU to initiate hypothermia:
- < 6 hours after birth
- History of an acute perinatal event (abruption, cord prolapsed, severe fetal heart rate abnormality)
- Severe fetal or early (< 1 hour age) neonatal acidosis: arterial pH ≤ 7.0 or a base deficit ≥ 16m mEq/ L
- If a blood gas is not available or a blood gas at <1 hour of age has a pH between 7.01 and 7.15, or a base deficit is between 10 and 15.9 mEq/L, additional criteria will be required:
- acute perinatal event AND
- either a 10-min Apgar score ≤ 5 or assisted ventilation initiated at birth and continued for at least 10 minutes.
Who cannot join
- Major congenital and/or chromosomal abnormalities
- Prenatal diagnosis of brain abnormality or hydrocephalus
- Severe growth restriction (< 1800g)
- Central venous hematocrit > 65%, platelet count > 600,000/dL, and/or neutropenia (ANC < 500 µL)
- Maternal history of major vascular thrombosis or multiple fetal losses (> 3 spontaneous abortions)
- ECMO
- Infant judged critically ill and unlikely to benefit from neonatal intensive care by the attending neonatologist
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
University of New Mexico
Albuquerque, New Mexico, 87131-0001
Vanderbilt University School of Medicine
Nashville, Tennessee, 37232-9544
McKay Dee Hospital- Intermountain Healthcare
Ogden, Utah, 84403
University of Utah
Salt Lake City, Utah, 84108
Primary Children's Hospital
Salt Lake City, Utah, 84132
Intermountain Medical Center
Sandy City, Utah, 841074
University of Washington
Seattle, Washington, 98195-6320
About this study
Selective head cooling or whole body hypothermia has become the standard of care for neonatal hypoxia-ischemia encephalopathy (HIE). Despite early intervention death or major neurodevelopmental disability still occurs in nearly 50% of infants ≥ 36 weeks gestational age (GA) treated with cooling. No additional therapies have proven to be efficacious in further reducing brain injury and impairment for these high risk infants. Neuroprotective strategies aimed at improving early childhood outcomes are still needed. An important area of study includes therapies that may complement the neuroprotective effects of hypothermia and promote neuronal regeneration, recovery and neurovascular remodeling. Among these therapies, erythropoiesis stimulating agents (ESA) have been shown to provide neuroprotection, improving short and long-term neurologic outcome in brain injury and HIE in neonatal and adult animal models. Parallel with neuroprotective effects in experimental settings, recent small clinical studies suggest improved outcomes after ESA administration in patients with severe traumatic brain injury and HIE. ESA may work through several important mechanisms including reduced inflammation, limited oxidative stress, decreased apoptosis and white matter injury, as well as via pro-angiogenic and neurogenic properties.
Darbepoetin alfa (Darbe), a recombinant human erythropoietin (EPO)-derived molecule, has an extended circulating half life and comparable biological activity to EPO, including activation of the EPO receptor. The proposed study is a Phase I/II dose safety and pharmacokinetic trial of early Darbe administered concurrent with hypothermia in human newborn infants with moderate to severe birth asphyxia. The long-term objectives of the proposed research are to reduce mortality and to decrease the risk of long-term disabilities in infants with HIE who survive beyond the newborn period.
- Conditions
- Hypoxic Ischemic Encephalopathy
- Being tested
- Darbepoetin alfa, Placebo
- Keywords
- Hypoxic Ischemic Encephalopathy, Cooling Therapy, HIE
- Medical subject headings
- Hypoxia-Ischemia, Brain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Darbepoetin alfaDrug
10 mcg/kg/dose x2, with the first dose given as IV within 12 hours of delivery and the second dose given as IV or SQ at 7 days old.
Darbepoetin alfaDrug
2 mcg/kg/dose x2, with the first dose given IV within 12 hours of delivery and the second dose given IV or SQ at 7 days old.
PlaceboDrug
Placebo given x2, with the first dose given IV within 12 hours of delivery and the second dose given IV or SQ at 7 days old
| Study group | Role | What they receive |
|---|---|---|
| High dose Darbepoetin alfa | Active comparator | 10 mcg/kg/dose Darbe x2 doses, with the first dose within 12 hours of delivery and the second dose at 7 days Receives: Drug: Darbepoetin alfa |
| Low dose Darbepoetin alfa | Active comparator | 2 mcg/kg/dose Darbe x2, with the first dose given within 12 hours of delivery and the second dose given at 7 days old. Receives: Drug: Darbepoetin alfa |
| Placebo | Placebo comparator | Placebo given x2 doses, with the first given within 12 hours of delivery and the second given at 7 days old Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Pharmacokinetic Profile of Darbe After the First Dose During Cooling
The pharmacokinetic profile of Darbe wil be determined using "population" pharmacokinetic sampling in which babies will be randomized to have blood drawn at different intervals. Serum levels will be drawn at 4,12, 18, 24, 36, 60, and 72 hours post initial dose. Area under the plasma concentration versus time curve (AUC) will be used.
Measured: For 72 hours after first dose
The Pharmacokinetic Profile of Darbe After the Second Dose.
The pharmacokinetic profile of Darbe will be determined using "population" pharmacokinetic sampling in which babies will be randomized to have blood drawn at different intervals. A second dose of Darbe will be given at 7 days of age, and serum drug levels will be obtained at 12, 18, 24, and 36 hours post second dose. Area under the plasma concentration versus time curve (AUC) will be used.
Measured: For 36 hours after second dose
Secondary outcomes (1)
Number of Participants With Adverse Events.
Potential adverse events such as (but not limited to) alterations in blood pressure, secondary infections, neutropenia, thrombotic/vascular events, hematologic events (platelets, Hct level, polycythemia), and hepatic/renal function that are outside of normal range for the study population.
Complications associated with HIE or cooling therapy will not be considered an AE for this study. AEs reported to be associated with cooling include: bleeding/thrombosis, persistent pulmonary hypertension of the newborn (PPHN), skin changes, arrhythmia, and persistent acidosis.
Measured: 30 days or until hospital discharge
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Nov 2011 (estimated)
- Study startSep 2012
- Primary completionJan 2014
- Study completionJan 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Hypoxic Ischemic EncephalopathyStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Utah
- Sponsor type
- University, hospital or other
- Collaborators
- Thrasher Research Fund
- Responsible party
- Principal investigator, Mariana Baserga, University of Utah
- Investigators
- Mariana Baserga, MD, Principal investigator, University of Utah
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01471015
- Sponsor's protocol ID
- 49096
- Acronym
- DANCE
- Status last verified
- Jul 2024
- First submitted
- 2 Nov 2011
- Last updated
- 23 Jul 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 23 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Darbe Administration in Newborns Undergoing Cooling for Encephalopathy
- ClinicalTrials.gov ID
- NCT01471015
- Acronym / sponsor ID
- DANCE / 49096
- Conditions
- Hypoxic Ischemic Encephalopathy
- Keywords
- Hypoxic Ischemic Encephalopathy, Cooling Therapy, HIE
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- University of UtahUniversity, hospital or other
- Collaborators
- Thrasher Research Fund
- Study start
- Sep 2012
- Primary completion
- Jan 2014 (actual)
- Study completion
- Jan 2014 (actual)
- First posted
- 11 Nov 2011 (estimated)
- Results
- Posted 22 May 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Selective head cooling or whole body hypothermia has become the standard of care for neonatal hypoxia-ischemia encephalopathy (HIE). Despite early intervention death or major neurodevelopmental disability still occurs in nearly 50% of infants ≥ 36 weeks gestational age (GA) treated with cooling. No additional therapies have proven to be efficacious in further reducing brain injury and impairment for these high risk infants. Neuroprotective strategies aimed at improving early childhood outcomes are still needed. An important area of study includes therapies that may complement the neuroprotective effects of hypothermia and promote neuronal regeneration, recovery and neurovascular remodeling. Among these therapies, erythropoiesis stimulating agents (ESA) have been shown to provide neuroprotection, improving short and long-term neurologic outcome in brain injury and HIE in neonatal and adult animal models. Parallel with neuroprotective effects in experimental settings, recent small clinical studies suggest improved outcomes after ESA administration in patients with severe traumatic brain injury and HIE. ESA may work through several important mechanisms including reduced inflammation, limited oxidative stress, decreased apoptosis and white matter injury, as well as via pro-angiogenic and neurogenic properties.
Darbepoetin alfa (Darbe), a recombinant human erythropoietin (EPO)-derived molecule, has an extended circulating half life and comparable biological activity to EPO, including activation of the EPO receptor. The proposed study is a Phase I/II dose safety and pharmacokinetic trial of early Darbe administered concurrent with hypothermia in human newborn infants with moderate to severe birth asphyxia. The long-term objectives of the proposed research are to reduce mortality and to decrease the risk of long-term disabilities in infants with HIE who survive beyond the newborn period.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| High dose Darbepoetin alfa | Active comparator | Drug: Darbepoetin alfa10 mcg/kg/dose Darbe x2 doses, with the first dose within 12 hours of delivery and the second dose at 7 days |
| Low dose Darbepoetin alfa | Active comparator | Drug: Darbepoetin alfa2 mcg/kg/dose Darbe x2, with the first dose given within 12 hours of delivery and the second dose given at 7 days old. |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo given x2 doses, with the first given within 12 hours of delivery and the second given at 7 days old |
Who may qualify
- Ages
- Up to 24 hours
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (7 listed)
- Infants will be eligible for the DANCE trial if they have a gestational age > 36 weeks by best obstetric estimate, are < 12 hours old and have evidence of moderate-severe acute perinatal HIE. Eligibility will also include criteria presently used in the NICU to initiate hypothermia:
- < 6 hours after birth
- History of an acute perinatal event (abruption, cord prolapsed, severe fetal heart rate abnormality)
- Severe fetal or early (< 1 hour age) neonatal acidosis: arterial pH ≤ 7.0 or a base deficit ≥ 16m mEq/ L
- If a blood gas is not available or a blood gas at <1 hour of age has a pH between 7.01 and 7.15, or a base deficit is between 10 and 15.9 mEq/L, additional criteria will be required:
Key exclusion criteria (7 listed)
- Major congenital and/or chromosomal abnormalities
- Prenatal diagnosis of brain abnormality or hydrocephalus
- Severe growth restriction (< 1800g)
- Central venous hematocrit > 65%, platelet count > 600,000/dL, and/or neutropenia (ANC < 500 µL)
- Maternal history of major vascular thrombosis or multiple fetal losses (> 3 spontaneous abortions)
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 alfa10 mcg/kg/dose x2, with the first dose given as IV within 12 hours of delivery and the second dose given as IV or SQ at 7 days old. | Drug | High dose Darbepoetin alfa |
| Darbepoetin alfa2 mcg/kg/dose x2, with the first dose given IV within 12 hours of delivery and the second dose given IV or SQ at 7 days old. | Drug | Low dose Darbepoetin alfa |
| PlaceboPlacebo given x2, with the first dose given IV within 12 hours of delivery and the second dose given IV or SQ at 7 days old | Drug | Placebo |
Primary outcome
The Pharmacokinetic Profile of Darbe After the First Dose During Cooling
Time frame: For 72 hours after first dose
The pharmacokinetic profile of Darbe wil be determined using "population" pharmacokinetic sampling in which babies will be randomized to have blood drawn at different intervals. Serum levels will be drawn at 4,12, 18, 24, 36, 60, and 72 hours post initial dose. Area under the plasma concentration versus time curve (AUC) will be used.
The Pharmacokinetic Profile of Darbe After the Second Dose.
Time frame: For 36 hours after second dose
The pharmacokinetic profile of Darbe will be determined using "population" pharmacokinetic sampling in which babies will be randomized to have blood drawn at different intervals. A second dose of Darbe will be given at 7 days of age, and serum drug levels will be obtained at 12, 18, 24, and 36 hours post second dose. Area under the plasma concentration versus time curve (AUC) will be used.
1 secondary outcome
Number of Participants With Adverse Events.
Time frame: 30 days or until hospital discharge
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jul 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Hypoxic Ischemic Encephalopathy
Not yet recruiting
Levetiracetam as an Adjuvant Therapy to Hypothermia in Neonatal Asphyxia
Hypoxic Ischemic Encephalopathy of Newborn, Neuro-protection
RecruitingPhase 2
The PROTECT-HIE Pilot Trial
Hypoxic-ischemic Encephalopathy (HIE)
RecruitingPhase 2
A Dose Escalation Study of Levetiracetam in the Treatment of Neonatal Seizures
Neonatal Seizure, Neonatal Encephalopathy
RecruitingObservational study
Continuous Monitoring of Body Temperature in Neonates During Therapeutic Hypothermia
Therapeutic Hypothermia, Neonatal Hypoxic-Ischemic Encephalopathy
Not yet recruitingObservational study
Newborn Brain Assessment - CergenX Wave
Neonatal Encephalopathy, Neonatal Encephalopathy (Neonatal Hypoxic-ischemic Encephalopathy)
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.
Mariana Baserga, MD principal investigator
University of Utah
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Darbepoetin alfa in people with Hypoxic Ischemic Encephalopathy, run by University of Utah at 7 sites in United States.
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 7 inclusion and 7 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: finished, as of the sponsor's last update on 23 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States. 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. Some participants in this study may receive a placebo. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 May 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The Pharmacokinetic Profile of Darbe After the First Dose During Cooling (time frame: For 72 hours after first dose). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 23 Jul 2024; AzTrials last refreshed its copy on 31 Oct 2026.