Iron-deficiencyPhase 3NCT04691843
Iron Supplementation and Neurodevelopmental Outcome in ELGANs
A Phase 3 study testing Iron Sulfate in people with Iron-deficiency, run by Ann & Robert H Lurie Children's Hospital of Chicago at 1 site in United States.
Trial summary
This study explores the relationship between iron deficiency and neurological outcome of extremely premature infants. Premature birth occurs during a critical period of brain development and maturation, and before adequate transfer of iron across the placenta. Read more about this study
- Who is it for?
- Ages 7 days to 4 weeks
- Conditions the study is for
- Iron-deficiency
- What is being tested?
- Iron Sulfate
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 51 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Feb 2021to 31 Aug 2024
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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 7 days to 4 weeks
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- NICU inpatients between 24-0/7 and 30-6/7 weeks of gestation
- Infants older than one week of age and tolerating at least 60ml/kg/day of enteral feeds.
- Parental permission obtained prior to start of study
Who cannot join
- In extremis during consent window (as judged by primary attending provider)
- Known or suspected genetic disorder
- Unable to return for follow-up evaluation at 2 years of age
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Role of Iron Supplementation in Neurodevelopmental Outcome of Extremely Preterm Infants - A Pilot Study
This study explores the relationship between iron deficiency and neurological outcome of extremely premature infants. Premature birth occurs during a critical period of brain development and maturation, and before adequate transfer of iron across the placenta. Nutrition has a significant impact on ultimate outcome of survivors of prematurity. One of the biomarkers of nutrition in the premature infant is iron, and iron supplementation is essential for growth and brain development at low gestational age. As a result, the Committee on Nutrition of the American Academy of Pediatrics (AAP) recommends daily oral iron supplementation, of at least 2-4 mg/kg/day from 2 weeks of age, to prevent iron deficiency in extremely premature infants. Nevertheless, studies have shown that even with this regular care dose of iron, started from 2 weeks of age, a significant number of premature infants will still develop iron-deficiency. Our hypothesis states that starting high dose iron supplementation early will improve neurological development and outcome in extremely premature infants (those born at less than 28 weeks gestational age). This study will provide data showing whether individualized iron supplementation using higher doses of iron, started earlier (after the first week of life) when guided by periodic screening of their body's iron status with ferritin levels, will mitigate iron deficiency and promote improved neurodevelopmental outcome in this vulnerable infant population.
Read the detailed description
This is a prospective, randomized, unblinded, controlled study of early, high-dose iron for neuroprotection in extremely preterm infants born between 24 0/7 weeks and 30 6/7 weeks gestation. This study has chosen to study newborns between 24-0/7 and 30-6/7 weeks of gestation because of (1) high likelihood of poor outcome, (2) highest risk of iron deficiency and potentially most likely to benefit from intervention based on their stage of brain development, (3) previously studied to assess safety of this iron regimen in Preterm Erythropoietin Neuroprotection Trial (PENUT) protocol, and (4) absence of therapeutic interventions to improve neurodevelopmental outcome. Study sample size is 90 patients; to be enrolled at Ann \& Robert H Lurie Children's Hospital-Prentice Women's Hospital. We expect to evaluate 82 infants at 10-14 months and 22-26 months corrected age, our primary endpoints. There is no enrollment restriction based on race, ethnicity or gender. Enrollment is expected to take 18-24 months, with each subject with each subject participating through 24-26 months corrected age when final neurodevelopmental outcomes are assessed. Subjects will be randomized locally to regular-dose iron as recommended by AAP or early, high-dose iron. High-dose iron will continue until 36 weeks corrected age. Serial measurements of hemoglobin, reticulocyte count, reticulocyte hemoglobin equivalent and ferritin levels will be obtained, starting 2 weeks after starting iron supplementation, with final measurement obtained at 40 weeks corrected age or prior to discharge, whichever is first. Data will be abstracted regarding interval medical history from the electronic medical record. After discharge, Neonatal Intensive Care Unit (NICU) developmental follow-up will occur at 12 months and 24 months corrected age, at which time standardized neurodevelopmental assessments will be performed. The outcome measure is neurodevelopmental outcome at 10-14 months and 22-26 months of age. Our estimated sample size is based on the assumption that early high dose iron supplementation will reduce abnormal neurological outcome by 16%-29%, and taken together with an estimated 10% anticipated loss due to unrelated deaths, the total sample size was calculated at 90 infants (45 in each arm of the study).
- Conditions
- Iron-deficiency
- Being tested
- Iron Sulfate
- Keywords
- extreme prematurity, neurodevelopmental impairment, ferritin
- Medical subject headings
- Anemia, Iron-Deficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Iron SulfateDrug
Also called Ferrous Sulfate
Early, high dose, iron supplementation
| Study group | Role | What they receive |
|---|---|---|
| Standard iron dose | Active comparator | Iron supplementation of 4mg/kg/day will start when infant is on full enteral feedings of 120-150mL/kg/day and at least two weeks old. Iron dosing will be adjusted for weight at weekly intervals to maintain dosing at 4mg/kg/day. Receives: Drug: Iron Sulfate |
| Early, high-dose iron | Experimental | Iron supplementation will start at 3mg/kg/day when infant is on enteral feeds of 60mL/kg/day and at least one week old, then increased to 6mg/kg/day when enteral feeds are at 100mL/kg/day. Iron dosing will be adjusted to maintain ferritin level of 70-400ng/mL. At 36 weeks corrected age, iron supplementation will be adjusted to the dose routinely used for preterm infants. Receives: Drug: Iron Sulfate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Neurodevelopmental outcome in participants
ND impairment (NDI): defined as the presence of any of the following: Bayley Scales of Development III Motor Standard Score, Language or Cognitive Standard Score < 70 (severe, 2 standard deviations (SD) below mean) or < 85 (moderate, 1 SD below mean)
Measured: 22-26 months corrected age
Secondary outcomes (4)
Iron insufficiency as assessed by ferritin level (ng/mL)
Iron insufficiency will be determined by ferritin level less than 70 ng/mL
Measured: At discharge or 40 weeks corrected age (whichever occurs first), up to 16 weeks
Iron insufficiency as assessed by hemoglobin level (g/dL)
Iron insufficiency will be determined by hemoglobin level less than 8 g/dL
Measured: At discharge or 40 weeks corrected age (whichever occurs first), up to 16 weeks
Iron insufficiency as assessed by reticulocyte hemoglobin equivalent (Ret-He, pg)
Iron insufficiency will be determined by Ret-He less than 27.2 pg
Measured: At discharge or 40 weeks corrected age (whichever occurs first), up to 16 weeks
Iron insufficiency as assessed by reticulocyte count (%)
Iron insufficiency will be determined by reticulocyte count less than 2%
Measured: At discharge or 40 weeks corrected age (whichever occurs first), up to 16 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Dec 2020
- Study start1 Feb 2021
- Primary completion31 Aug 2024
- Study completion31 Aug 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Iron-deficiencyStudies 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 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 51 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ann & Robert H Lurie Children's Hospital of Chicago
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Janine Yasmin Khan, Ann & Robert H Lurie Children's Hospital of Chicago
- Investigators
- Janine Y Khan, MD, MBA, Principal investigator, Ann & Robert H Lurie Children's Hospital of Chicago
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04691843
- Sponsor's protocol ID
- 2021-4092
- Status last verified
- Nov 2024
- First submitted
- 14 Dec 2020
- Last updated
- 12 Nov 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: There is not a plan to make IDP available.
Study at a glance
From the registry record, last updated by the sponsor on 12 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Role of Iron Supplementation in Neurodevelopmental Outcome of Extremely Preterm Infants - A Pilot Study
- ClinicalTrials.gov ID
- NCT04691843
- Acronym / sponsor ID
- 2021-4092
- Conditions
- Iron-deficiency
- Keywords
- extreme prematurity, neurodevelopmental impairment, ferritin
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 51 participants (actual)
- Lead sponsor
- Ann & Robert H Lurie Children's Hospital of ChicagoUniversity, hospital or other
- Study start
- 1 Feb 2021 (actual)
- Primary completion
- 31 Aug 2024 (actual)
- Study completion
- 31 Aug 2024 (actual)
- First posted
- 31 Dec 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study explores the relationship between iron deficiency and neurological outcome of extremely premature infants. Premature birth occurs during a critical period of brain development and maturation, and before adequate transfer of iron across the placenta. Nutrition has a significant impact on ultimate outcome of survivors of prematurity. One of the biomarkers of nutrition in the premature infant is iron, and iron supplementation is essential for growth and brain development at low gestational age. As a result, the Committee on Nutrition of the American Academy of Pediatrics (AAP) recommends daily oral iron supplementation, of at least 2-4 mg/kg/day from 2 weeks of age, to prevent iron deficiency in extremely premature infants. Nevertheless, studies have shown that even with this regular care dose of iron, started from 2 weeks of age, a significant number of premature infants will still develop iron-deficiency. Our hypothesis states that starting high dose iron supplementation early will improve neurological development and outcome in extremely premature infants (those born at less than 28 weeks gestational age). This study will provide data showing whether individualized iron supplementation using higher doses of iron, started earlier (after the first week of life) when guided by periodic screening of their body's iron status with ferritin levels, will mitigate iron deficiency and promote improved neurodevelopmental outcome in this vulnerable infant population.
Detailed description
This is a prospective, randomized, unblinded, controlled study of early, high-dose iron for neuroprotection in extremely preterm infants born between 24 0/7 weeks and 30 6/7 weeks gestation. This study has chosen to study newborns between 24-0/7 and 30-6/7 weeks of gestation because of (1) high likelihood of poor outcome, (2) highest risk of iron deficiency and potentially most likely to benefit from intervention based on their stage of brain development, (3) previously studied to assess safety of this iron regimen in Preterm Erythropoietin Neuroprotection Trial (PENUT) protocol, and (4) absence of therapeutic interventions to improve neurodevelopmental outcome. Study sample size is 90 patients; to be enrolled at Ann \& Robert H Lurie Children's Hospital-Prentice Women's Hospital. We expect to evaluate 82 infants at 10-14 months and 22-26 months corrected age, our primary endpoints. There is no enrollment restriction based on race, ethnicity or gender. Enrollment is expected to take 18-24 months, with each subject with each subject participating through 24-26 months corrected age when final neurodevelopmental outcomes are assessed. Subjects will be randomized locally to regular-dose iron as recommended by AAP or early, high-dose iron. High-dose iron will continue until 36 weeks corrected age. Serial measurements of hemoglobin, reticulocyte count, reticulocyte hemoglobin equivalent and ferritin levels will be obtained, starting 2 weeks after starting iron supplementation, with final measurement obtained at 40 weeks corrected age or prior to discharge, whichever is first. Data will be abstracted regarding interval medical history from the electronic medical record. After discharge, Neonatal Intensive Care Unit (NICU) developmental follow-up will occur at 12 months and 24 months corrected age, at which time standardized neurodevelopmental assessments will be performed. The outcome measure is neurodevelopmental outcome at 10-14 months and 22-26 months of age. Our estimated sample size is based on the assumption that early high dose iron supplementation will reduce abnormal neurological outcome by 16%-29%, and taken together with an estimated 10% anticipated loss due to unrelated deaths, the total sample size was calculated at 90 infants (45 in each arm of the study).
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard iron dose | Active comparator | Drug: Iron SulfateIron supplementation of 4mg/kg/day will start when infant is on full enteral feedings of 120-150mL/kg/day and at least two weeks old. Iron dosing will be adjusted for weight at weekly intervals to maintain dosing at 4mg/kg/day. |
| Early, high-dose iron | Experimental | Drug: Iron SulfateIron supplementation will start at 3mg/kg/day when infant is on enteral feeds of 60mL/kg/day and at least one week old, then increased to 6mg/kg/day when enteral feeds are at 100mL/kg/day. Iron dosing will be adjusted to maintain ferritin level of 70-400ng/mL. At 36 weeks corrected age, iron supplementation will be adjusted to the dose routinely used for preterm infants. |
Who may qualify
- Ages
- 7 days to 4 weeks
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- NICU inpatients between 24-0/7 and 30-6/7 weeks of gestation
- Infants older than one week of age and tolerating at least 60ml/kg/day of enteral feeds.
- Parental permission obtained prior to start of study
Key exclusion criteria (3 listed)
- In extremis during consent window (as judged by primary attending provider)
- Known or suspected genetic disorder
- Unable to return for follow-up evaluation at 2 years of age
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 |
|---|---|---|
| Iron SulfateAlso: Ferrous SulfateEarly, high dose, iron supplementation | Drug | Early, high-dose iron, Standard iron dose |
Primary outcome
Neurodevelopmental outcome in participants
Time frame: 22-26 months corrected age
ND impairment (NDI): defined as the presence of any of the following: Bayley Scales of Development III Motor Standard Score, Language or Cognitive Standard Score < 70 (severe, 2 standard deviations (SD) below mean) or < 85 (moderate, 1 SD below mean)
4 secondary outcomes
Iron insufficiency as assessed by ferritin level (ng/mL)
Time frame: At discharge or 40 weeks corrected age (whichever occurs first), up to 16 weeks
Iron insufficiency as assessed by hemoglobin level (g/dL)
Time frame: At discharge or 40 weeks corrected age (whichever occurs first), up to 16 weeks
Iron insufficiency as assessed by reticulocyte hemoglobin equivalent (Ret-He, pg)
Time frame: At discharge or 40 weeks corrected age (whichever occurs first), up to 16 weeks
Iron insufficiency as assessed by reticulocyte count (%)
Time frame: At discharge or 40 weeks corrected age (whichever occurs first), up to 16 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Nov 2024.
- Individual participant dataSharing planned: No. There is not a plan to make IDP available.
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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.
Janine Y Khan, MD, MBA principal investigator
Ann & Robert H Lurie Children's Hospital of Chicago
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Iron Sulfate in people with Iron-deficiency, run by Ann & Robert H Lurie Children's Hospital of Chicago at 1 site 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 3 inclusion and 3 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 12 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Neurodevelopmental outcome in participants (time frame: 22-26 months corrected age). 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 12 Nov 2024.