Oral Iron Supplements for Premature Infants

Overseen By Donna Rodney

Age: < 18

Sex: Any

Trial Phase: Academic

Sponsor: CHRISTUS Health

Must be taking: Oral iron

Disqualifiers: Congenital anomalies, Chromosomal abnormalities, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 36 weeks post-menstrual age

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the best method for administering iron supplements to premature babies by comparing daily doses to every-other-day doses. The goal is to determine if both schedules help babies achieve iron sufficiency by a specific time. The trial uses ferrous sulfate, an oral iron supplement. Ideal candidates are premature babies who are currently hospitalized and receiving full feeding through the stomach. This research could enhance care for premature infants needing iron. As an unphased trial, it offers a unique opportunity to contribute to improving treatment strategies for these 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 oral iron supplements are safe for premature infants?

Research has shown that oral iron supplements like ferrous sulfate are generally safe for preterm infants. Studies indicate that long-term use of iron supplements improves iron levels in these infants and reduces the risk of iron deficiency and anemia, a condition where the blood lacks enough healthy red blood cells.

The trial uses an iron dosage based on guidelines proven safe for preterm infants. Researchers will monitor blood levels to ensure iron remains at a safe and balanced level. However, premature infants should not begin iron supplements until their vitamin E levels, which are low at birth, are restored.

Overall, oral iron supplements have been well-tolerated in similar situations when used with proper medical advice and monitoring. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it compares two different dosing schedules of oral iron supplementation, aiming to optimize iron delivery for premature infants. Unlike the standard practice of daily dosing, one group receives iron every other day, which might improve absorption and reduce side effects. By monitoring blood counts and iron levels regularly, researchers hope to find out if the less frequent dosing can maintain adequate iron levels while being gentler on the infants' developing systems. This trial could lead to a new protocol that is both effective and safer for these vulnerable patients.

What evidence suggests that oral iron supplements could be effective for premature infants?

This trial will compare two different dosing schedules of oral iron supplements for premature infants. Studies have shown that iron supplements can significantly improve iron levels and reduce iron deficiency in babies born early. Research indicates that long-term iron intake helps prevent anemia, a condition characterized by a lack of healthy red blood cells. Oral iron, such as ferrous sulfate, effectively treats iron deficiency anemia, though it may cause some stomach discomfort. Previous patients demonstrated improvement in iron levels with similar doses. The treatment aims to help infants reach healthy iron levels without increasing the dosage. ^{1 2 6 7 8}

Who Is on the Research Team?

Pratik K Parikh, MD

Principal Investigator

CHRISTUS Health

Richelle L Homo, MD

Principal Investigator

CHRISTUS Health; Brooke Army Medical Center

Are You a Good Fit for This Trial?

This trial is for premature infants with conditions like very low birth weight and anemia due to iron deficiency. The study aims to include those who need iron supplementation as part of their care.

Inclusion Criteria

I am under 18 years old.

I am a newborn.

I am currently in the hospital.

Exclusion Criteria

My infant has a condition affecting iron levels, like thalassemia or hemochromatosis.

My infant has a known genetic condition like Down syndrome.

My infant has a bleeding disorder.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either daily or every other day oral iron supplementation after achieving full enteral feeds

Up to 36 weeks post-menstrual age

Initial visit followed by bi-weekly monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of iron replete status and other health outcomes

12-24 months

What Are the Treatments Tested in This Trial?

Interventions

• Oral Iron as Ferrous Sulfate

Trial Overview The IQONic trial is testing whether giving premature infants oral iron supplements every day has the same effect on their health as giving the same total weekly dose divided over every other day.

How Is the Trial Designed?

Group I: Intervention Group Experimental Treatment 1 Intervention

After the infant achieves full enteral feeds, the infant is started on 6mg/kg of oral iron supplementation administered every other day. The dose of 6 mg/kg of enteral iron was chosen based on the aforementioned recommendations with evidence of its safety, while minimizing the need to increase the enteral iron dosage if an infant were to be started on ESAs where a dose of 6 mg/kg of enteral iron supplementation is the standard practice. Phlebotomy to obtain a complete blood count, reticulocyte count, and reticulocyte hemoglobin count is pursued the Monday after starting iron supplementation and every 2 weeks thereafter to weeks to monitor hematocrit or hemoglobin levels and iron status.

Group II: Control Group Experimental Treatment 1 Intervention

After the infant achieves full enteral feeds, the infant is started on 6 mg/kg of oral iron daily supplementation. The dose of 6 mg/kg of enteral iron was chosen based on the aforementioned recommendations with evidence of its safety, while minimizing the need to increase the enteral iron dosage if an infant were to be started on ESAs where a dose of 6 mg/kg of enteral iron supplementation is the standard practice. Phlebotomy to obtain a complete blood count, reticulocyte count, and reticulocyte hemoglobin count is pursued the Monday after starting iron supplementation and every 2 weeks thereafter to weeks to monitor hematocrit or hemoglobin levels and iron status.

Oral Iron as Ferrous Sulfate is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Ferrous sulfate for:

• Iron deficiency anemia
• Anemia due to chronic kidney disease
• Vitamin/mineral supplementation and deficiency
• Vitamin/mineral supplementation during pregnancy/lactation

Approved in United States as Ferrous sulfate for:

• Iron deficiency anemia
• Anemia due to chronic kidney disease
• Vitamin/mineral supplementation and deficiency
• Vitamin/mineral supplementation during pregnancy/lactation

Approved in Canada as Ferrous sulfate for:

• Iron deficiency anemia
• Anemia due to chronic kidney disease
• Vitamin/mineral supplementation and deficiency
• Vitamin/mineral supplementation during pregnancy/lactation

Who Is Running the Clinical Trial?

CHRISTUS Health

Lead Sponsor

Trials

16

Recruited

1,900+

Published Research Related to This Trial

In a study analyzing 287 clinical records of young infants, ferrous sulfate was prescribed as a preventive therapy for iron deficiency anemia in 100% of cases, indicating strong adherence to the recommendation for iron supplementation.

However, only 18.1% of the prescriptions met all five criteria for adequacy, with the lowest compliance seen in dosage (29.2%), highlighting the need for improved practices in prescribing iron supplements to ensure effective prevention of anemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the prescription pattern of ferrous sulfate as a therapy for preventing iron deficiency anemia in infants. Vásquez-Guzmán, RA., Solano-Ceh, A., Villarreal-Ríos, E., et al.[2022]

In a study of 13 iron-deficient patients, the absorption of 100 mg ferrous sulfate was found to be comparable to 176 mg of ferrous gluconate, indicating that ferrous sulfate may be an effective option for iron supplementation.

In a larger study of 113 subjects, the reported side effects were notably high for all types of iron tablets tested, suggesting that participant selection and study design may influence side effect reporting, highlighting the need for careful comparison across studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Absorption and side-effects after peroral administration of sustained release iron tablets. Ferro-Retard compared with Ferronicum and Duroferon Duretter. Levy, F., Anderson, P., Ekren, T.[2021]

Ferrous sulfate, a common treatment for iron deficiency anemia, can cause mucosal damage in the upper gastrointestinal tract, leading to a condition known as 'iron-pill gastritis'.

This report highlights a rare case of 'iron pill-induced duodenitis', where a female patient in her 50s exhibited unusual duodenal iron deposition and mucosal injury, indicating that oral iron supplements can also affect the duodenum, not just the stomach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Iron pill-induced duodenitis: A distinct pattern of duodenal mucosal injury in a patient with a duodenal mass. Jeung, J., Ashour, S., Fuller, L.[2021]

Oral iron supplementation with ferrous sulfate (FeSO₄) leads to significantly higher levels of non-transferrin-bound iron (NTBI) in the bloodstream compared to other iron compounds, which raises safety concerns for young children with malaria.

In contrast, iron compounds like sodium iron ethylenediaminetetraacetic acid (NaFeEDTA) and iron polymaltose show negligible NTBI responses, suggesting they may be safer alternatives for iron supplementation in areas where malaria is prevalent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral administration of ferrous sulfate, but not of iron polymaltose or sodium iron ethylenediaminetetraacetic acid (NaFeEDTA), results in a substantial increase of non-transferrin-bound iron in healthy iron-adequate men. Schümann, K., Solomons, NW., Romero-Abal, ME., et al.[2022]

A new high-performance liquid chromatography (HPLC) method was developed to quickly and accurately measure elemental iron in ferrous sulfate tablets, which are used to treat iron deficiency anemia.

This method is validated for quality control and can effectively separate the iron from other components in the tablets within 5 minutes, ensuring the stability and reliability of the product throughout its shelf life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development and validation of an HPLC stability-indicating method for identification and assay of elemental iron(II) in pharmaceutical drug products using reversed-phase HPLC. Dias, NC., Rustum, AM.[2019]

In a cross-over trial involving patients undergoing renal dialysis, both oral iron (ferrous sulfate) and intravenous iron (iron dextran) were found to be equally effective, with no significant differences in therapeutic outcomes or side effects.

Each treatment was administered for 26 weeks, and both forms provided the same amount of elemental iron (100 mg), indicating that patients can choose either method without compromising safety or efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The therapeutic equivalence of oral and intravenous iron in renal dialysis patients. Strickland, ID., Chaput de Saintonge, DM., Boulton, FE., et al.[2013]

In a pilot study involving 9 healthy young males, ferrous iron sulfate was found to have superior bioavailability compared to ferric iron citrate preparations, indicating it is more effectively absorbed by the body.

Both types of iron preparations were compatible at therapeutic doses, but the study suggests that ferric iron preparations may be unsuitable for effective treatment since they need to be converted to bivalent iron for absorption, which may not occur sufficiently in the gastrointestinal tract.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Investigations of the bioavailability of iron from bi- and trivalent iron salts (author's transl)]. Dietzfelbinger, H., Kaboth, W.[2013]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2657918/

Iron Therapy for Preterm Infants - PMC The purpose of this article is to review the predisposing factors and consequences of iron deficiency and iron overload in the preterm infant.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6888764/

Iron supplementation in preterm and low-birth-weight infants Long-term iron supplementation appears to result in improved iron status and a reduction in iron deficiency and anemia in preterm and LBW infants.

3. haematologica.org haematologica.org/article/view/haematol.2024.284967

Oral iron supplementation: new formulations, old questions Oral iron supplementation is usually efficacious in correcting iron deficiency anemia and replenishing iron stores but causes gastrointestinal side effects ...

4. researchgate.net researchgate.net/publication/12144716_Iron_supplementation_in_preterm_infants_A_study_comparing_the_effect_and_tolerance_of_a_Fe2_and_a_nonionic_FeIII_compound

Iron Supplementation in Preterm Infants: A Study ... The more widely used divalent forms of iron (Fe2+) supplementation often lead to gastrointestinal symptoms in preterm infants although ...

5. mdpi.com mdpi.com/2227-9032/12/10/1043

Use of Different Iron Preparations for Prophylaxis and ... In our country, iron prophylaxis of 2 mg/kg/day has been recommended from the second month of life in premature babies regardless of nutritional ...

6. health.vic.gov.au health.vic.gov.au/patient-care/supplements-for-the-preterm-infant

Supplements for the preterm infant Ferrous Sulphate Oral liquid: contains 150 mg / 5 mL ferrous sulphate, equivalent to 30 mg / 5 mL of elemental iron. Recommended doses for ...

7. publications.aap.org publications.aap.org/pediatriccare/drug-monograph/18/5047/Ferrous-Sulfate

Ferrous Sulfate | Drug Lookup | Pediatric Care Online Premature infants: Avoid use in premature infants until the vitamin E stores, deficient at birth, are replenished. Dosage form specific issues: • Oral iron ...

8. bmcpediatr.biomedcentral.com bmcpediatr.biomedcentral.com/articles/10.1186/1471-2431-12-99

Benefits of Iron supplementation for low birth weight infants Iron supplementation increases the levels of hematologic indicators of iron status and reduces the prevalence of IDA/ID in low birth weight/premature infants.