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

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether participants must stop taking their current medications.

What data supports the effectiveness of the drug ferrous sulfate for premature infants?

Ferrous sulfate is commonly used to treat iron deficiency anemia, and studies have shown that it is effective in increasing iron levels in the body. It is often prescribed to prevent iron deficiency anemia in infants, which is a common condition. ^{1 2 3 4 5}

How does the drug ferrous sulfate differ from other treatments for premature infants?

Ferrous sulfate is unique because it is a bivalent iron salt that is more easily absorbed in the body compared to trivalent iron preparations, making it a more effective option for treating iron deficiency anemia in infants. Additionally, it is commonly prescribed as a preventive therapy for iron deficiency anemia in young infants, which is a widespread issue. ^{1 3 4 6 7}

What is the purpose of this trial?

Study focuses on determining if daily versus every-other-day (EOD) oral iron at the same dose per kilogram per day will achieve similar incidence of iron replete status at 36 weeks post-menstrual age in premature neonates

Research Team

Pratik K Parikh, MD

Principal Investigator

CHRISTUS Health

Richelle L Homo, MD

Principal Investigator

CHRISTUS Health; Brooke Army Medical Center

Eligibility Criteria

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 bleeding disorder.

My infant received iron injections before being assigned to a study group.

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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 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]

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]

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]

References

1. Sweden 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. [2021]

2. Germany pubmed.ncbi.nlm.nih.gov

Iron pill-induced duodenitis: A distinct pattern of duodenal mucosal injury in a patient with a duodenal mass. [2021]

3. England 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. [2019]

4. Mexico pubmed.ncbi.nlm.nih.gov

Evaluation of the prescription pattern of ferrous sulfate as a therapy for preventing iron deficiency anemia in infants. [2022]

5. Germany pubmed.ncbi.nlm.nih.gov

The therapeutic equivalence of oral and intravenous iron in renal dialysis patients. [2013]

6. United States 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. [2022]

7. Germany pubmed.ncbi.nlm.nih.gov

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