Iron Replacement Therapy for Iron-Deficiency Anemia

(IDA Trial)

Recruiting at 3 trial locations

Overseen By Silvie Suriany, MSc

Age: < 65

Sex: Female

Trial Phase: Phase 4

Sponsor: Children's Hospital Los Angeles

Disqualifiers: Diabetes, Hypertension, Morbid obesity, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

120 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore how iron deficiency anemia (IDA) affects the brain and whether iron replacement can enhance brain function and blood flow in adult women with moderate to severe anemia. It will assess two treatments: standard oral iron supplements (ferrous sulfate) and an intravenous iron infusion (ferric carboxymaltose) followed by a daily iron pill. Women who have struggled with anemia and experience symptoms like fatigue might be suitable for the interventional arm. Those with normal iron levels can join as healthy controls for the observational part.

As a Phase 4 trial, the treatment is already FDA-approved and proven effective, aiming to understand how it benefits more patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it excludes people who need medication for diabetes or hypertension. It's best to discuss your specific medications with the trial team.

What is the safety track record for Ferric carboxymaltose and Ferrous sulfate?

Research shows that ferric carboxymaltose, one of the treatments under study, is generally safe and well-tolerated. Studies have found that it effectively raises hemoglobin levels with only a few minor side effects. Most patients experienced minimal adverse reactions. Ferrous sulfate, another treatment, is a common and FDA-approved option for iron deficiency anemia. It is generally safe, though some people might experience mild digestive issues like stomach upset or constipation. Overall, these treatments have undergone sufficient testing to demonstrate their safety for most people. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike traditional oral iron supplements like ferrous sulfate, which can take weeks to improve symptoms of iron-deficiency anemia and sometimes cause digestive side effects, ferric carboxymaltose offers a different approach. Researchers are excited about ferric carboxymaltose because it's administered intravenously, allowing for a higher dosage to be delivered directly into the bloodstream, which can replenish iron stores more rapidly. This method potentially leads to quicker symptom relief and is especially beneficial for those who can't tolerate or absorb oral iron well.

What evidence suggests that this trial's treatments could be effective for iron-deficiency anemia?

Research has shown that ferric carboxymaltose, which participants in this trial may receive as part of the intravenous (IV) iron treatment arm, effectively treats iron-deficiency anemia (IDA). Studies have found that it improves hemoglobin and ferritin levels, which are crucial for oxygen transport in the blood. In one study, a single dose of ferric carboxymaltose was safe and often outperformed other iron treatments. Another study found it more effective than iron pills, particularly in correcting anemia and iron deficiency. This treatment has successfully managed IDA in various patient groups, demonstrating its effectiveness. ^{6 7 8 9 10}

Who Is on the Research Team?

John Wood, MD,PhD

Principal Investigator

Children's Hospital Los Angeles

Are You a Good Fit for This Trial?

This trial is for adult women aged 18-60 with moderate to severe iron deficiency anemia (IDA). Participants must have specific lab results indicating IDA and a hemoglobin level ≤10.5 g/dl or hematocrit <32%. Exclusions include MRI contraindications, systemic inflammatory diseases, severe asthma, eczema, atopy, diabetes on medication, hypertension on medication, prior reaction to IV iron, severe respiratory/cardiac disease or morbid obesity.

Inclusion Criteria

In the observational group, the control group should have hemoglobin levels above 13.2 g/dl or hematocrit levels above 39.6%.

My blood tests show I have low hemoglobin or hematocrit levels.

I have iron deficiency anemia as diagnosed by a hematologist.

Exclusion Criteria

I had a reaction to intravenous iron in the past.

I am taking medication for high blood pressure.

I have severe heart or lung disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Observation

Comprehensive cerebrovascular MRI, bloodwork, patient-reported outcomes, and neurocognitive testing are collected from all subjects in the observational arm.

Baseline (Day 0)

1 visit (in-person)

Intervention

Eligible anemic subjects receive either intravenous iron therapy or standard oral iron therapy. Repeated tests are conducted to assess the effects and durability of iron therapy.

12 months

Multiple visits (in-person and virtual)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments at various time points including Day 14, Day 90, Day 180, and Day 365 post iron therapy.

12 months

Multiple visits (in-person and virtual)

What Are the Treatments Tested in This Trial?

Interventions

• Ferric carboxymaltose
• Ferrous sulfate

Trial Overview

The study aims to understand the impact of IDA on brain function and structure in women and test if these effects can be reversed by iron replacement therapy. It involves two treatments: NovaFerrum and Ferric derisomaltose. The trial has both observational (examining existing conditions) and interventional (testing new treatments) components.

How Is the Trial Designed?

Group I: Intravenous (IV) iron Experimental Treatment 2 Interventions

This group will receive intravenous iron (Ferric Derisomaltose) in a single dose of 20 mg/kg (max individual dose of 1000 mg). The drug is administered as an infusion over 30 minutes. 3 months after the infusion, they will receive a 9-month supply of Novaferrum pill to be taken once a day.

Group II: Standard of care iron Active Control 1 Intervention

This group will be referred to their primary care provider for oral iron therapy. If a participant cannot obtain care from a physician

Group III: Healthy Controls Active Control 1 Intervention

This group will only be participating in the observational part of the study and serve as our controls.

Ferric carboxymaltose is already approved in European Union, Canada, United States for the following indications:

Approved in European Union as Ferinject for:

• Iron deficiency anemia in adult and pediatric patients when oral iron preparations are not tolerated or are ineffective

Approved in Canada as Ferinject for:

• Iron deficiency anemia in adult and pediatric patients one year of age and older when oral iron preparations are not tolerated or are ineffective
• Iron deficiency in adult patients with heart failure and New York Heart Association (NYHA) class II/III to improve exercise capacity

Approved in United States as Ferinject for:

• Iron deficiency anemia in adult patients who have intolerance to oral iron or have had unsatisfactory response to oral iron

Who Is Running the Clinical Trial?

Children's Hospital Los Angeles

Lead Sponsor

Trials

257

Recruited

5,075,000+

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+

Published Research Related to This Trial

In a study of 264 geriatric patients (average age 76.9 years), intravenous ferric carboxymaltose significantly improved hemoglobin levels, serum ferritin, and transferrin saturation, indicating its efficacy in treating functional iron deficiency anemia.

The treatment was well tolerated with no severe adverse reactions reported, making ferric carboxymaltose a safe and effective option for elderly patients with anemia related to chronic conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy and tolerability of ferric carboxymaltose in geriatric patients with anemia. Data from three non-interventional studies]. Röhrig, G., Steinmetz, T., Stein, J., et al.[2022]

In a study involving 40 patients with iron deficiency anemia, both controlled-release ferrous glycine sulfate and ferrous fumarate were equally effective in increasing hemoglobin and other blood parameters over 4 weeks.

Ferrous glycine sulfate was associated with fewer gastrointestinal side effects compared to ferrous fumarate, suggesting it may be a better-tolerated option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparative trial of a controlled-release iron tablet preparation ('Ferrocontin' Continus) and ferrous fumarate tablets. Aronstam, A., Aston, DL.[2016]

Ferric carboxymaltose is an effective intravenous treatment for iron-deficiency anemia, rapidly improving hemoglobin levels and replenishing iron stores in various patient populations, including those with chronic kidney disease and inflammatory bowel disease, with a single dose of up to 1000 mg administered in 15 minutes.

The treatment is well tolerated, with mild to moderate side effects similar to those of oral iron supplements, and it shows a faster improvement in hemoglobin levels compared to ferrous sulfate, making it a preferred option for patients who cannot take oral iron.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ferric carboxymaltose: a review of its use in iron-deficiency anaemia. Lyseng-Williamson, KA., Keating, GM.[2022]

Ferric carboxymaltose is an effective intravenous iron treatment for iron deficiency, allowing for a single high dose infusion (up to 1000 mg) that can improve patient outcomes in conditions like chronic heart failure, as shown in two randomized trials (FAIR-HF and CONFIRM-HF).

It is generally well tolerated with a low risk of hypersensitivity reactions and fewer gastrointestinal side effects compared to oral iron supplements, making it a preferable option for replenishing iron stores in various populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ferric carboxymaltose: a review of its use in iron deficiency. Keating, GM.[2022]

Carboxymaltose iron (Ferinject®) is an effective intravenous treatment for iron deficiency anemia, especially when oral iron is ineffective or not tolerated.

While it has an excellent safety profile, hypophosphatemia can occur as a side effect, which may lead to mild to serious symptoms, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypophosphatemic osteomalacia, a side effect of iron carboxymaltose administration. Madero Velázquez, L., Muñoz Pérez, R., Rodríguez, A., et al.[2022]

In a study of 291 women with postpartum anemia, intravenous ferric carboxymaltose was found to be more effective than oral ferrous sulfate, leading to quicker and sustained increases in hemoglobin levels.

Ferric carboxymaltose was also associated with fewer drug-related adverse events, indicating it is a safer and better-tolerated option for treating postpartum iron deficiency anemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ferric carboxymaltose injection in the treatment of postpartum iron deficiency anemia: a randomized controlled clinical trial. Seid, MH., Derman, RJ., Baker, JB., et al.[2022]

Iron carboxymaltose is as effective as ferrous sulfate for treating postpartum iron deficiency anemia, achieving similar increases in hemoglobin levels in just 2 weeks compared to 12 weeks for ferrous sulfate.

Iron carboxymaltose is better tolerated than ferrous sulfate, with fewer gastrointestinal side effects and no safety concerns for breast-fed infants, making it a safer and more convenient treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative efficacy and safety of intravenous ferric carboxymaltose in the treatment of postpartum iron deficiency anemia. Breymann, C., Gliga, F., Bejenariu, C., et al.[2022]

In a study involving 543 participants, the wax-matrix tablet of ferrous sulfate was associated with significantly fewer adverse effects compared to conventional ferrous sulfate tablets.

Eighty-one percent of participants using the wax-matrix preparation reported no severe or moderate side effects, while only 50% of those taking the conventional tablets had the same experience, indicating better tolerability of the wax-matrix formulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse effects of iron supplementation: a comparative trial of a wax-matrix iron preparation and conventional ferrous sulfate tablets. Brock, C., Curry, H., Hanna, C., et al.[2014]

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Mean serum hemoglobin was 10.2 ± 1.4 g/dL at baseline. All patients were treated with at least one FCM dose at baseline, with 77.6% receiving a ...

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A slow single infusion of 1 gram of FCM is well-tolerated, safe, and effective in treating iron deficiency anemia (IDA) and surpasses other interventions.

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Conclusions: Intravenous-iron improved hemoglobin levels both in actively treated and not-actively treated cancer patients. The effect has been ...

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This Phase 2, non-randomized, multicenter study characterized the safety profile and determined appropriate dosing of ferric carboxymaltose (FCM) in children ...

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Effectiveness and safety of ferric carboxymaltose compared to ...

Parenteral therapy is effective in IDA, but FCM elevates hemoglobin level and restored iron stores faster than IS with minimum adverse drug reactions.

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Iron dextrans are associated with a substantial risk of fatal anaphylaxis (and high doses are not FDA approved). The available non-dextran irons must also be ...