IV vs Oral Iron for Anemia during Pregnancy

(IVIDA2 Trial)

Recruiting at 9 trial locations

Overseen By Steven Fein, MD

Age: 18 - 65

Sex: Female

Trial Phase: Phase 3

Sponsor: Women and Infants Hospital of Rhode Island

Disqualifiers: Thalassemia, Sickle cell, B12 deficiency, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 1

Duration: Up to delivery

300 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two iron treatments to determine which is more effective for pregnant women with iron-deficiency anemia. One group receives iron through an IV (a needle in the vein) using Ferric derisomaltose (also known as Monoferric), while the other takes iron pills, specifically Ferrous sulfate. The goal is to determine if IV iron can more effectively reduce health problems in mothers and enhance babies' brain development. Pregnant women at 13-30 weeks, diagnosed with iron-deficiency anemia, and planning to deliver at a participating hospital might be suitable candidates. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to significant advancements in maternal and infant health.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

In a previous study, researchers found that IV iron treatments, such as ferric derisomaltose, are generally safe for pregnant women. Most participants reported feeling better, with fewer symptoms like shortness of breath and tiredness. Another large study confirmed that IV iron is both safe and effective for treating anemia during pregnancy.

Regarding ferrous sulfate, studies have shown it helps prevent iron deficiency anemia and its negative effects on pregnancy and infant health. However, some research suggests that women receiving IV iron experienced fewer unwanted side effects compared to those taking oral iron like ferrous sulfate.

Overall, both treatments have been used safely during pregnancy, but IV iron might have fewer side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard of care, which typically involves oral iron supplements like ferrous sulfate, ferric derisomaltose offers a unique approach to treating anemia during pregnancy. This treatment is administered as a single intravenous (IV) infusion, which can deliver a high dose of iron directly into the bloodstream, potentially allowing for faster and more efficient treatment compared to daily oral tablets. Researchers are excited because this method may improve iron levels more quickly and effectively, especially for those who have difficulty tolerating oral iron supplements.

What evidence suggests that this trial's treatments could be effective for anemia during pregnancy?

This trial will compare the effectiveness of IV iron with oral iron for treating anemia during pregnancy. Research has shown that receiving iron intravenously, specifically with ferric derisomaltose, is more effective than taking iron pills for this purpose. Studies have found that IV iron significantly increases hemoglobin (a protein in red blood cells) and ferritin (a protein that stores iron) levels in pregnant women. One large study found that IV iron is a safe and effective treatment for anemia and can reduce the number of clinic visits, as it allows for higher doses and requires less time to administer compared to other IV iron treatments. Conversely, taking iron pills, such as ferrous sulfate, is also effective and has been shown to lower the risk of iron deficiency and anemia when taken daily. However, IV iron appears to increase hemoglobin levels more and is less likely to cause side effects than iron pills. ^{1 3 6 7 8}

Who Is on the Research Team?

Methodius Tuuli, MD, MPH, MBA

Principal Investigator

Women and Infants Hospital of Rhode Island

Are You a Good Fit for This Trial?

Pregnant women aged 18-45 with moderate-to-severe iron-deficiency anemia, at 24-28 weeks gestation, planning to deliver at a participating hospital. Excluded are those unable to consent or communicate with the team, carrying multiple babies, having certain digestive conditions or sensitivities to iron treatments, and non-iron-related anemias.

Inclusion Criteria

I am a pregnant woman aged 18-45.

Singleton gestation

Plan to deliver at participating hospital

Exclusion Criteria

Planned delivery at a non-study affiliated hospital

I cannot communicate with the study team even with an interpreter.

Inability or unwillingness to provide informed consent

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either a single IV infusion of 1000 mg ferric derisomaltose or oral iron tablets until delivery

Up to delivery

1 visit (in-person) for IV infusion, regular visits for oral iron monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment, including maternal and neonatal outcomes

6 weeks postpartum

Multiple visits (in-person and/or virtual)

Postpartum Monitoring

Monitoring of maternal and neonatal health outcomes, including neurodevelopment assessments

Up to 36 months for neurodevelopment assessments

What Are the Treatments Tested in This Trial?

Interventions

• Ferric derisomaltose
• Ferrous sulfate

Trial Overview This study is testing if IV iron (Ferric derisomaltose) is more effective and cost-efficient than oral iron (Ferrous sulfate) for pregnant women with low hemoglobin and ferritin levels. It's a double-blind trial meaning neither participants nor researchers know who gets which treatment.

How Is the Trial Designed?

Group I: IV Iron Experimental Treatment 1 Intervention

Participants assigned to the IV iron group will receive a single IV infusion of 1000 mg ferric derisomaltose (Monoferric, Pharmacosmos Therapeutics Inc., Morristown, NJ) in 250 mL given over 20 minutes and daily placebo tablets until delivery.

Group II: Oral Iron Active Control 1 Intervention

Participants assigned to the oral iron group will receive a single 250 mL IV normal saline infusion given over 20 minutes and 325mg tablets of ferrous sulfate (65 mg of elemental iron) to be taken until delivery.

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

Approved in United States as Monoferric for:

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

Approved in European Union as Monoferric for:

• Iron deficiency anemia in adult patients with chronic kidney disease when oral iron preparations are ineffective, cannot be used or for whom there is a clinical need for rapid increase in iron stores

Who Is Running the Clinical Trial?

Women and Infants Hospital of Rhode Island

Lead Sponsor

Trials

119

Recruited

59,200+

University of Utah

Collaborator

Trials

1,169

Recruited

1,623,000+

University of Alabama at Birmingham

Collaborator

Trials

1,677

Recruited

2,458,000+

Oregon Health and Science University

Collaborator

Trials

1,024

Recruited

7,420,000+

GNP Research at Heme-on-Call

Collaborator

Hasbro Children's Hospital

Collaborator

Trials

5

Recruited

10,100+

University of Michigan

Collaborator

Trials

1,891

Recruited

6,458,000+

Washington University School of Medicine

Collaborator

Trials

2,027

Recruited

2,353,000+

Published Research Related to This Trial

In a study involving 100 pregnant women with iron deficiency anemia, both bovine lactoferrin and ferrous sulfate effectively increased hemoglobin and iron levels after 30 days of treatment, showing similar efficacy.

Bovine lactoferrin was associated with significantly fewer gastrointestinal side effects, such as abdominal pain and constipation, compared to ferrous sulfate, making it a potentially safer option for treating iron deficiency in pregnant women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and tolerability of oral bovine lactoferrin compared to ferrous sulfate in pregnant women with iron deficiency anemia: a prospective controlled randomized study. Nappi, C., Tommaselli, GA., Morra, I., et al.[2014]

Intravenous iron sucrose significantly increased ferritin levels compared to oral iron sulfate at both 30 days and at delivery, indicating better iron stores replenishment in pregnant women with anemia.

Both treatments improved hemoglobin levels, but intravenous iron sucrose showed a trend towards higher birth weights, suggesting potential benefits for the baby, while being safe with no serious side effects reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Iron therapy in iron deficiency anemia in pregnancy: intravenous route versus oral route. Bayoumeu, F., Subiran-Buisset, C., Baka, NE., et al.[2022]

In a study of 112 pregnant women with iron deficiency anemia, intravenous iron sucrose significantly increased hemoglobin levels more than oral ferrous fumarate after 4 weeks (22 ± 11.5 g/L vs 12 ± 9 g/L, p < 0.0001).

The intravenous group also showed a greater improvement in serum ferritin levels, with 55% of participants experiencing a hemoglobin increase of more than 20 g/L, compared to only 11% in the oral group, indicating that intravenous iron sucrose is more effective for correcting anemia and replenishing iron stores during pregnancy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous iron sucrose v/s oral ferrous fumarate for treatment of anemia in pregnancy. A randomized controlled trial. Bhavi, SB., Jaju, PB.[2018]

In a study involving 201 pregnant women with iron deficiency, intravenous (IV) iron treatment resulted in 91% of participants remaining non-anaemic, compared to only 73% in those receiving oral iron, demonstrating a significant advantage for IV iron (p < 0.001).

IV iron not only improved haemoglobin levels more effectively than oral iron over an 18-week period but also led to greater reductions in fatigue and enhancements in quality of life, with similar safety profiles between the two treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous ferric derisomaltose versus oral iron for persistent iron deficient pregnant women: a randomised controlled trial. Hansen, R., Sommer, VM., Pinborg, A., et al.[2023]

In a randomized controlled trial with 124 pregnant participants, intravenous ferumoxytol significantly increased maternal hemoglobin levels by an average of 1.86 g/dL compared to only 0.79 g/dL with oral ferrous sulfate (P<.0001).

Intravenous ferumoxytol also resulted in greater improvements in iron indices, with significant increases in ferritin and iron levels, indicating it is a more effective treatment for iron-deficiency anemia in pregnancy than oral iron supplements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous infusions of ferumoxytol compared to oral ferrous sulfate for the treatment of anemia in pregnancy: a randomized controlled trial. Awomolo, AM., McWhirter, A., Sadler, LC., et al.[2023]

In a study of 150 pregnant women with anemia, daily administration of ferrous sulfate (60 mg) was found to be the most effective treatment, achieving a cure rate of 47% compared to 34% for twice a week and 27% for once a week.

While daily treatment was the most effective, it also led to more side effects like diarrhea and epigastric pain, suggesting that twice a week dosing is a viable alternative for those who cannot tolerate daily iron supplementation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The effectiveness of three regimens using ferrous sulfate to treat anemia in pregnant women]. de Souza, AI., Batista Filho, M., Ferreira, LO., et al.[2019]

A study involving 120 pregnant women found that ferrous sulfate, ferrous fumarate, ferrous ascorbate, and carbonyl iron were equally effective in treating iron-deficiency anemia, as all improved hemoglobin levels and other blood parameters similarly.

While all iron preparations were cost-effective, ferrous fumarate had a higher incidence of adverse effects (56.7%), suggesting that it may be less tolerable compared to the other options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized controlled trial comparing the efficacy, tolerability, and cost of oral iron preparations in iron-deficiency anemia in pregnancy. Gamad, N., Saha, PK., Sharma, P., et al.[2021]

In a study of pregnant Korean women with iron-deficiency anemia, ferric carboxymaltose (FCM) showed comparable increases in hemoglobin levels to oral ferrous sulfate (FS) after 3 weeks, but FCM significantly improved iron parameters and quality of life measures.

Both treatments were well tolerated, but FCM may be a better option for treating iron-deficiency anemia during pregnancy due to its superior effects on iron levels and overall well-being.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of ferric carboxymaltose versus ferrous sulfate for iron deficiency anemia during pregnancy: subgroup analysis of Korean women. Shim, JY., Kim, MY., Kim, YJ., et al.[2018]

In a randomized controlled trial involving 268 pregnant women with moderate iron deficiency anemia, intravenous iron sucrose was found to be superior to oral ferrous sulfate in terms of tolerability and effectiveness in correcting anemia.

Intravenous iron sucrose led to a quicker increase in hemoglobin and serum ferritin levels without major side effects, making it a preferable treatment option for pregnant women in remote areas with limited access to healthcare.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized Controlled Trial Comparing Ferrous Sulfate and Iron Sucrose in Iron Deficiency Anemia in Pregnancy. Chauhan, N., Dogra, P., Sharma, R., et al.[2023]

In a study of 252 pregnant women with iron deficiency anemia, intravenous ferric carboxymaltose (FCM) was found to correct anemia more effectively than oral ferrous sulfate (FS), with 84% of women achieving hemoglobin levels of at least 11.0 g/dL compared to 70% for FS.

FCM not only provided quicker anemia correction (median 3.4 weeks vs. 4.3 weeks for FS) but also improved quality of life measures such as vitality and social functioning, while having fewer gastrointestinal side effects compared to FS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ferric carboxymaltose vs. oral iron in the treatment of pregnant women with iron deficiency anemia: an international, open-label, randomized controlled trial (FER-ASAP). Breymann, C., Milman, N., Mezzacasa, A., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10435604/

Intravenous ferric derisomaltose versus oral iron for ... The trial results show that IV iron is superior to oral iron in preventing anaemia and improving Hb and ferritin levels in pregnant women with ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1701216325001938

Ferric Derisomaltose Versus Iron Sucrose in Pregnancy ... Compared to IS, FD significantly reduced infusion times and the number of clinic visits for patients, while delivering higher doses of IV iron with higher ...

3. smfm.org smfm.org/news/large-study-finds-iv-iron-treatment-during-pregnancy-safe-and-effective-for-anemia

Large Study Finds IV Iron Treatment During Pregnancy ... One of the largest studies of its kind finds early intervention with iron delivered intravenously during pregnancy is a safe and effective treatment for anemia.

4. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/5256/527288/Single-Dose-IV-Ferric-Derisomaltose-1000mg-given

Single-Dose IV Ferric Derisomaltose (1000mg given over 20 ... Results: The primary outcome is the resolution of iron deficiency anemia, defined as a 1 g/dL increase in Hgb at 6 weeks postpartum following ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05763043

NCT05763043 | Monoferric for Prenatal Iron Deficiency A prospective observational study of pregnant women with iron deficiency anemia and oral iron intolerance or advanced gestational age.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39651609/

Effect and safety of intravenous iron compared to oral ... Authors' conclusions: Intravenous iron likely slightly increases Hb levels and likely reduces anaemia in pregnancy compared to oral iron. Hb ...

7. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/2381/502723/Efficacy-Safety-and-Tolerability-of-Iron-Infusions

Efficacy, Safety, and Tolerability of Iron Infusions in Pregnant ... Among these pregnant women who received iron infusions, 94% reported improvement of one or more symptoms (shortness of breath, fatigue, or ice ...

8. droracle.ai droracle.ai/articles/18829/monoferric-and-pregnancy-safety

What is the safety of Monoferric (ferric derisomaltose) ... The safety of Monoferric during pregnancy is not well established, and healthcare providers typically prefer oral iron supplements as first-line ...