IV vs Oral Iron for Anemia during Pregnancy

(IVIDA2 Trial)

Recruiting at 7 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

746 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests if giving iron through an IV drip can help pregnant women with severe anemia who can't tolerate oral iron. It aims to see if this method reduces the need for blood transfusions and improves baby development.

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.

What data supports the effectiveness of the drug Ferric derisomaltose for treating anemia during pregnancy?

Research shows that intravenous iron treatments like ferric derisomaltose can be more effective than oral iron supplements, such as ferrous sulfate, in treating anemia in pregnant women. Studies comparing similar treatments have found that IV iron often works better and faster in increasing iron levels in the body. ^{1 2 3 4 5}

Is it safe to use IV or oral iron for anemia during pregnancy?

Research shows that both intravenous (IV) iron treatments like ferric derisomaltose and ferric carboxymaltose, as well as oral iron treatments like ferrous sulfate, have been studied for safety in pregnant women with iron deficiency anemia. These studies generally indicate that both forms of iron are safe for use during pregnancy, although specific side effects and tolerability can vary between individuals. ^{1 2 3 6 7}

How does the drug Ferric derisomaltose differ from other treatments for anemia during pregnancy?

Ferric derisomaltose is given through an IV (intravenous, directly into the vein), which can work faster and be more effective for severe anemia compared to oral iron pills like ferrous sulfate, which are taken by mouth. ^{1 2 8 9 10}

Research Team

Methodius Tuuli, MD, MPH, MBA

Principal Investigator

Women and Infants Hospital of Rhode Island

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

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+

Findings from Research

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 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]

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 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]

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 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]

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]

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 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]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Intravenous ferric derisomaltose versus oral iron for persistent iron deficient pregnant women: a randomised controlled trial. [2023]

2. United States 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. [2023]

3. United States 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. [2014]

4. Australia 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. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

[The effectiveness of three regimens using ferrous sulfate to treat anemia in pregnant women]. [2019]

6. England 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. [2018]

7. Germany 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). [2022]

8. England pubmed.ncbi.nlm.nih.gov

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

9. United States pubmed.ncbi.nlm.nih.gov

Iron therapy in iron deficiency anemia in pregnancy: intravenous route versus oral route. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Randomized Controlled Trial Comparing Ferrous Sulfate and Iron Sucrose in Iron Deficiency Anemia in Pregnancy. [2023]