Intravenous Iron Therapy for Iron Deficiency in Pregnancy

Overseen by Ryan Lett, MD, FRCPC

Age: 18 - 65

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Saskatchewan Health Authority - Regina Area

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

Ion deficiency anemia (IDA) is associated with poor neonatal outcomes and maternal morbidity. Iron replacement may be done with oral iron or intravenous iron, with intravenous iron being utilized later in pregnancy or if there is an inadequate response to oral iron in the first trimester. In Canada, iron sucrose has been used, however iron isomaltoside is as safe as other formulations of IV iron but can replete iron stores with a single visit. Replenishing iron stores reduces both maternal and neonatal risks and is supported by current guidelines. Iron status may play a role in depression, as well as anemia, bleeding and blood transfusion. The goal of this clinical trial: * Correct IDA with fewer visits and less impact on the healthcare system * Improve the health and well being of all pregnant women who are experiencing moderate to severe iron deficiency anemia.

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are currently being treated with IV iron products or have had a blood transfusion within 4 weeks prior to joining, you cannot participate.

What data supports the idea that Intravenous Iron Therapy for Iron Deficiency in Pregnancy is an effective treatment?

The available research shows that Intravenous Iron Therapy, such as iron sucrose and ferric derisomaltose, is effective in treating iron deficiency in pregnant women. Studies comparing intravenous iron to oral iron treatments, like ferrous fumarate, indicate that intravenous iron can be more effective. For example, one study found that intravenous iron sucrose increased hemoglobin levels more effectively than oral iron in pregnant women with moderate-to-severe anemia. Another study showed that ferric derisomaltose was more effective than oral iron in women with persistent iron deficiency. These findings suggest that intravenous iron therapy can be a better option for improving iron levels during pregnancy. ^{1 2 3 4 5}

What safety data exists for intravenous iron therapy in pregnancy?

Intravenous iron therapies, including iron isomaltoside (also known as ferric derisomaltose) and iron sucrose, have been evaluated for safety in various studies. Iron isomaltoside has been shown to be well tolerated with a low incidence of serious adverse reactions (0.6%) and hypersensitivity reactions (0.3%). It also allows for higher cumulative dosing in fewer administrations compared to iron sucrose. Iron sucrose has been compared to oral iron therapies and shown to be effective, though its safety profile in pregnancy is still being established. Overall, both treatments have demonstrated a low frequency of hypersensitivity reactions and cardiovascular events, indicating a favorable safety profile for use in iron deficiency anemia, including during pregnancy. ^{1 2 5 6 7}

Is the drug Iron Isomaltoside 1000, Iron Sucrose a promising treatment for iron deficiency in pregnancy?

Yes, Iron Isomaltoside 1000 and Iron Sucrose are promising treatments for iron deficiency in pregnancy. They work quickly to improve iron levels and are well tolerated, making them effective options for pregnant women who need a rapid increase in iron. ^{1 3 5 7 8}

Research Team

Ryan Lett, MD, FRCPC

Principal Investigator

Saskatchewan Health Authority - Regina Area

Eligibility Criteria

This trial is for pregnant women over 18 with moderate to severe iron deficiency anemia, defined by specific blood test results. They must be at least 13 weeks into their pregnancy and willing to attend all treatment and follow-up appointments. Women with kidney or heart disease, certain infections, iron utilization disorders, recent IV iron or transfusions, multiple pregnancies, serious allergies or other significant health issues are excluded.

Inclusion Criteria

You have low levels of hemoglobin, serum ferritin, or iron saturation, which indicate iron deficiency anemia.

I am 18 years old or older.

Willing to participate and attend all planned follow up visits

Exclusion Criteria

I have a rheumatic disease.

Current participation in any other interventional trial

I currently have an active infection.

Treatment Details

Interventions

• Iron Isomaltoside 1000 (Iron Replacement Therapy)
• Iron Sucrose (Iron Replacement Therapy)

Trial Overview The study compares two intravenous (IV) iron treatments: ferric derisomaltose (iron isomaltoside) versus the standard treatment of iron sucrose in pregnant women with iron deficiency anemia. The aim is to correct IDA effectively with fewer healthcare visits and improve maternal and neonatal health outcomes.

Participant Groups

Group I: Iron Sucrose Active Control 1 Intervention

Route: Intravenous Dosage: 100 mg/mL (maximum 300 mg per dose) Frequency: up to 3 doses per week or 1000 mg per week maximum Duration: until iron needs reached by simplified table

Group II: Iron Isomaltoside/ferric derisomaltose Active Control 1 Intervention

route: intravenous Dosage: 1000-1500 mg (100mg/mL), max dose 20mg/kg Frequency: max dose 1000 mg, if further doses required, must receive dosage divided Duration: one infusion or two infusions (dose dependent)

Iron Isomaltoside 1000 is already approved in Canada for the following indications:

Approved in Canada as Monoferric for:

• Iron deficiency anemia in adult patients who have intolerance to oral iron or have had unsatisfactory response to oral iron or who have non-hemodialysis dependent chronic kidney disease (NDD-CKD)

Who Is Running the Clinical Trial?

Saskatchewan Health Authority - Regina Area

Lead Sponsor

Trials

29

Recruited

5,400+

Saskatchewan Centre for Patient-Oriented Research

Collaborator

Trials

12

Recruited

2,000+

Findings from Research

A study involving 213 pregnant women showed that a single high-dose infusion of intravenous iron isomaltoside (IV-IIM) is safe, with only 4.7% experiencing mild hypersensitivity reactions that resolved quickly.

Maternal and fetal outcomes, including hemoglobin levels at delivery, were similar between women who received IV-IIM and those who did not, indicating that IV-IIM is effective for treating iron deficiency during pregnancy without adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of intravenous iron isomaltoside for iron deficiency and iron deficiency anemia in pregnancy. Wesström, J.[2020]

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 study of 40 women with postpartum anemia, intravenous iron-sucrose led to a significant increase in hemoglobin levels (2.4 g/dl) compared to oral ferrous fumarate (1.2 g/dl) by day 14.

Intravenous iron-sucrose was found to be more effective in raising hemoglobin levels more quickly than oral ferrous fumarate, and it was administered without any serious side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous iron in postpartum anemia. Jain, G., Palaria, U., Jha, SK.[2022]

A study involving 2018 pregnant women with moderate-to-severe iron deficiency anemia found that intravenous iron sucrose did not significantly improve clinical outcomes compared to standard oral iron therapy, leading to the trial being stopped due to futility.

Both treatment groups had similar rates of serious maternal and fetal adverse events, indicating that intravenous iron sucrose is not more effective than oral iron and does not pose additional safety risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and effectiveness of intravenous iron sucrose versus standard oral iron therapy in pregnant women with moderate-to-severe anaemia in India: a multicentre, open-label, phase 3, randomised, controlled trial. Neogi, SB., Devasenapathy, N., Singh, R., et al.[2020]

In a trial involving 1512 patients with iron deficiency anemia, a single dose of 1000 mg iron isomaltoside (IIM) was found to be as safe as iron sucrose (IS), with very low rates of serious hypersensitivity reactions (0.3% for IIM vs 0.4% for IS).

IIM not only met the non-inferiority criteria for hemoglobin change but also resulted in a significantly faster hematological response within the first two weeks compared to IS, which requires multiple doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A prospective, multi-center, randomized comparison of iron isomaltoside 1000 versus iron sucrose in patients with iron deficiency anemia; the FERWON-IDA trial. Auerbach, M., Henry, D., Derman, RJ., et al.[2021]

In a trial involving 511 patients with iron deficiency anemia (IDA), iron isomaltoside was found to be more effective than iron sucrose, leading to a quicker increase in hemoglobin levels, with a significant proportion of patients achieving an increase of ≥2 g/dL within 5 weeks.

Both iron treatments were well tolerated, with only 0.6% of patients experiencing serious adverse reactions, and iron isomaltoside allowed for higher cumulative dosing in fewer administrations compared to iron sucrose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized trial of iron isomaltoside versus iron sucrose in patients with iron deficiency anemia. Derman, R., Roman, E., Modiano, MR., et al.[2021]

High-dose intravenous ferric derisomaltose (Monofer®) infusions of 500 and 1000 mg effectively corrected iron deficiency and iron deficiency anemia in elderly patients, leading to rapid improvements in laboratory parameters and symptoms like fatigue.

Intravenous iron administration is a viable treatment option for patients who cannot tolerate oral iron or have poor absorption, potentially reducing morbidity and mortality associated with untreated iron deficiency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of high-dose intravenous iron in middle-aged to elderly iron-deficient patients. Khiatani, D., Tay, HS., Cushway, TR.[2022]

References

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

Safety of intravenous iron isomaltoside for iron deficiency and iron deficiency anemia in pregnancy. [2020]

2. 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]

3. Germany pubmed.ncbi.nlm.nih.gov

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

4. India pubmed.ncbi.nlm.nih.gov

Intravenous iron in postpartum anemia. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Safety and effectiveness of intravenous iron sucrose versus standard oral iron therapy in pregnant women with moderate-to-severe anaemia in India: a multicentre, open-label, phase 3, randomised, controlled trial. [2020]

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

A prospective, multi-center, randomized comparison of iron isomaltoside 1000 versus iron sucrose in patients with iron deficiency anemia; the FERWON-IDA trial. [2021]

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

A randomized trial of iron isomaltoside versus iron sucrose in patients with iron deficiency anemia. [2021]

8. Malaysia pubmed.ncbi.nlm.nih.gov

Efficacy of high-dose intravenous iron in middle-aged to elderly iron-deficient patients. [2022]