Intravenous Versus Oral Iron for Treating Iron-Deficiency Anemia in Pregnancy

NCT ID: NCT05462704

Last Updated: 2025-06-10

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 300 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-01-17
• Study Completion Date: 2027-03-31

Brief Summary

Double blind, placebo controlled, multicenter randomized trial in pregnant women in the U.S. (N=300) to test the central hypothesis that IV iron in pregnant women with IDA (Hb<11 g/dL and ferritin<30 ng/mL) at 13 - 30 weeks will be effective, safe and cost-effective in reducing severe maternal morbidity-as measured by maternal anemia at delivery-and will also improve offspring neurodevelopment.

Detailed Description

Iron-deficiency anemia (IDA) is a common, undertreated problem in pregnancy. According to data from the U.S. National Health and Nutrition Examination Survey (NHANES), 25% of pregnant women in the U.S. have iron deficiency, with rates of 7%, 24%, and 39% in the first, second, and third trimesters, respectively. The prevalence of IDA is estimated at 16.2% overall and up to 30% at delivery. Iron deficiency is associated with significant adverse maternal and fetal outcomes including blood transfusion, cesarean delivery, depression, preterm birth, and low birth weight. Moreover, iron-deficient mothers are at risk of delivering iron-deficient neonates who, despite iron repletion, remain at risk for delayed growth and development. While treatment with iron supplementation is recommended during pregnancy, questions remain about the optimal route of delivery. Oral iron therapy, the current standard, is often suboptimal: up to 70% of patients experience significant gastrointestinal side effects (nausea, constipation, diarrhea, indigestion, and metallic taste) that prevent adherence to treatment, resulting in persistent anemia. Intravenous (IV) iron is an attractive alternative because it mitigates the adherence and absorption challenges of oral iron. However, IV iron costs more, and there are historical concerns about adverse reactions.

The American College of Obstetricians and Gynecologists (ACOG) recommends oral iron for the treatment of IDA in pregnancy, with IV iron reserved for the restricted group of patients. Our preliminary data show that this approach leads to 30% of patients with persistent IDA at delivery and an associated 3 to 6-fold increased risk of peripartum blood transfusion. ACOG's preferential recommendation of oral iron is based on paucity of data on the benefits and safety of IV iron, compared with oral iron, in pregnancy. Our published systematic review and meta-analysis showed that IV iron is associated with greater increase in maternal hemoglobin (Hb), but most of the primary trials were conducted in developing countries, included small sample sizes (50 - 252), and did not assess meaningful maternal and neonatal outcomes. The current Cochrane review noted that despite the high incidence and disease burden associated with IDA in pregnancy, there is paucity of quality trials assessing clinical maternal and neonatal effects of iron administration in women with anemia. The authors called for "large, good quality trials assessing clinical outcomes." The only large randomized trial of IV versus oral iron, conducted in India, showed no difference in a maternal composite outcome, but it is limited by use of iron sucrose which required five infusions, resulting in a wide range of iron doses (200 - 1600 mg). In addition, the primary composite outcome included some components not directly related to anemia. In contrast, our pilot trial of a single infusion of 1000 mg of IV low molecular weight iron dextran in pregnant women in the U.S. with moderate-to-severe IDA significantly reduced the rate of maternal anemia at delivery and showed promise for improving maternal morbidity by reducing rates of blood transfusion.

This is the first definitive double blind, placebo controlled, multicenter randomized trial in pregnant women in the U.S. (N=300) to test the central hypothesis that IV iron in pregnant women with IDA (Hb<11 g/dL and ferritin<30 ng/mL) at 13 - 30 weeks will be effective, safe and cost-effective in reducing severe maternal morbidity-as measured by maternal anemia at delivery-and will also improve offspring neurodevelopment. A multidisciplinary team of investigators in the U.S., will pursue the following specific aims:

Primary Aim: Evaluate the effectiveness and safety of IV iron, compared with oral iron, in reducing the rate of anemia at delivery in pregnant women with IDA.

Secondary Aim 1: Estimate the cost-effectiveness of IV iron , compared with oral iron, in pregnant women with IDA as measured by incremental cost per Quality Adjusted Life-year (QALY).

Secondary Aim 2: Assess the effect of IV iron, compared with oral iron, on offspring brain myelin content and neurodevelopment.

Conditions

Iron Deficiency Anemia; Pregnancy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

IV Iron

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 Type: EXPERIMENTAL

Ferric derisomaltose

Intervention Type: DRUG

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.

Oral Iron

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.

Group Type: ACTIVE_COMPARATOR

Ferrous sulfate

Intervention Type: DRUG

325mg ferrous sulfate tablets (65 mg of elemental iron), 1 to 3 orally per day.

Interventions

Ferric derisomaltose

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.

Intervention Type: DRUG

Ferrous sulfate

325mg ferrous sulfate tablets (65 mg of elemental iron), 1 to 3 orally per day.

Intervention Type: DRUG

Other Intervention Names

Monoferric; Ferosul

Eligibility Criteria

Inclusion Criteria

• Pregnant women between the ages of 18-45
• Singleton gestation
• Iron-deficiency anemia (serum ferritin <30ng/mL and Hb<11 g/dL)
• At 13-30 weeks gestation
• Plan to deliver at participating hospital

Exclusion Criteria

• Non-iron-deficiency anemia e.g thalassemia, sickle cell disease, B12 or folate deficiency, hypersplenism.
• Malabsorptive syndrome, inflammatory bowel disease, gastric bypass, or sensitivity to oral or IV iron
• Multiple gestation
• Inability or unwillingness to provide informed consent
• Inability to communicate with members of the study team, despite the presence of an interpreter
• Planned delivery at a non-study affiliated hospital

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Hasbro Children's Hospital

OTHER

Sponsor Role: collaborator

University of Michigan

OTHER

Sponsor Role: collaborator

Washington University School of Medicine

OTHER

Sponsor Role: collaborator

University of Utah

OTHER

Sponsor Role: collaborator

University of Alabama at Birmingham

OTHER

Sponsor Role: collaborator

Oregon Health and Science University

OTHER

Sponsor Role: collaborator

GNP Research at Heme-on-Call

UNKNOWN

Sponsor Role: collaborator

Women and Infants Hospital of Rhode Island

OTHER

Sponsor Role: lead

Responsible Party

Methodius Tuuli

Professor and Chair of Obstetrics and Gynecology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Methodius Tuuli, MD, MPH, MBA

Role: PRINCIPAL_INVESTIGATOR

Women and Infants Hospital of Rhode Island

Locations

University of Alabama Medical Center

Birmingham, Alabama, United States

Site Status: RECRUITING

GNP Research at Heme-on-Call

Miami, Florida, United States

Site Status: RECRUITING

Michigan University Medical Center

Ann Arbor, Michigan, United States

Site Status: RECRUITING

Washington University Medical Center

St Louis, Missouri, United States

Site Status: RECRUITING

Oregon Health and Sciences Uiversity Medical Center

Portland, Oregon, United States

Site Status: RECRUITING

Hasbro Children's Hospital

Providence, Rhode Island, United States

Site Status: RECRUITING

Women & Infants Hospital of Rhode Island

Providence, Rhode Island, United States

Site Status: RECRUITING

University of Utah Hospital

Salt Lake City, Utah, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Crystal Ware, BSN, CCRP

Role: CONTACT

cware@wihri.org

401-274-1122

Facility Contacts

Carolyn Webster, MD

Role: primary

Steven Fein, MD

Role: primary

Molly Stout, MD, MSCI

Role: primary

Ebony Carter, MD, MPH

Role: primary

Ashley Benson, MD

Role: primary

Viren D'sa, MD

Role: primary

Methodius Tuuli, MD, MPH, MBA

Role: primary

Ann Bruno, MD

Role: primary

Other Identifiers

Pro00060930

Identifier Type: -

Identifier Source: org_study_id