Ferric Citrate in Iron Deficiency Anemia During Pregnancy

Efficacy and Safety of Ferric Citrate in Iron Deficiency Anemia During the Second Trimester of Pregnancy in Bangladesh: A Randomized Controlled Trial

Maternal anemia remains a significant public health concern in low and middle income countries including Bangladesh, contributing to adverse maternal and neonatal outcomes. Despite the widespread use of oral ferrous fumarate, gastrointestinal intolerance and suboptimal adherence remain persistent challenges, indicating the need for alternative iron formulations with improved efficacy and safety profiles. Hence, this study aims to evaluate the efficacy and safety of oral ferric citrate compared to oral ferrous fumarate in the management of maternal iron deficiency anemia during second trimester of pregnancy.

This phase 3, open-label, two-arm, parallel-group randomized controlled trial will be conducted among pregnant women aged 18-35 years, with gestational age between 13 and 26 weeks, diagnosed with moderate to severe iron deficiency anemia (hemoglobin 7-9.9 g/dL and serum ferritin <30 μg/L). Exclusion criteria are non-iron deficiency anemia, multiple pregnancy, severe comorbidities, and recent intravenous iron therapy. Eligible participants will be randomized in a 1:1 ratio to receive either oral ferric citrate 210 mg (210 mg elemental iron) once daily for 8 weeks or oral ferrous fumarate 200 mg (66 mg elemental iron) twice daily for 12 weeks or until delivery, whichever occurs earlier.

The primary endpoint is the change in maternal hemoglobin concentration from baseline to week 4 of randomization. Secondary endpoints include maternal outcome such as prevalence of anemia and iron deficiency at 36 weeks gestation and at 6 weeks postpartum, changes in maternal health-related quality of life (assessed by EQ-5D-5L), incidence of severe anemia requiring transfusion, and serious maternal medical events and neonatal outcomes such as birth weight, placental weight, birth weight percentiles, rates of low birth weight, abortion, stillbirth, preterm birth, and cord blood hemoglobin and ferritin levels, as well as infant hemoglobin and iron indices at 6 weeks of age. Safety endpoints will include incidence of adverse events, serious adverse events, maternal sick visits during the follow-up period.

Ethical approval for this trial was obtained from the institutional review boards of Dhaka Medical College, and written informed consent will be secured from all participants prior to enrollment. The findings from this trial are expected to inform clinical guidelines by establishing whether ferric citrate offers a clinically advantageous alternative to Ferrous fumarate for managing iron deficiency anemia during pregnancy.

Study Overview

• Status: Not yet recruiting
• Conditions: Anemia
• Intervention / Treatment: Drug: Ferric citrate 210 mg; Drug: Ferrous fumarate 200 mg

• Study Type: Interventional
• Enrollment (Estimated): 680
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Arifa Sharmin Maya, FCPS, MCPS, FACS, DMU, MBBS; Phone Number: +8801733521479; Email: drarifasharmin@gmail.com

Study Locations

• Bangladesh
  • Dhaka, Bangladesh
    • Dhaka Medical College
    • Contact: Arifa Sharmin Maya, FCPS, MCPS, FACS, DMU, MBBS; Phone Number: +8801733521479; Email: drarifasharmin@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Pregnant women aged 18 to 35 years.
• Gestational age between 13 and 26 completed weeks, confirmed by last menstrual period and/or early ultrasound dating.
• Diagnosed with moderate to severe iron deficiency anemia (IDA), defined as:

Hemoglobin concentration between 7.0 g/dL and <9.9 g/dL, and Serum ferritin concentration <30 μg/L

• Singleton intrauterine pregnancy confirmed by ultrasonography.
• Willing to comply with study procedures and follow-up schedule up to 6 weeks postpartum.
• Euthyroid or euthyroid with medications
• Normal in anomaly scan
• Received ANC check up duly
• History of folic acid intake in ANC visit
• Willing to conduct delivery at the study center or at a facility within the study catchment area.
• No known plans to leave the study area before completion of follow-up.

Exclusion Criteria:

• Known hypersensitivity or intolerance to ferric citrate, ferrous fumarate, or any excipients in the formulations.
• Presence of non-iron deficiency anemia (e.g., megaloblastic anemia, hemoglobinopathies, hemolytic anemia, anemia of chronic disease) estimated by PBF
• Baseline hemoglobin concentration <7.0 g/dL or requiring urgent transfusion according to the best clinical judgement of the consultants
• Serum ferritin ≥30 μg/L at baseline.
• Severe concurrent medical conditions including:

Chronic kidney disease (Stage 3 or higher) Decompensated liver disease Active tuberculosis or other chronic infections Diagnosed malignancy

• Pre-existing preeclampsia, or eclampsia, or gestational hypertension
• Gestational diabetes or type 2 diabetes mellitus in the current pregnancy.
• Multiple pregnancy (e.g., twins, triplets).
• Gastrointestinal conditions affecting iron absorption (e.g., inflammatory bowel disease, celiac disease, previous gastric or intestinal surgery).
• Use of intravenous iron therapy within previous 2 weeks of the present trial.
• Any other condition which, in the opinion of the investigator, may jeopardize the participant's safety or interfere with study outcomes or compliance.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ferric citrate; Oral ferric citrate 210 mg (providing 210 mg elemental iron daily), administered once daily for 8 weeks.	Drug: Ferric citrate 210 mg; Oral ferric citrate 210 mg (providing 210 mg elemental iron daily), administered once daily for 8 weeks.
Active Comparator: Ferrous fumarate; Oral Ferrous fumarate 200 mg (providing 132 mg elemental iron daily), administered twice daily for 12 weeks or until delivery, whichever occurs earlier.	Drug: Ferrous fumarate 200 mg; Oral Ferrous fumarate 200 mg (providing 132 mg elemental iron daily), administered twice daily for 12 weeks or until delivery, whichever occurs earlier.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hemoglobin concentration	Change in maternal hemoglobin concentration (g/dL)	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anemia	Prevalence of maternal anemia (Hb <11g/dL)	36 weeks of gestation and 6 weeks postpartum
Iron deficiency	Prevalence of maternal iron deficiency (serum ferritin concentration <30 μg/L)	36 weeks of gestation and 6 weeks postpartum
Severe anemia	Incidence of severe anemia requiring blood transfusion during gestation, delivery, or the puerperium	6 weeks postpartum
Serious maternal medical events	Incidence of serious maternal medical events, including: Antepartum or postpartum hemorrhage Sepsis or septic shock Intensive care unit (ICU) admission Prolonged hospital stay Wound infection confirmed by positive growth in culture of wound swab Maternal mortality	6 weeks postpartum
Neonatal birth weight	Neonatal birth weight will be measured at birth (in grams)	At birth
Placental weight	Placental weight will be measured after delivery (in grams)	At birth
Gestational age-adjusted birth weight	Gestational age-adjusted birth weight will be measured at birth (in grams)	At birth
Incidence of abortion	Incidence of abortion	through study completion, an average of 20 weeks
Incidence of stillbirth	Incidence of stillbirth	During delivery
Incidence of preterm birth	Incidence of preterm birth	During delivery
Cord venous blood hemoglobin concentration	Cord venous blood hemoglobin concentration (g/dL) will be measured from umbilical cord blood samples collected immediately after delivery	At birth
Cord venous blood ferritin concentration	Cord venous blood ferritin concentration (ng/mL) will be measured from umbilical cord blood samples collected immediately after delivery.	At birth
Infant hemoglobin concentration	Infant hemoglobin concentration (g/dL) will be measured from peripheral venous blood samples collected at the 6-week of age	6 weeks after birth
Infant serum ferritin concentration	Infant serum ferritin concentration (ng/mL) will be measured from peripheral venous blood samples collected at 6 weeks of age	6 weeks after birth
Health-related quality of life	Change in maternal health-related quality of life (HRQoL) will be assessed using the EuroQol five-dimension, five-level questionnaire (EQ-5D-5L), a standardized instrument that evaluates five health dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is scored on a five-level ordinal scale ranging from level 1 (no problems) to level 5 (extreme problems), generating a five-digit health state that represents the respondent's self-reported health status. Raw EQ-5D-5L health states will subsequently be converted into a single summary index score using the country-specific value set for Bangladesh. The EQ-5D-5L index score ranges from values below 0, representing health states considered worse than death, to 1.0, representing full health. Higher index scores indicate better health-related quality of life. Changes in the EQ-5D-5L index score will be used to quantify changes in maternal HRQoL over the study period.	4 weeks

Collaborators and Investigators

• Sponsor: Dhaka Medical College
• Collaborators: Sir Salimullah Medical College and Midford Hospital; Mugdha Medical College and Hospital; Shaheed Suhrawardy Medical College and Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2026
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): March 31, 2027

Study Registration Dates

• First Submitted: January 4, 2026
• First Submitted That Met QC Criteria: January 25, 2026
• First Posted (Actual): February 2, 2026

Study Record Updates

• Last Update Posted (Actual): February 3, 2026
• Last Update Submitted That Met QC Criteria: January 31, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Anemia; Iron deficiency
• Additional Relevant MeSH Terms: Metabolic Diseases; Hematologic Diseases; Iron Metabolism Disorders; Nutritional and Metabolic Diseases; Hemic and Lymphatic Diseases; Iron Deficiencies; Anemia; ferric citrate; ferrous fumarate
• Other Study ID Numbers: IRB-DMC/2025/291

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: IPD will be shared on a reasonable request to the PI.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No