Ferric Citrate in Iron Deficiency Anemia During Pregnancy

Official title

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

Overview

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.

Interventions

• Drug Ferric citrate 210 mg
  Oral ferric citrate 210 mg (providing 210 mg elemental iron daily), administered once daily for 8 weeks.
• 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.

Primary outcome measures

• Hemoglobin concentration [Time frame: 4 weeks]

Secondary outcome measures (12)

• Anemia [Time frame: 36 weeks of gestation and 6 weeks postpartum]
• Iron deficiency [Time frame: 36 weeks of gestation and 6 weeks postpartum]
• Health-related quality of life [Time frame: 4 weeks]
• Severe anemia [Time frame: 6 weeks postpartum]
• Serious maternal medical events [Time frame: 6 weeks postpartum]
• Neonatal birth weight [Time frame: At birth]
• Placental weight [Time frame: At birth]
• Gestational age-adjusted birth weight [Time frame: At birth]
• Incidence of abortion [Time frame: through study completion, an average of 20 weeks]
• Incidence of stillbirth [Time frame: During delivery]
• Incidence of preterm birth [Time frame: During delivery]
• Cord venous blood hemoglobin concentration [Time frame: At birth]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Bangladesh · 1 center

• Dhaka Medical College — Dhaka

Identifiers

NCT: NCT07381426 · IRB-DMC/2025/291

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗