Daily Versus Alternate-Day Oral Iron Therapy for Anemia in Second-Trimester Pregnancy

Daily Versus Alternate-Day Oral Iron Therapy for Anemia Correction in Second-Trimester Pregnant Patients: A Randomized Controlled Trial

This randomized controlled trial compares daily versus alternate-day oral iron supplementation in pregnant women with iron deficiency anemia during the second trimester. The study evaluates changes in hemoglobin and serum ferritin, treatment adherence, and gastrointestinal side effects to inform more patient-centered, physiologically aligned dosing strategies.

Study Overview

• Status: Not yet recruiting
• Conditions: Iron Deficiency Anemia; Anemia in Pregnancy
• Intervention / Treatment: Drug: Ferrous Sulfate

Detailed Description

Iron deficiency anemia is the leading cause of anemia in pregnancy. Although daily oral iron is standard first-line therapy, it is frequently associated with gastrointestinal side effects and poor adherence. Because hepcidin rises after an iron dose and remains elevated for 24 to 48 hours, daily dosing may reduce fractional absorption; alternate-day dosing allows hepcidin to fall between doses, potentially improving absorption and tolerance.

This single-center, prospective, randomized, parallel-group trial will recruit pregnant women (13 to 27 weeks gestation) with hemoglobin below 11 g/dL and serum ferritin below 30 ng/mL from the antenatal clinic at PAF Teaching Hospital, Islamabad. Eligible, consenting participants will be randomized 1:1 to daily ferrous sulfate (one 325 mg tablet, approximately 65 mg elemental iron, once daily) or alternate-day ferrous sulfate (two 325 mg tablets, approximately 130 mg elemental iron, every other day) for four weeks.

The primary outcome is change in hemoglobin from baseline to Week 4. Secondary outcomes are change in serum ferritin, treatment adherence (proportion taking at least 80 percent of doses, by pill count and diary), and the frequency and severity of gastrointestinal side effects. Outcome assessors (laboratory personnel) are blinded to allocation; participant blinding is not feasible given the differing dosing schedules. Planned enrollment is 184 participants (92 per group), giving 90 percent power to detect a 0.40 g/dL difference in hemoglobin change at a two-sided alpha of 0.05, assuming a standard deviation of 0.83 g/dL.

• Study Type: Interventional
• Enrollment (Estimated): 184
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ammara Suleman; Phone Number: +92 321 5279502; Email: shazibnawaz2016@gmail.com

Study Locations

• Pakistan
  • Islamabad, Pakistan
    • Pakistan Air Force (PAF) Hospital Islamabad

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Aged 18 to 40 years
• Pregnant women in the second trimester (13 to 27 weeks gestation)
• Hemoglobin below 11 g/dL with serum ferritin below 30 ng/mL
• Singleton pregnancy

Exclusion Criteria:

• Known congenital or acquired hemoglobin disorders (e.g., thalassemia, hemoglobinopathies)
• Chronic diseases affecting hemoglobin levels (e.g., chronic kidney disease, inflammatory disorders)
• Bleeding disorders or a history of frequent blood loss
• Gastrointestinal conditions impairing nutrient absorption (e.g., celiac disease or other malabsorption syndromes)
• Currently receiving parenteral iron
• Requiring blood transfusion

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Daily Iron; One ferrous sulfate 325 mg tablet (approximately 65 mg elemental iron) once daily for four weeks.	Drug: Ferrous Sulfate; Oral ferrous sulfate 325 mg tablets (approximately 65 mg elemental iron per tablet) administered for four weeks according to the assigned dosing schedule. All participants receive standardized counseling on administration, diet, side effects, and adherence, and are issued a dose diary.
Experimental: Alternate-Day Iron; Two ferrous sulfate 325 mg tablets (approximately 130 mg elemental iron) every other day for four weeks.	Drug: Ferrous Sulfate; Oral ferrous sulfate 325 mg tablets (approximately 65 mg elemental iron per tablet) administered for four weeks according to the assigned dosing schedule. All participants receive standardized counseling on administration, diet, side effects, and adherence, and are issued a dose diary.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in hemoglobin from baseline to Week 4	Mean within-participant change in hemoglobin concentration (g/dL), measured at baseline and at Week 4, compared between the daily and alternate-day arms.	Baseline and Week 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in serum ferritin from baseline to Week 4	Mean within-participant change in serum ferritin concentration (ng/mL) from baseline to Week 4, compared between groups.	Baseline and Week 4
Treatment adherence	Proportion of participants taking at least 80 percent of prescribed doses, determined by pill count cross-checked against patient dose diaries.	Through Week 4
Frequency of gastrointestinal side effects	Proportion of participants reporting any gastrointestinal side effect (nausea, vomiting, constipation, metallic taste, or abdominal discomfort) recorded using a structured checklist.	Through Week 4
Severity of gastrointestinal side effects	Severity of reported gastrointestinal side effects graded as mild, moderate, or severe on a structured checklist.	Through Week 4

Collaborators and Investigators

• Sponsor: Pakistan Air Force (PAF) Hospital Islamabad
• Investigators: Principal Investigator: Ammara Suleman, MBBS, Pakistan Air Force (PAF) Hospital Islamabad

Study record dates

Study Major Dates

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

Study Registration Dates

• First Submitted: June 14, 2026
• First Submitted That Met QC Criteria: June 14, 2026
• First Posted (Actual): June 18, 2026

Study Record Updates

• Last Update Posted (Actual): June 18, 2026
• Last Update Submitted That Met QC Criteria: June 14, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: hepcidin; adherence; ferrous sulfate; second trimester; oral iron; alternate-day dosing
• Additional Relevant MeSH Terms: Metabolic Diseases; Hematologic Diseases; Anemia; Iron Metabolism Disorders; Anemia, Hypochromic; Nutritional and Metabolic Diseases; Hemic and Lymphatic Diseases; Iron Deficiencies; Anemia, Iron-Deficiency; ferrous sulfate
• Other Study ID Numbers: IRON-DvA-2026-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No