"Effect of Daily, Alternate-Day, and Every-Other-Day Oral Iron Supplementation on Gastrointestinal Adverse Effects and Treatment Efficacy in Women Aged 18–45 with Iron Deficiency

“Compare the therapeutic efficacy and gastrointestinal adverse events of oral iron supplementation administered daily, every other day, and every two days in the treatment of iron-deficiency anemia in women.”

Phase IV, randomized, three-arm parallel trial, double-blind, N=150; computer-generated allocation stratified by baseline Hb.

Outpatient clinics of Jahrom University of Medical Sciences; women aged 18–45; screening, baseline labs, randomisation, 8-week follow-up; participants and outcome assessors blinded.

Eligibility Conditions Women aged 18 to 45 years attending the clinics of Jahrom University of Medical Sciences Diagnosis of iron deficiency anemia based on: Hemoglobin 8–12 g/dL Serum ferritin < 30 ng/mL No use of oral or injectable iron in the past 12 weeks No history of surgery, chemotherapy, or blood donation in the past 12 weeks GFR > 30 mL/min No chronic inflammatory, renal, hepatic, or malignant disease No gastrointestinal disorders affecting iron absorption No history of severe allergy or intolerance to iron supplements Ability to understand study information and provide informed consent Discontinuation Criteria Voluntary withdrawal by the participant at any time Pregnancy occurring during the study period Development of serious adverse events related to iron supplementation Non-adherence, defined as taking < 80% of the prescribed supplement Initiation or continuous use of interfering medications A final diagnosis other than iron deficiency anemia Hospitalization or any clinical deterioration that prevents continuation of participation

Arm A: Daily oral iron; Arm B: Alternate-day oral iron; Arm C: Every–two-day oral iron;

Mean hemoglobin change from baseline to week 8; Frequency and severity of gastrointestinal adverse effects

Participants will be allocated to the study groups using variable block randomization based on a computer-generated random sequence. The unit of randomization is the individual eligible participant. To ensure balanced distribution of anemia severity between the groups, stratified randomization will be performed according to baseline hemoglobin levels in two strata (8 to <10 g/dL and 10 to 12 g/dL), with independent block randomization within each stratum. The random allocation sequence will be generated by an individual independent of the study team using statistical software, and variable block sizes will be applied without disclosure to investigators involved in participant enrollment. Allocation concealment will be ensured using sequentially numbered, opaque, sealed envelopes that will be opened only after eligibility has been confirmed for each participant. No quasi-random allocation methods will be used in this study.

Double-blind Both participants and outcome assessors (clinical staff and data analysts) will remain unaware of group assignments. Blinding will be maintained using matched placebo tablets to ensure identical appearance and dosing schedule across all study arms.

The collected data in this study include de-identified participant information, laboratory test results, treatment adherence, and primary and secondary clinical outcomes. All data will be anonymized before sharing. The dataset includes all primary and secondary outcome measures, as well as details of interventions and study groups.

Access to the data will be available starting six months after the publication of study results and will continue for five years thereafter.

Active researchers at academic and scientific institutions can request access to the data. Independent researchers with a relevant research proposal and ethical approval may also be granted access.

Data are permitted solely for scientific research purposes, and commercial use is prohibited. Statistical analyses must follow the submitted research protocol, and any publication must cite the source and ethical approval.

Applicants can contact Dr. Hossein Ali Rostamipour at Imam Reza Clinic, adjacent to Peymanieh Hospital, Jahrom. Contact details: Phone: +989177911197, Email: hossainroscawi41@yahoo.com

The applicant must complete and submit a formal request form, provide their research proposal, and ethical approval. After review by the study coordinator, approved data will be provided in a de-identified file. The process typically takes 2 to 4 weeks.

All data and documents will be stored and shared in accordance with privacy regulations and research ethical standards.