Alternate-Day Oral Ferrous Sulfate (Duroferon) vs Placebo in Adolescent Girls with Iron Deficiency: A Randomised Double‑Blind Pilot Feasibility Study

The primary objective is to assess the feasibility of administering Duroferon 100 mg on alternate days together with Iron Smart, compared with placebo plus Iron Smart, in adolescent girls with iron deficiency, and to determine the diagnostic performance of the IRON‑5 tool for identifying iron deficiency defined by ferritin <15 µg/L. Secondary objectives include:

• Evaluation of change in ferritin concentration from screening to follow‑up.
• Evaluation of change in haemoglobin, transferrin saturation, vitamin B12 and 25‑hydroxyvitamin D from screening to follow‑up.
• Identification of factors associated with iron deficiency such as dietary patterns, body‑mass index, menstrual characteristics, physical activity, socioeconomic status and country of birth.
• Investigation of factors other than iron deficiency that are related to fatigue and self‑rated quality of life, including vitamin B12/25‑hydroxyvitamin D status, anxiety/depression and lifestyle variables.

The trial enrolled female adolescents who were students at Polhemskolan in Lund, were post‑menarcheal, and met the age requirement of ≥15 years. All participants were required to have laboratory evidence of iron deficiency as indicated by a serum ferritin level below 30 µg/L. Written informed consent was obtained from each participant, and when applicable, from a legal guardian for individuals under 18 years of age. The sponsor did not provide information regarding the total number of participants enrolled in the study.

The pilot trial employs a randomized, double-blind, placebo-controlled design to compare alternate‑day oral administration of 100 mg ferrous sulfate (Duroferon) with matching placebo in adolescent girls diagnosed with iron deficiency. Eligible participants (≥15 years, post‑menarcheal, ferritin <30 µg/L) undergo a screening visit for consent, laboratory confirmation of ferritin level, and baseline assessments, followed by randomization and initiation of the assigned study medication. Subsequent follow‑up visits are scheduled at predefined intervals to monitor adherence, tolerability, and safety parameters, and to collect blood samples for ferritin, hemoglobin, TSAT, vitamin B12, and 25‑hydroxyvitamin D measurements. The final end‑of‑study visit, occurring after the intervention period, repeats all efficacy and safety evaluations and concludes study participation. Participant involvement therefore spans from the screening encounter through the end‑of‑study assessment, with the overall trial scheduled to run from January 1 2027 to September 30 2027.

The investigational product, Duroferon depottabletter, is a ferrous sulfate containing modified‑release tablet supplied in a 100 mg strength. The tablet is administered orally, with a single dose taken on alternate days throughout the treatment period.

The comparator is Duroferon placebo, which contains no active pharmaceutical ingredient and is matched in appearance to the active tablet. It is administered orally on the same alternate‑day schedule as the active product to maintain blinding.

All participants receive the educational programme “Iron Smart,” a non‑pharmacologic component that provides dietary guidance and iron‑status monitoring. Administration of both the active tablet and placebo follows the same dosing schedule, and adherence is assessed through pill counts, electronic dosing logs, and participant diaries to ensure compliance with the alternate‑day regimen.

Efficacy will be evaluated by quantifying the change in ferritin concentration and the changes in hemoglobin, transferrin saturation (TSAT), vitamin B12, and 25‑hydroxyvitamin D levels between the screening visit and the follow‑up assessment. Blood samples obtained at these two time points will be processed using standard laboratory assays to determine each biomarker. Secondary efficacy analyses will explore associations between iron deficiency status and selected variables, including dietary patterns, body‑mass index, menstrual characteristics, hormonal contraceptive use, physical activity, socioeconomic status, and country of birth, as well as relationships between fatigue, self‑rated quality of life, and other potential contributors such as vitamin B12 or vitamin D deficiency, anxiety/depression, and lifestyle factors.