Daily versus every other day oral iron supplementation in patients with iron deficiency anemia (DEODO): study protocol for a phase 3 multicentered, pragmatic, open-label, pilot randomized controlled trial

Abstract

Background Iron deficiency anemia (IDA) accounts for the majority of anemia cases across the globe and can lead to impairments in both physical and cognitive functioning. Oral iron supplementation is the first line of treatment to improve the hemoglobin level for IDA patients. However, gaps still exist in understanding the appropriate dosing regimen of oral iron. The current trial proposes to evaluate the feasibility of performing this study to examine the effectiveness and side-effect profile of oral iron once daily versus every other day. Methods In this open-label, pilot, feasibility, randomized controlled trial, 52 outpatients over 16 years of age with IDA (defined as hemoglobin < 12.0 g/dL in females and < 13.0 g/dL in males and ferritin < 30 mcg/L) will be enrolled across two large academic hospitals. Participants are randomized in a 1:1 ratio to receive 300 mg oral ferrous sulfate (60 mg of elemental iron) either every day or every other day for 12 weeks. Participants are excluded if they are as follows: (1) pregnant and/or currently breastfeeding, (2) have a disease history that would impair response to oral iron (e.g., thalassemia, celiac disease), (3) intolerant and/or have an allergy to oral iron or vitamin C, (4) on new anticoagulants in the past 6 months, (5) received IV iron therapy in the past 12 weeks, (6) have surgery, chemotherapy, or blood donation planned in upcoming 12 weeks, (7) a creatinine clearance < 30 mL/min, or (8) hemoglobin less than 8.0 g/dL with active bleeding. The primary outcome is feasibility to enroll 52 participants in this trial over a 2-year period to determine the effectiveness of daily versus every other day oral iron supplementation on hemoglobin at 12 weeks post-initiation and side-effect profile. Discussion The results of this trial will provide additional evidence for an appropriate dosing schedule for treating patients with IDA with oral iron supplementation. Additional knowledge will be gained on how the dosing regimen of oral iron impacts quality of life and hemoglobin repletion in IDA patients. If this trial is deemed feasible, it will inform the development and implementation of a larger multicenter definitive trial. Trial registration ClinicalTrials.gov: NCT03725384. Registered 31 October 2018.

A pilot feasibility trial of daily versus every other day oral iron supplementation in patients with iron deficiency anaemia

“…Full protocol details were published 9 (Appendix S1) and approved by Health Canada (file no. 240558) and registered on Clini calTr ials.gov (NCT03725384).…”

Prevention and Management of Iron Deficiency/Iron-Deficiency Anemia in Women: An Asian Expert Consensus

“…Many expert groups and clinical guidelines recommend oral iron as first-line therapy for the treatment of uncomplicated ID/IDA in women [48,[65][66][67]. As ferrous iron is more bioavailable and effective at restoring Hb levels compared with ferric iron, oral ferrous iron remains the standard treatment option for ID/IDA [67,68]. The three most widely used oral ferrous iron preparations are ferrous sulfate, ferrous gluconate, and ferrous fumarate (Table 2) [48,68,69].…”

“…As ferrous iron is more bioavailable and effective at restoring Hb levels compared with ferric iron, oral ferrous iron remains the standard treatment option for ID/IDA [67,68]. The three most widely used oral ferrous iron preparations are ferrous sulfate, ferrous gluconate, and ferrous fumarate (Table 2) [48,68,69]. In an effort to ensure a positive pregnancy experience for women, the WHO recommends increasing daily elemental iron from the standard daily antenatal dose of 30-60 mg to 120 mg for pregnant and postpartum women diagnosed with IDA, until Hb levels are normalized [23,71].…”