Daily vs. Every Other Day Oral Iron Supplementation in Patients With Absolute Iron Deficiency Anemia (DEODO)

Daily vs. Every Other Day Oral Iron Supplementation in Patients With Absolute Iron Deficiency Anemia (DEODO): a Multi-centered, Pilot Randomized Controlled Trial

Iron deficiency anemia is a global health problem and the most common cause of anemia worldwide. Patients with iron deficiency (ID) and IDA can present with a multitude of symptoms including fatigue, restless legs syndrome and pica.Oral iron supplementation is associated with increasing hemoglobin in multiple studies in women, pregnant women and elderly patients.However, the optimal dose and frequency of oral iron supplementation for treatment remains unclear. The current proposed study attempts to address this gap in the literature.

Study Overview

• Status: Completed
• Conditions: Anemia; Iron Deficiency Anemia
• Intervention / Treatment: Drug: Ferrous Sulfate 300Mg Tablet; Drug: Vitamin C 500Mg tablet

Detailed Description

This is a pilot, pragmatic, non-inferiority, open label randomized controlled trial (RCT) in outpatients with iron deficiency anemia to evaluate the effectiveness of oral ferrous sulfate 300mg (60mg elemental iron) once daily versus every other day to improve hemoglobin at 12 weeks post-initiation. The rationale for this study includes: (1) IDA is a common and prevalent condition with potential adverse consequences if left untreated; (2) optimizing effectiveness of oral iron supplementation while minimizing side effects will improve treatment for patients.

Because IDA is a global health problem, common in clinical practice and treatable, this study will have a significant practical impact on how clinicians treat outpatients with iron deficiency anemia and how patients tolerate therapy.

For the patient, the expected benefit from taking part in this study is the potential to improve and treat iron deficiency anemia. These potential changes may lead to improved symptoms associated with iron deficiency anemia, such as cognitive and physical functioning, and fatigue.

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Health Sciences Centre
    • Toronto, Ontario, Canada, M5B 1W8
      • St. Michael's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥ 16 years;
• Outpatients with iron deficiency anemia defined as Hb less than 120 g/L in women or 130g/L in men; AND ferritin less than 30 mcg/L

Exclusion Criteria:

• • Pregnancy

  • Currently breastfeeding
  • Known history of inflammatory bowel disease
  • Known history of celiac disease
  • Known history of thalassemia or thalassemia trait
  • Known inherited bleeding disorder
  • Known intolerance or lack of response to oral ferrous gluconate, sulfate or fumarate in the last 12 weeks
  • Multivitamin and mineral supplements (35 mg or more of elemental iron per day) in the 2 weeks prior to randomization
  • Allergy to oral iron
  • Allergy to any of the following medicinal and non-medicinal ingredients in ferrous sulfate: ferrous sulphate, calcium citrate, crospovidone, FD&C Red #40-Aluminum lake, FD&C Yellow #6-Aluminum Lake, magnesium stearate, microcrystalline cellulose, polyethylene glycol, polyvinyl alcohol, purified water, talc titanium dioxide
  • Allergy to any of the following medicinal and non-medicinal ingredients in vitamin C: Ascorbic acid, Colloidal silicon dioxide, croscarmellose sodium, magnesium stearate, microcrystalline cellulose and stearic acid
  • Intravenous iron therapy in the past 12 weeks
  • On anticoagulant therapy (e.g. warfarin, apixaban, dabigatran, edoxaban, rivaroxaban) initiated in the past 6 months
  • Surgery planned in upcoming 12 weeks
  • Chemotherapy planned in upcoming 12 weeks
  • Blood donation planned in upcoming 12 weeks
  • Previously enrolled in the study
  • Creatinine clearance less than 30 mL/min
  • Hemoglobin less than 80 g/L with active bleeding (defined as WHO grade 2 bleeding or higher in the past week)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Ferrous Sulfate and Vitamin C every other day; Ferrous sulfate 300mg tablet and vitamin C 500mg tablet taken by mouth every other day for 12 weeks	Drug: Ferrous Sulfate 300Mg Tablet; oral dose of Ferrous Sulfate (300 mg) every day versus every other day along with vitamin C; Other Names: Oral iron; Iron; Drug: Vitamin C 500Mg tablet; Vitamin C 500 Mg tablet every day versus every other day along with ferrous sulfate; Other Names: Ascorbic acid
ACTIVE_COMPARATOR: Ferrous Sulfate and Vitamin C daily; Ferrous sulfate 300mg tablet and vitamin C 500mg tablet taken by mouth every day for 12 weeks	Drug: Ferrous Sulfate 300Mg Tablet; oral dose of Ferrous Sulfate (300 mg) every day versus every other day along with vitamin C; Other Names: Oral iron; Iron; Drug: Vitamin C 500Mg tablet; Vitamin C 500 Mg tablet every day versus every other day along with ferrous sulfate; Other Names: Ascorbic acid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Enrollment	Enrollment in the trial will be defined as documentation of informed consent for patients approached	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of eligible participants consenting to participate	Proportion of eligible patients consenting to participate	2 years
Proportion of consenting patients receiving the allocated treatment	Proportion of consenting patients receiving the allocated treatment	2 years
Treated patients completing 4 and 12 week laboratory tests	Proportion of treated patients completing 4 week and 12 week laboratory tests	2 years
Proportion of treated patients completing side effect questionnaire at week 4, 8 and 12	Proportion of treated patients completing 4 week, 8 week and 12 week side effect questionnaire	2 years
Proportion of treated patients completing 4 week, 8 week and 12 week FACIT-fatigue scale	Proportion of treated patients completing 4 week, 8 week and 12 week FACIT-fatigue scale	2 years
Proportion of treatment doses taken per protocol based on pill count	Proportion of treatment doses taken as per protocol based on pill count	12 weeks
Proportion of treated patients taking 90% of prescribed doses	Proportion of treated patients taking at least 90% of their prescribed doses	2 years
Proportion of treated patients requiring a step down in therapy	Proportion of treated patients requiring a step down in therapy	2 years
Hemoglobin increment	Hemoglobin increment at 4 and 12 weeks is defined as the 4 or 12 week hemoglobin value minus the baseline hemoglobin value	12 weeks
Proportion with complete hemoglobin response	Proportion with complete hemoglobin response defined as hemoglobin greater than or equal to 120 g/L in women; and 130 g/L in men at 4 weeks and 12 weeks	2 years
Reticulocyte count	Change in reticulocyte count at 4 and 12 weeks defined as the 4 or 12 week reticulocyte count minus the baseline reticulocyte count	12 weeks
Change in ferritin, at 12 weeks defined as the value at 12 weeks minus the baseline value	Change in ferritin, at 12 weeks defined as the value at 12 weeks minus the baseline value	12 weeks
Change in serum iron at 12 weeks defined as the value at 12 weeks minus the baseline value	Change in serum iron at 12 weeks defined as the value at 12 weeks minus the baseline value	12 weeks
Change in TSAT at 12 weeks defined as the value at 12 weeks minus the baseline value	Change in TSAT at 12 weeks defined as the value at 12 weeks minus the baseline value	12 weeks
FACIT-fatigue scale at 4, 8 and 12 weeks	Quality of life (FACIT-fatigue scale) at 4, 8 and 12 weeks	12 weeks
Proportion with side effects and type of side effects at 4, 8 and 12 weeks as determined by the oral iron side effect questionnaire	Proportion with side effects and type of side effects at 4, 8 and 12 weeks as determined by the oral iron side effect questionnaire	12 weeks
Proportion of patients who stop taking oral iron due to side effects at 4 and 12 weeks	Proportion of patients who stop taking oral iron due to side effects at 4 and 12 weeks	12 weeks
Number of patients in need of escalation therapy	Need for escalation in therapy (increase in oral iron regimen from every other day to daily, need for intravenous iron, need for transfusion, visit to emergency department related to anemia) assessed at 12 weeks	2 years
Proportion of patients with a drop in hemoglobin of 10 g/L or more at weeks 4 and 12	Proportion of patients with a drop in hemoglobin of 10 g/L or more at weeks 4 and 12	2 years

Collaborators and Investigators

• Sponsor: Sunnybrook Health Sciences Centre
• Collaborators: Unity Health Toronto
• Investigators: Principal Investigator: Dr.Yulia Lin, Sunnybrook Health Sciences Center

Publications and helpful links

General Publications

• Kron A, Del Giudice ME, Sholzberg M, Callum J, Cserti-Gazdewich C, Swarup V, Huang M, Distefano L, Anani W, Skeate R, Armali C, Lin Y. 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. Pilot Feasibility Stud. 2022 May 4;8(1):98. doi: 10.1186/s40814-022-01042-y.

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 4, 2019
• Primary Completion (ACTUAL): January 26, 2022
• Study Completion (ACTUAL): January 26, 2022

Study Registration Dates

• First Submitted: October 23, 2018
• First Submitted That Met QC Criteria: October 29, 2018
• First Posted (ACTUAL): October 31, 2018

Study Record Updates

• Last Update Posted (ACTUAL): May 5, 2022
• Last Update Submitted That Met QC Criteria: May 4, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: hemoglobin; Anemia; Iron deficiency; Ferrous sulfate; oral iron
• Additional Relevant MeSH Terms: Metabolic Diseases; Hematologic Diseases; Nutrition Disorders; Anemia, Hypochromic; Iron Metabolism Disorders; Malnutrition; Anemia, Iron-Deficiency; Anemia; Deficiency Diseases; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Protective Agents; Trace Elements; Micronutrients; Vitamins; Antioxidants; Ascorbic Acid; Iron
• Other Study ID Numbers: CTO ID 1534

Drug and device information, study documents

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