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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Anemia, Iron Deficiency Anemia

Intervention / Treatment
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* Drug: Ferrous Sulfate 300Mg Tablet
* Drug: Vitamin C 500Mg tablet


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ferrous Sulfate and Vitamin C every other day<br>Ferrous sulfate 300mg tablet and vitamin C 500mg tablet taken by mouth every other day for 12 weeks | Drug: Ferrous Sulfate 300Mg Tablet<br>* oral dose of Ferrous Sulfate (300 mg) every day versus every other day along with vitamin C<br>* Other names: Oral iron;Drug: Vitamin C 500Mg tablet<br>* Vitamin C 500 Mg tablet every day versus every other day along with ferrous sulfate<br>* Other names: Ascorbic acid;|
| Active Comparator: Ferrous Sulfate and Vitamin C daily<br>Ferrous sulfate 300mg tablet and vitamin C 500mg tablet taken by mouth every day for 12 weeks | Drug: Ferrous Sulfate 300Mg Tablet<br>* oral dose of Ferrous Sulfate (300 mg) every day versus every other day along with vitamin C<br>* Other names: Oral iron;Drug: Vitamin C 500Mg tablet<br>* Vitamin C 500 Mg tablet every day versus every other day along with ferrous sulfate<br>* Other names: Ascorbic acid;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Anemia, Iron deficiency, hemoglobin, oral iron, Ferrous sulfate