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

Phase 3

Completed

Conditions: Anemia
Iron Deficiency Anemia

Interventions: Drug: Ferrous Sulfate 300Mg Tablet
Drug: Vitamin C 500Mg tablet

Registration Number: NCT03725384

Lead Sponsor: Sunnybrook Health Sciences Centre

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 51

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 & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Ferrous Sulfate and Vitamin C every other day	Vitamin C 500Mg tablet	Ferrous sulfate 300mg tablet and vitamin C 500mg tablet taken by mouth every other day for 12 weeks
Ferrous Sulfate and Vitamin C daily	Vitamin C 500Mg tablet	Ferrous sulfate 300mg tablet and vitamin C 500mg tablet taken by mouth every day for 12 weeks
Ferrous Sulfate and Vitamin C every other day	Ferrous Sulfate 300Mg Tablet	Ferrous sulfate 300mg tablet and vitamin C 500mg tablet taken by mouth every other day for 12 weeks
Ferrous Sulfate and Vitamin C daily	Ferrous Sulfate 300Mg Tablet	Ferrous sulfate 300mg tablet and vitamin C 500mg tablet taken by mouth every day for 12 weeks

Primary Outcome Measures

Name	Time	Method
Feasibility of Enrolling Patients in the Trial	2 years	Enrollment in the trial will be defined as documentation of informed consent for patients approached. The primary outcome of this study is the feasibility of enrolling 52 participants in the trial over a 2-year period. Eligibility based on lab criteria was determined after consent.

Secondary Outcome Measures

Name	Time	Method
Proportion of Eligible Participants Consenting	2 years	Proportion of eligible patients after initial inclusion/exclusion screening that consent to participating in the study. Eligibility based on lab criteria was determined after consent.
Proportion of Patients Receiving the Allocated Treatment	2 years	Proportion of patients who signed informed consent and received the allocated treatment they were randomly assigned to.
Proportion of Patients Completing Laboratory Tests	2 years	Proportion of treated patients who completed both 4 week and 12 week laboratory tests
Proportion of Treated Patients Completing Side Effect Questionnaire at Week 4, 8 and 12	2 years	Proportion of treated patients completing 4 week, 8 week and 12 week side effect questionnaire
Proportion of Patients Completing FACIT-fatigue Scale	2 years	Proportion of patients who received treatment and completed 4 week, 8 week and 12 week FACIT-fatigue scale
Adherence to Treatment	2 years	Adherence was measured by the proportion of treated patients who took at least 90% of their prescribed doses
Proportion of Treated Patients Requiring a Step Down in Therapy	2 years	Proportion of treated patients requiring a step down in therapy by Week 4 and Week 12 (same proportions at both time points).
Hemoglobin Increment	12 weeks	Hemoglobin increment at 4 and 12 weeks is defined as the 4 or 12 week hemoglobin value minus the baseline hemoglobin value
Proportion With Complete Hemoglobin Response	2 years	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
Reticulocyte Count	12 weeks	Change in reticulocyte count at 4 and 12 weeks defined as the 4 or 12 week reticulocyte count minus the baseline reticulocyte count
Change in Ferritin at 12 Weeks	12 weeks	Change in ferritin at 12 weeks, defined as the value at 12 weeks minus the baseline value.
Change in Serum Iron at 12 Weeks	12 weeks	Change in serum iron at 12 weeks defined as the value at 12 weeks minus the baseline value
Change in TSAT at 12 Weeks	12 weeks	Change in transferrin saturation (TSAT) at 12 weeks defined as the value at 12 weeks minus the baseline value. Interquartile range represents Q1 (25th percentile) to Q3 (75th percentile)
FACIT-fatigue Score at 4, 8 and 12 Weeks	12 weeks	Quality of life (FACIT-fatigue scale) at 4, 8 and 12 weeks. Functional Assessment of Chronic Illness Therapy (FACIT) - fatigue scale. On this scale, lower scores indicate better symptoms and higher scores represent worse symptoms. The FACIT-fatigue scale has a range from 0 to 52.
Proportion of Patients With Side Effects at 4, 8 and 12 Weeks	12 weeks	Proportion of patients with side effects at 4, 8 and 12 weeks, as determined by the oral iron side effect questionnaire
Proportion of Patients Who Stopped Oral Iron Due to Side Effects	12 weeks	Number of patients who discontinued oral iron therapy due to side effects by week 12.
Number of Patients in Need of Escalation Therapy	2 years	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
Proportion of Patients With a Drop in Hemoglobin at Weeks 4 and 12	2 years	Proportion of patients with a drop in hemoglobin of 10 g/L or more at weeks 4 and 12
Types of Adverse Effects at 4 Weeks	4 Weeks	Proportion of patients with each type of adverse event at week 4.