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

Sunnybrook Health Sciences Centre51 enrolled

Overview

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.

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

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Eligibility

Sex: ALLMin age: 16 Years

Medical Language ↔ Plain English

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)

Outcomes

Primary Outcomes

Feasibility of Enrolling Patients in the Trial

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.

Time frame: 2 years

Secondary Outcomes

Proportion of Eligible Participants Consenting

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.

Time frame: 2 years

Proportion of Patients Receiving the Allocated Treatment

Proportion of patients who signed informed consent and received the allocated treatment they were randomly assigned to.

Time frame: 2 years

Proportion of Patients Completing Laboratory Tests

Proportion of treated patients who completed both 4 week and 12 week laboratory tests

Time frame: 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

Time frame: 2 years

Proportion of Patients Completing FACIT-fatigue Scale

Proportion of patients who received treatment and completed 4 week, 8 week and 12 week FACIT-fatigue scale

Time frame: 2 years

Adherence to Treatment

Adherence was measured by the proportion of treated patients who took at least 90% of their prescribed doses

Time frame: 2 years

Proportion of Treated Patients Requiring a Step Down in Therapy

Proportion of treated patients requiring a step down in therapy by Week 4 and Week 12 (same proportions at both time points).

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 12 weeks

Change in Ferritin at 12 Weeks

Change in ferritin at 12 weeks, defined as the value at 12 weeks minus the baseline value.

Time frame: 12 weeks

Change in Serum Iron at 12 Weeks

Change in serum iron at 12 weeks defined as the value at 12 weeks minus the baseline value

Time frame: 12 weeks

Change in TSAT at 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)

Time frame: 12 weeks

FACIT-fatigue Score at 4, 8 and 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.

Time frame: 12 weeks

Proportion of Patients With Side Effects at 4, 8 and 12 Weeks

Proportion of patients with side effects at 4, 8 and 12 weeks, as determined by the oral iron side effect questionnaire

Time frame: 12 weeks

Proportion of Patients Who Stopped Oral Iron Due to Side Effects

Number of patients who discontinued oral iron therapy due to side effects by week 12.

Time frame: 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

Time frame: 2 years

Proportion of Patients With a Drop in Hemoglobin at Weeks 4 and 12

Proportion of patients with a drop in hemoglobin of 10 g/L or more at weeks 4 and 12

Time frame: 2 years

Types of Adverse Effects at 4 Weeks

Proportion of patients with each type of adverse event at week 4.

Time frame: 4 Weeks

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

Overview

Conditions

Interventions

Eligibility

Locations (2)

Outcomes

Primary Outcomes

Secondary Outcomes