Anemia, Iron Deficiency Anemia
Conditions
Keywords
Anemia, Iron deficiency, hemoglobin, oral iron, Ferrous sulfate
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.
Interventions
DRUGFerrous Sulfate 300Mg Tablet
oral dose of Ferrous Sulfate (300 mg) every day versus every other day along with vitamin C
DRUGVitamin C 500Mg tablet
Vitamin C 500 Mg tablet every day versus every other day along with ferrous sulfate
Sponsors
Unity Health Toronto
Sunnybrook Health Sciences Centre
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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. |
| 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. |
| 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. |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Iron Daily Ferrous sulfate (iron) 300mg tablet and vitamin C 500mg tablet taken by mouth every day for 12 weeks | 24 |
| Iron Every Other Day Ferrous sulfate 300mg tablet and vitamin C 500mg tablet taken by mouth every other day for 12 weeks | 27 |
| Total | 51 |
Baseline characteristics
| Characteristic | Iron Daily | Iron Every Other Day | Total |
|---|---|---|---|
| Age, Continuous | 47.2 years STANDARD_DEVIATION 18.1 | 44.4 years STANDARD_DEVIATION 17.1 | 45.7 years STANDARD_DEVIATION 17.5 |
| Baseline C reactive protein | 0.9 mg/L | 1.0 mg/L | 0.9 mg/L |
| Baseline C reactive protein >/=5 mg/L | 1 Participants | 4 Participants | 5 Participants |
| Baseline creatinine | 0.83 mg/dL | 0.70 mg/dL | 0.78 mg/dL |
| Baseline ferritin | 9 mu grams/L | 9 mu grams/L | 9 mu grams/L |
| Baseline haemoglobin | 110 g/L STANDARD_DEVIATION 13 | 110 g/L STANDARD_DEVIATION 10 | 110 g/L STANDARD_DEVIATION 11 |
| Baseline haemoglobin <100 g/L | 3 Participants | 3 Participants | 6 Participants |
| Baseline mean corpuscular volume (MCV) | 80.0 fL STANDARD_DEVIATION 8.2 | 80.6 fL STANDARD_DEVIATION 8 | 80.3 fL STANDARD_DEVIATION 8.1 |
| Baseline reticulocyte count | 48 x10^9 cells/L | 47 x10^9 cells/L | 48 x10^9 cells/L |
| Baseline serum iron | 8 mu mol/L | 5 mu mol/L | 7 mu mol/L |
| Body Mass Index | 25.9 kg/m^2 STANDARD_DEVIATION 6.7 | 27.0 kg/m^2 STANDARD_DEVIATION 7 | 26.5 kg/m^2 STANDARD_DEVIATION 6.8 |
| History of bleeding in the past 2 months | 16 Participants | 23 Participants | 39 Participants |
| History of rheumatological disorders | 4 Participants | 3 Participants | 7 Participants |
| IV iron use in the past year | 1 Participants | 5 Participants | 6 Participants |
| Medication history Proton pump inhibitor | 1 Participants | 0 Participants | 1 Participants |
| Medication history Ranitidine | 0 Participants | 1 Participants | 1 Participants |
| Menstrual bleeding, pictorial blood assessment chart >/= 100 | 7 Participants | 16 Participants | 23 Participants |
| Oral iron use in the past year | 13 Participants | 13 Participants | 26 Participants |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Reason for iron deficient anemia (IDA) diagnosis Blood donation | 6 Participants | 3 Participants | 9 Participants |
| Reason for iron deficient anemia (IDA) diagnosis Gastrointestinal | 4 Participants | 4 Participants | 8 Participants |
| Reason for iron deficient anemia (IDA) diagnosis Menorrhagia | 11 Participants | 17 Participants | 28 Participants |
| Reason for iron deficient anemia (IDA) diagnosis Other | 3 Participants | 3 Participants | 6 Participants |
| Region of Enrollment Canada | 24 participants | 27 participants | 51 participants |
| Sex: Female, Male Female | 20 Participants | 21 Participants | 41 Participants |
| Sex: Female, Male Male | 4 Participants | 6 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 27 | 0 / 24 | 0 / 51 |
| other Total, other adverse events | 15 / 27 | 9 / 24 | 24 / 51 |
| serious Total, serious adverse events | 0 / 27 | 0 / 24 | 0 / 51 |
Outcome results
Primary
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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Total Number Screened for Eligbility | Feasibility of Enrolling Patients in the Trial | 85 participants |
Secondary
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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Total Number Screened for Eligbility | Adherence to Treatment | 0.78 Proportion of participants |
| Total Number Allocated to Iron Every Other Day | Adherence to Treatment | 0.82 Proportion of participants |
Secondary
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
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Total Number Screened for Eligbility | Change in Ferritin at 12 Weeks | Baseline ferritin | 9 mcg/L |
| Total Number Screened for Eligbility | Change in Ferritin at 12 Weeks | Week 12 ferritin | 30 mcg/L |
| Total Number Allocated to Iron Every Other Day | Change in Ferritin at 12 Weeks | Baseline ferritin | 9 mcg/L |
| Total Number Allocated to Iron Every Other Day | Change in Ferritin at 12 Weeks | Week 12 ferritin | 23 mcg/L |
| Total Number of Patients Allocated to Study Arms | Change in Ferritin at 12 Weeks | Baseline ferritin | 9 mcg/L |
| Total Number of Patients Allocated to Study Arms | Change in Ferritin at 12 Weeks | Week 12 ferritin | 27 mcg/L |
Secondary
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
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Total Number Screened for Eligbility | Change in Serum Iron at 12 Weeks | Baseline serum iron | 8 micro mol/L |
| Total Number Screened for Eligbility | Change in Serum Iron at 12 Weeks | Week 12 serum iron | 17 micro mol/L |
| Total Number Allocated to Iron Every Other Day | Change in Serum Iron at 12 Weeks | Baseline serum iron | 5 micro mol/L |
| Total Number Allocated to Iron Every Other Day | Change in Serum Iron at 12 Weeks | Week 12 serum iron | 12 micro mol/L |
| Total Number of Patients Allocated to Study Arms | Change in Serum Iron at 12 Weeks | Baseline serum iron | 7 micro mol/L |
| Total Number of Patients Allocated to Study Arms | Change in Serum Iron at 12 Weeks | Week 12 serum iron | 16 micro mol/L |
Secondary
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
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Total Number Screened for Eligbility | Change in TSAT at 12 Weeks | Baseline TSAT | 11 percentile |
| Total Number Screened for Eligbility | Change in TSAT at 12 Weeks | Week 12 TSAT | 26 percentile |
| Total Number Allocated to Iron Every Other Day | Change in TSAT at 12 Weeks | Baseline TSAT | 7 percentile |
| Total Number Allocated to Iron Every Other Day | Change in TSAT at 12 Weeks | Week 12 TSAT | 18 percentile |
| Total Number of Patients Allocated to Study Arms | Change in TSAT at 12 Weeks | Baseline TSAT | 9 percentile |
| Total Number of Patients Allocated to Study Arms | Change in TSAT at 12 Weeks | Week 12 TSAT | 23 percentile |
Secondary
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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Total Number Screened for Eligbility | FACIT-fatigue Score at 4, 8 and 12 Weeks | Week 8 FACIT-fatigue score | 21.5 score on a scale | Standard Deviation 8.5 |
| Total Number Screened for Eligbility | FACIT-fatigue Score at 4, 8 and 12 Weeks | Week 4 FACIT-fatigue score | 23.9 score on a scale | Standard Deviation 9.8 |
| Total Number Screened for Eligbility | FACIT-fatigue Score at 4, 8 and 12 Weeks | Week 12 FACIT-fatigue score | 20.1 score on a scale | Standard Deviation 8.5 |
| Total Number Allocated to Iron Every Other Day | FACIT-fatigue Score at 4, 8 and 12 Weeks | Week 8 FACIT-fatigue score | 24.9 score on a scale | Standard Deviation 11.4 |
| Total Number Allocated to Iron Every Other Day | FACIT-fatigue Score at 4, 8 and 12 Weeks | Week 4 FACIT-fatigue score | 26.3 score on a scale | Standard Deviation 9.7 |
| Total Number Allocated to Iron Every Other Day | FACIT-fatigue Score at 4, 8 and 12 Weeks | Week 12 FACIT-fatigue score | 21.9 score on a scale | Standard Deviation 9.9 |
| Total Number of Patients Allocated to Study Arms | FACIT-fatigue Score at 4, 8 and 12 Weeks | Week 4 FACIT-fatigue score | 25.2 score on a scale | Standard Deviation 9.7 |
| Total Number of Patients Allocated to Study Arms | FACIT-fatigue Score at 4, 8 and 12 Weeks | Week 12 FACIT-fatigue score | 21.0 score on a scale | Standard Deviation 9.3 |
| Total Number of Patients Allocated to Study Arms | FACIT-fatigue Score at 4, 8 and 12 Weeks | Week 8 FACIT-fatigue score | 23.4 score on a scale | Standard Deviation 10.2 |
Secondary
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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Total Number Screened for Eligbility | Hemoglobin Increment | Hemoglobin at 4 weeks | 122 g/L | Standard Deviation 7 |
| Total Number Screened for Eligbility | Hemoglobin Increment | Hemoglobin at baseline | 110 g/L | Standard Deviation 13 |
| Total Number Screened for Eligbility | Hemoglobin Increment | Hemoglobin at 12 weeks | 131 g/L | Standard Deviation 9 |
| Total Number Allocated to Iron Every Other Day | Hemoglobin Increment | Hemoglobin at 4 weeks | 119 g/L | Standard Deviation 10 |
| Total Number Allocated to Iron Every Other Day | Hemoglobin Increment | Hemoglobin at baseline | 110 g/L | Standard Deviation 10 |
| Total Number Allocated to Iron Every Other Day | Hemoglobin Increment | Hemoglobin at 12 weeks | 126 g/L | Standard Deviation 8 |
| Total Number of Patients Allocated to Study Arms | Hemoglobin Increment | Hemoglobin at baseline | 110 g/L | Standard Deviation 11 |
| Total Number of Patients Allocated to Study Arms | Hemoglobin Increment | Hemoglobin at 12 weeks | 129 g/L | Standard Deviation 9 |
| Total Number of Patients Allocated to Study Arms | Hemoglobin Increment | Hemoglobin at 4 weeks | 121 g/L | Standard Deviation 9 |
Secondary
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Total Number Screened for Eligbility | Number of Patients in Need of Escalation Therapy | 0 Participants |
| Total Number Allocated to Iron Every Other Day | Number of Patients in Need of Escalation Therapy | 0 Participants |
Secondary
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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Total Number Screened for Eligbility | Proportion of Eligible Participants Consenting | 0.39 Proportion of participants |
Secondary
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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Total Number Screened for Eligbility | Proportion of Patients Completing FACIT-fatigue Scale | 0.91 Proportion of participants |
| Total Number Allocated to Iron Every Other Day | Proportion of Patients Completing FACIT-fatigue Scale | 0.89 Proportion of participants |
Secondary
Proportion of Patients Completing Laboratory Tests
Proportion of treated patients who completed both 4 week and 12 week laboratory tests
Time frame: 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Total Number Screened for Eligbility | Proportion of Patients Completing Laboratory Tests | 0.91 Proportion of participants |
| Total Number Allocated to Iron Every Other Day | Proportion of Patients Completing Laboratory Tests | 0.81 Proportion of participants |
| Total Number of Patients Allocated to Study Arms | Proportion of Patients Completing Laboratory Tests | 0.86 Proportion of participants |
Secondary
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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Total Number Screened for Eligbility | Proportion of Patients Receiving the Allocated Treatment | 0.96 Proportion of participants |
| Total Number Allocated to Iron Every Other Day | Proportion of Patients Receiving the Allocated Treatment | 1 Proportion of participants |
| Total Number of Patients Allocated to Study Arms | Proportion of Patients Receiving the Allocated Treatment | 0.98 Proportion of participants |
Secondary
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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Total Number Screened for Eligbility | Proportion of Patients Who Stopped Oral Iron Due to Side Effects | 0 Proportion of participants |
| Total Number Allocated to Iron Every Other Day | Proportion of Patients Who Stopped Oral Iron Due to Side Effects | 0 Proportion of participants |
| Total Number of Patients Allocated to Study Arms | Proportion of Patients Who Stopped Oral Iron Due to Side Effects | 0 Proportion of participants |
Secondary
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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Total Number Screened for Eligbility | Proportion of Patients With a Drop in Hemoglobin at Weeks 4 and 12 | 0 Proportion of participants |
| Total Number Allocated to Iron Every Other Day | Proportion of Patients With a Drop in Hemoglobin at Weeks 4 and 12 | 0 Proportion of participants |
Secondary
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
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Total Number Screened for Eligbility | Proportion of Patients With Side Effects at 4, 8 and 12 Weeks | Week 8 | 0.33 Proportion of participants |
| Total Number Screened for Eligbility | Proportion of Patients With Side Effects at 4, 8 and 12 Weeks | Week 4 | 0.38 Proportion of participants |
| Total Number Screened for Eligbility | Proportion of Patients With Side Effects at 4, 8 and 12 Weeks | Week 12 | 0.33 Proportion of participants |
| Total Number Allocated to Iron Every Other Day | Proportion of Patients With Side Effects at 4, 8 and 12 Weeks | Week 8 | 0.48 Proportion of participants |
| Total Number Allocated to Iron Every Other Day | Proportion of Patients With Side Effects at 4, 8 and 12 Weeks | Week 4 | 0.56 Proportion of participants |
| Total Number Allocated to Iron Every Other Day | Proportion of Patients With Side Effects at 4, 8 and 12 Weeks | Week 12 | 0.44 Proportion of participants |
| Total Number of Patients Allocated to Study Arms | Proportion of Patients With Side Effects at 4, 8 and 12 Weeks | Week 4 | 0.47 Proportion of participants |
| Total Number of Patients Allocated to Study Arms | Proportion of Patients With Side Effects at 4, 8 and 12 Weeks | Week 12 | 0.39 Proportion of participants |
| Total Number of Patients Allocated to Study Arms | Proportion of Patients With Side Effects at 4, 8 and 12 Weeks | Week 8 | 0.41 Proportion of participants |
Secondary
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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Total Number Screened for Eligbility | Proportion of Treated Patients Completing Side Effect Questionnaire at Week 4, 8 and 12 | 0.91 Proportion of participants |
| Total Number Allocated to Iron Every Other Day | Proportion of Treated Patients Completing Side Effect Questionnaire at Week 4, 8 and 12 | 0.85 Proportion of participants |
Secondary
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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Total Number Screened for Eligbility | Proportion of Treated Patients Requiring a Step Down in Therapy | 0.13 Proportion of participants |
| Total Number Allocated to Iron Every Other Day | Proportion of Treated Patients Requiring a Step Down in Therapy | 0 Proportion of participants |
Secondary
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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Total Number Screened for Eligbility | Proportion With Complete Hemoglobin Response | 0.59 Proportion of participants |
| Total Number Allocated to Iron Every Other Day | Proportion With Complete Hemoglobin Response | 0.75 Proportion of participants |
Secondary
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
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Total Number Screened for Eligbility | Reticulocyte Count | Week 12 reticulocyte count | 47 x10^9 cells/ L |
| Total Number Screened for Eligbility | Reticulocyte Count | Week 4 reticulocyte count | 61 x10^9 cells/ L |
| Total Number Screened for Eligbility | Reticulocyte Count | Baseline reticulocyte count | 48 x10^9 cells/ L |
| Total Number Allocated to Iron Every Other Day | Reticulocyte Count | Week 4 reticulocyte count | 65 x10^9 cells/ L |
| Total Number Allocated to Iron Every Other Day | Reticulocyte Count | Baseline reticulocyte count | 47 x10^9 cells/ L |
| Total Number Allocated to Iron Every Other Day | Reticulocyte Count | Week 12 reticulocyte count | 52 x10^9 cells/ L |
| Total Number of Patients Allocated to Study Arms | Reticulocyte Count | Baseline reticulocyte count | 48 x10^9 cells/ L |
| Total Number of Patients Allocated to Study Arms | Reticulocyte Count | Week 12 reticulocyte count | 47 x10^9 cells/ L |
| Total Number of Patients Allocated to Study Arms | Reticulocyte Count | Week 4 reticulocyte count | 64 x10^9 cells/ L |
Secondary
Types of Adverse Effects at 4 Weeks
Proportion of patients with each type of adverse event at week 4.
Time frame: 4 Weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Total Number Screened for Eligbility | Types of Adverse Effects at 4 Weeks | Constipation | 0.25 Proportion of participants |
| Total Number Screened for Eligbility | Types of Adverse Effects at 4 Weeks | Breathlessness | 0.17 Proportion of participants |
| Total Number Screened for Eligbility | Types of Adverse Effects at 4 Weeks | Headache | 0.17 Proportion of participants |
| Total Number Screened for Eligbility | Types of Adverse Effects at 4 Weeks | Nausea | 0.17 Proportion of participants |
| Total Number Screened for Eligbility | Types of Adverse Effects at 4 Weeks | Heartburn | 0.08 Proportion of participants |
| Total Number Screened for Eligbility | Types of Adverse Effects at 4 Weeks | Other | 0.21 Proportion of participants |
| Total Number Screened for Eligbility | Types of Adverse Effects at 4 Weeks | Vomiting | 0.04 Proportion of participants |
| Total Number Screened for Eligbility | Types of Adverse Effects at 4 Weeks | Abdominal pain | 0.08 Proportion of participants |
| Total Number Screened for Eligbility | Types of Adverse Effects at 4 Weeks | Diarrhea | 0.08 Proportion of participants |
| Total Number Allocated to Iron Every Other Day | Types of Adverse Effects at 4 Weeks | Abdominal pain | 0.19 Proportion of participants |
| Total Number Allocated to Iron Every Other Day | Types of Adverse Effects at 4 Weeks | Diarrhea | 0.19 Proportion of participants |
| Total Number Allocated to Iron Every Other Day | Types of Adverse Effects at 4 Weeks | Vomiting | 0.11 Proportion of participants |
| Total Number Allocated to Iron Every Other Day | Types of Adverse Effects at 4 Weeks | Other | 0.22 Proportion of participants |
| Total Number Allocated to Iron Every Other Day | Types of Adverse Effects at 4 Weeks | Headache | 0.26 Proportion of participants |
| Total Number Allocated to Iron Every Other Day | Types of Adverse Effects at 4 Weeks | Breathlessness | 0.26 Proportion of participants |
| Total Number Allocated to Iron Every Other Day | Types of Adverse Effects at 4 Weeks | Heartburn | 0.30 Proportion of participants |
| Total Number Allocated to Iron Every Other Day | Types of Adverse Effects at 4 Weeks | Nausea | 0.26 Proportion of participants |
| Total Number Allocated to Iron Every Other Day | Types of Adverse Effects at 4 Weeks | Constipation | 0.22 Proportion of participants |
| Total Number of Patients Allocated to Study Arms | Types of Adverse Effects at 4 Weeks | Other | 0.22 Proportion of participants |
| Total Number of Patients Allocated to Study Arms | Types of Adverse Effects at 4 Weeks | Constipation | 0.24 Proportion of participants |
| Total Number of Patients Allocated to Study Arms | Types of Adverse Effects at 4 Weeks | Nausea | 0.22 Proportion of participants |
| Total Number of Patients Allocated to Study Arms | Types of Adverse Effects at 4 Weeks | Headache | 0.22 Proportion of participants |
| Total Number of Patients Allocated to Study Arms | Types of Adverse Effects at 4 Weeks | Breathlessness | 0.22 Proportion of participants |
| Total Number of Patients Allocated to Study Arms | Types of Adverse Effects at 4 Weeks | Heartburn | 0.20 Proportion of participants |
| Total Number of Patients Allocated to Study Arms | Types of Adverse Effects at 4 Weeks | Abdominal pain | 0.14 Proportion of participants |
| Total Number of Patients Allocated to Study Arms | Types of Adverse Effects at 4 Weeks | Vomiting | 0.08 Proportion of participants |
| Total Number of Patients Allocated to Study Arms | Types of Adverse Effects at 4 Weeks | Diarrhea | 0.14 Proportion of participants |