IV Ferric Carboxymaltose Compared With Oral Iron in the Treatment of Iron Deficiency Anemia at Delivery in Tanzania

Study Overview
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Brief Summary
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Intravenous iron preparations have been shown to be superior to oral iron and have largely replaced the treatment of anaemia in Northern countries. However, the socio-economic and medical conditions in low resource countries greatly differ from those in northern countries. Patients' different access to medication supply, perception of medication need and compliance as well as the burden of concomitant disease like malaria, soil-transmitted helminths, schistosomiasis, HIV and red blood cells (RBC) genetic disorders may influence effectiveness and safety of iron substitution modality. The aim of the present study is to compare iv iron substitution by ferric carboxymaltose (Ferinject®) to per oral iron substitution in a low resource country

Detailed Description
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The objectives of the study are as follows: Primary objective: To assess the superiority in terms of effectiveness of iv iron substitution with ferric carboxymaltose versus per oral iron substitution in women with iron deficient anemia at delivery in Tanzania. Secondary objectives To evaluate safety and feasibility of intravenous ferric carboxymaltose substitution compared to per oral iron substitution in a resource limited country To evaluate acceptance of intravenous ferric carboxymaltose substitution compared to per oral iron substitution in a resource limited country To evaluate wellbeing of women receiving intravenous ferric carboxymaltose compared to women receiving per oral iron substitution To evaluate the sensitivity of diagnosis of iron deficiency by measuring hemoglobin, mean corpuscular volume (MCV) and mean corpuscular hemoglobin concentration (MCHC) only, compared to the diagnosis by measuring iron metabolism parameters in a resource limited country

Official Title
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Intravenous Ferric Carboxymaltose Compared With Oral Iron in the Treatment of Iron Deficiency Anemia at Delivery in Tanzania

Conditions
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Iron-Deficiency Anemia

Intervention / Treatment
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* Drug: Ferric carboxymaltose
* Drug: Ferrous sulfate + folic acid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women close to delivery Screening will be performed using the HemoCue System. In case of anemia, defined by Hg <110 g/l, a venous puncture will be performed and the blood analyzed on a 5 population analyzer with erythrocyte indices and Reticulocyte indices and ferritin determined. Then If the anemia defined as Hg <110 g/l is confirmed and the if ferritin is below 50 ng/ml, the patient will be included in the present study Patient compliance and geographic proximity allow proper staging and follow-up Patient must give written informed consent before registration Exclusion Criteria: Active malaria; patients will be tested for malaria by Rapid Diagnostic Test and microscopy and if positive treated. Patient with treated malaria can be included Helminthic infection; patients will be tested for helminthic infections by a stool ova and parasite exam and if positive treated by single oral dose of 400 mg albendazole. Treated patients can be included. HIV positivity. Patients will be tested and if positive they will be referred to the Care and Treatment Clinic at Bagamoyo District Hospital and excluded from the study. Known hemoglobinopathy C-Reactive protein (CRP) >20 Patients with chronic fever Psychiatric disorder precluding understanding of information on trial related topics or giving informed consent Concurrent treatment with other experimental drugs or treatment in another clinical trial within 30 days prior to trial entry Any serious underlying medical condition (at the judgment of the investigator) which could impair the ability of the patient to participate in the trial Known allergy or hypersensitivity to study drug.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 49 Years

Sexes Eligible for Study
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Female

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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IV ferric carboxymaltose<br>IV Ferric carboxymaltose is given at a dose calculated according to the severity of anemia and patients weight. The maximal weekly dose is 1000mg. If total dose exceeds 1000mg the dose is split in 1-3 infusions with one infusion per week. | Drug: Ferric carboxymaltose<br>* Intravenous Ferric carboxymaltose given at a calculated dose of 20mg/kg body weight in 1-3 infusions according to severity of anemia<br>* Other names: Ferinject;|
| Active Comparator: Ferrous sulphate 60mg+Folic acid 0.25mg<br>Three dried ferrous sulphate and folic acid tablets every morning 30 mins before the meal. If side effects occur the drug may be taken with the meal or in 2 separate doses per day. The treatment will be pursued for 3 months after correction of anemia. | Drug: Ferrous sulfate + folic acid<br>* Three dried ferrous sulfate and folic acid tablets every morning 30 mins before the meal. If side effects occur the drug may be taken with the meal or in 2 separate doses per day. The treatment will be pursued for 3 months after correction of anemia<br>* Other names: Fefo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of women with correction of hemoglobin to normal values (Hb> 11.5g/dl) at 6 weeks by treatment arm | The proportion of women in each trial arm who have attained the corrected hemoglobin to normal values after starting trial treatment. | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best response (Hemoglobin) in grams per decilitre (g/dl) | Is the highest hemoglobin value or maximal hemoglobin increase after start of study medication | up to 1 year | 
| Percentage of women with corrected iron deficiency (Ferritin>50ng/ml) in each arm | The proportion of women in each trial arm who have attained the corrected serum ferritin levels to normal values after starting trial treatment in nanograms per milliltre(ng/mL) | 6 weeks | 
| Best response (Ferritin) in nanograms per milliltre (ng/mL) | Is the highest ferritin value or maximal ferritin increase after start of study medication. The proportion of women in each trial arm who have attained the corrected serum ferritin levels to normal values after starting trial treatment | up to 1 year | 
| Time to response (Hemoglobin) in weeks | Is the time interval between the date of start of study medication until the date of reaching maximal hemoglobin value | up to 1 year | 
| Time to response (Ferritin) in weeks | Is the time interval between the date of start of study medication until the date of reaching maximal ferritin value | up to 1 year | 
| Response duration (Hemoglobin) in weeks | Is the time from the date when the highest hemoglobin value is reached until the date of decrease to Hb<11.5 g/dl or a decrease of more than 1 g/dl | up to 1 year | 
| Response duration (Ferritin) in weeks | Is the time from the date when the highest ferritin value is reached until the date of decrease to ferritin<50 ng/ml | up to 1 year | 
| Frequency and severity of solicited and non-solicited adverse events after IV ferric carboxymaltose substitution and oral iron substitution | Number of participants with adverse events either clinical events or abnormal laboratory values with grading of severity reported according to the Common Terminology Criteria of Adverse Events (CTCAE) version 4 | up to 1 year | 
| Compliance to study medication intake after intravenous ferric carboxymaltose substitution and oral iron substitution (Questionnaire and pill count) | The proportion of women in each trial arm who have completed the trial related treatment either the number of prescribed infusions of ferric carboxymaltose or oral tablets of ferrous sulphate and folic acid | up to 1 year |