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

Primary Purpose

Iron-Deficiency Anemia

Status
Unknown status
Phase
Phase 3
Locations
Tanzania
Study Type
Interventional
Intervention
Ferric carboxymaltose
Ferrous sulfate + folic acid
Sponsored by
Ifakara Health Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Iron-Deficiency Anemia

Eligibility Criteria

18 Years - 49 Years (Adult)FemaleDoes not accept healthy volunteers

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.

Sites / Locations

  • Ifakara Health Institute

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

IV ferric carboxymaltose

Ferrous sulphate 60mg+Folic acid 0.25mg

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Best response (Hemoglobin) in grams per decilitre (g/dl)
Is the highest hemoglobin value or maximal hemoglobin increase after start of study medication
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)
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
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
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
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
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
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
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

Full Information

First Posted
August 12, 2015
Last Updated
April 22, 2017
Sponsor
Ifakara Health Institute
Collaborators
Swiss Tropical & Public Health Institute
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1. Study Identification

Unique Protocol Identification Number
NCT02541708
Brief Title
IV Ferric Carboxymaltose Compared With Oral Iron in the Treatment of Iron Deficiency Anemia at Delivery in Tanzania
Acronym
Ferinject
Official Title
Intravenous Ferric Carboxymaltose Compared With Oral Iron in the Treatment of Iron Deficiency Anemia at Delivery in Tanzania
Study Type
Interventional

2. Study Status

Record Verification Date
April 2017
Overall Recruitment Status
Unknown status
Study Start Date
September 2015 (undefined)
Primary Completion Date
April 2018 (Anticipated)
Study Completion Date
April 2018 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ifakara Health Institute
Collaborators
Swiss Tropical & Public Health Institute

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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
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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Iron-Deficiency Anemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
230 (Actual)

8. Arms, Groups, and Interventions

Arm Title
IV ferric carboxymaltose
Arm Type
Experimental
Arm Description
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.
Arm Title
Ferrous sulphate 60mg+Folic acid 0.25mg
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Ferric carboxymaltose
Other Intervention Name(s)
Ferinject
Intervention Description
Intravenous Ferric carboxymaltose given at a calculated dose of 20mg/kg body weight in 1-3 infusions according to severity of anemia
Intervention Type
Drug
Intervention Name(s)
Ferrous sulfate + folic acid
Other Intervention Name(s)
Fefo
Intervention Description
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
Primary Outcome Measure Information:
Title
Percentage of women with correction of hemoglobin to normal values (Hb> 11.5g/dl) at 6 weeks by treatment arm
Description
The proportion of women in each trial arm who have attained the corrected hemoglobin to normal values after starting trial treatment.
Time Frame
6 weeks
Secondary Outcome Measure Information:
Title
Best response (Hemoglobin) in grams per decilitre (g/dl)
Description
Is the highest hemoglobin value or maximal hemoglobin increase after start of study medication
Time Frame
up to 1 year
Title
Percentage of women with corrected iron deficiency (Ferritin>50ng/ml) in each arm
Description
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)
Time Frame
6 weeks
Title
Best response (Ferritin) in nanograms per milliltre (ng/mL)
Description
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
Time Frame
up to 1 year
Title
Time to response (Hemoglobin) in weeks
Description
Is the time interval between the date of start of study medication until the date of reaching maximal hemoglobin value
Time Frame
up to 1 year
Title
Time to response (Ferritin) in weeks
Description
Is the time interval between the date of start of study medication until the date of reaching maximal ferritin value
Time Frame
up to 1 year
Title
Response duration (Hemoglobin) in weeks
Description
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
Time Frame
up to 1 year
Title
Response duration (Ferritin) in weeks
Description
Is the time from the date when the highest ferritin value is reached until the date of decrease to ferritin<50 ng/ml
Time Frame
up to 1 year
Title
Frequency and severity of solicited and non-solicited adverse events after IV ferric carboxymaltose substitution and oral iron substitution
Description
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
Time Frame
up to 1 year
Title
Compliance to study medication intake after intravenous ferric carboxymaltose substitution and oral iron substitution (Questionnaire and pill count)
Description
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
Time Frame
up to 1 year
Other Pre-specified Outcome Measures:
Title
Sensitivity of erythrocyte indices for the diagnosis of iron deficiency anemia in Tanzania (parameters used are mean corpuscular volume(MCV) and mean corpuscular hemoglobin concentration(MCHC)
Description
Is the probability that a test (erythrocyte indices) will indicate iron deficiency among participants with the disease as confirmed by iron metabolism parameters (Gold standard). It will be reported as percentage.
Time Frame
1 year
Title
Specificity of erythrocyte indices for the diagnosis of iron deficiency anemia in Tanzania ((parameters used are mean corpuscular volume(MCV) and mean corpuscular hemoglobin concentration(MCHC)
Description
Is the fraction of those without disease (iron deficiency) confirmed by iron metabolism parameters who will have a negative test (erythrocyte indices) results. It will be reported as percentage.
Time Frame
1 year
Title
Positive predictive value of erythrocyte indices for the diagnosis of iron deficiency anemia in Tanzania (parameters used are mean corpuscular volume(MCV) and mean corpuscular hemoglobin concentration(MCHC)
Description
Is the proportion of participants who truly have the disease(iron deficiency) as confirmed by iron metabolism parameters among the total number of participants with positive test results(erythrocyte indices). It will be reported as percentage.
Time Frame
1 year
Title
Negative predictive value of erythrocyte indices for the diagnosis of iron deficiency anemia in Tanzania (parameters used are mean corpuscular volume(MCV) and mean corpuscular hemoglobin concentration(MCHC)
Description
Is the proportion of participants who do not have the disease(iron deficiency) as confirmed by iron metabolism parameters among the total number of participants with negative test results(erythrocyte indices). It will be reported as percentage.
Time Frame
1 year

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
49 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sandrine Meyer-Monard, PD DrMed
Organizational Affiliation
Swiss Tropical & Public Health Institute
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Salim Abdulla, MD,PhD
Organizational Affiliation
Ifakara Health Institute
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Marcel Tanner, PhD, MPH
Organizational Affiliation
Swiss Tropical & Public Health Institute
Official's Role
Study Chair
Facility Information:
Facility Name
Ifakara Health Institute
City
Bagamoyo
ZIP/Postal Code
74
Country
Tanzania

12. IPD Sharing Statement

Citations:
PubMed Identifier
21707575
Citation
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Results Reference
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21813172
Citation
Balarajan Y, Ramakrishnan U, Ozaltin E, Shankar AH, Subramanian SV. Anaemia in low-income and middle-income countries. Lancet. 2011 Dec 17;378(9809):2123-35. doi: 10.1016/S0140-6736(10)62304-5. Epub 2011 Aug 1.
Results Reference
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PubMed Identifier
11518906
Citation
Bodnar LM, Scanlon KS, Freedman DS, Siega-Riz AM, Cogswell ME. High prevalence of postpartum anemia among low-income women in the United States. Am J Obstet Gynecol. 2001 Aug;185(2):438-43. doi: 10.1067/mob.2001.115996.
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Citation
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Results Reference
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PubMed Identifier
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Citation
Lynch SR. Why nutritional iron deficiency persists as a worldwide problem. J Nutr. 2011 Apr 1;141(4):763S-768S. doi: 10.3945/jn.110.130609. Epub 2011 Mar 2.
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Rohner F, Zimmermann MB, Amon RJ, Vounatsou P, Tschannen AB, N'goran EK, Nindjin C, Cacou MC, Te-Bonle MD, Aka H, Sess DE, Utzinger J, Hurrell RF. In a randomized controlled trial of iron fortification, anthelmintic treatment, and intermittent preventive treatment of malaria for anemia control in Ivorian children, only anthelmintic treatment shows modest benefit. J Nutr. 2010 Mar;140(3):635-41. doi: 10.3945/jn.109.114256. Epub 2010 Jan 27.
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derived
Links:
URL
http://www.tfda.or.tz
Description
Tanzania Food and Drugs Authority
URL
http://www.swisstph.ch
Description
Swiss Tropical and Public Health Institute
URL
http://www.ihi.or.tz
Description
Ifakara Health Institute
URL
http://www.nimr.or.tz
Description
National Institute for Medical Research

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

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