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

Iron-Deficiency Anemia Clinical Trial

— Ferinject  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02541708
• Other study ID #: IFCIDA 001-2015
• Status: Active, not recruiting
• Phase: Phase 3
• First received: August 12, 2015
• Last updated: April 22, 2017
• Start date: September 2015
• Est. completion date: April 2018

Study information

• Verified date: April 2017
• Source: Ifakara Health Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 230
• Est. completion date: April 2018
• Est. primary completion date: April 2018
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 49 Years

Eligibility

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.

Related Conditions & MeSH terms

• Anemia
• Anemia, Iron-Deficiency
• Deficiency Diseases
• Iron-Deficiency Anemia

Intervention

Drug:
• Ferric carboxymaltose
Intravenous Ferric carboxymaltose given at a calculated dose of 20mg/kg body weight in 1-3 infusions according to severity of anemia
• Ferrous sulfate + folic acid
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

Locations

Country	Name	City	State
Tanzania	Ifakara Health Institute	Bagamoyo

Sponsors (2)

Lead Sponsor	Collaborator
Ifakara Health Institute	Swiss Tropical & Public Health Institute

Country where clinical trial is conducted

Tanzania, 

References & Publications (10)

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. — View Citation

Beard JL, Hendricks MK, Perez EM, Murray-Kolb LE, Berg A, Vernon-Feagans L, Irlam J, Isaacs W, Sive A, Tomlinson M. Maternal iron deficiency anemia affects postpartum emotions and cognition. J Nutr. 2005 Feb;135(2):267-72. — View 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. — View 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. Review. — View Citation

Moore RA, Gaskell H, Rose P, Allan J. Meta-analysis of efficacy and safety of intravenous ferric carboxymaltose (Ferinject) from clinical trial reports and published trial data. BMC Blood Disord. 2011 Sep 24;11:4. doi: 10.1186/1471-2326-11-4. — View Citation

Rohner F, Zimmermann MB, Amon RJ, Vounatsou P, Tschannen AB, N'goran EK, Nindjin C, Cacou MC, Té-Bonlé 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. — View Citation

van Hensbroek MB, Jonker F, Bates I. Severe acquired anaemia in Africa: new concepts. Br J Haematol. 2011 Sep;154(6):690-5. doi: 10.1111/j.1365-2141.2011.08761.x. Epub 2011 Jun 28. Review. — View Citation

Van Wyck DB, Mangione A, Morrison J, Hadley PE, Jehle JA, Goodnough LT. Large-dose intravenous ferric carboxymaltose injection for iron deficiency anemia in heavy uterine bleeding: a randomized, controlled trial. Transfusion. 2009 Dec;49(12):2719-28. doi: 10.1111/j.1537-2995.2009.02327.x. Epub 2009 Jul 22. — View Citation

Van Wyck DB, Martens MG, Seid MH, Baker JB, Mangione A. Intravenous ferric carboxymaltose compared with oral iron in the treatment of postpartum anemia: a randomized controlled trial. Obstet Gynecol. 2007 Aug;110(2 Pt 1):267-78. Erratum in: Obstet Gynecol. 2008 Apr;111(4):996. — View Citation

Zimmermann MB, Chassard C, Rohner F, N'goran EK, Nindjin C, Dostal A, Utzinger J, Ghattas H, Lacroix C, Hurrell RF. The effects of iron fortification on the gut microbiota in African children: a randomized controlled trial in Cote d'Ivoire. Am J Clin Nutr. 2010 Dec;92(6):1406-15. doi: 10.3945/ajcn.110.004564. Epub 2010 Oct 20. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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)	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.	1 year
Other	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)	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.	1 year
Other	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)	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.	1 year
Other	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)	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.	1 year
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

External Links

•   Ifakara Health Institute
•   National Institute for Medical Research
•   Swiss Tropical and Public Health Institute
•   Tanzania Food and Drugs Authority