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Comparison of NovaFerrum® vs Ferrous Sulfate Treatment in Young Children With Nutritional Iron Deficiency Anemia (BESTIRON)

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ClinicalTrials.gov Identifier: NCT01904864
Recruitment Status : Completed
First Posted : July 22, 2013
Results First Posted : September 13, 2017
Last Update Posted : December 14, 2017
Information provided by (Responsible Party):

Study Description
Brief Summary:

This study is a randomized, controlled, double-blinded single center trial to compare the efficacy of NovaFerrum® to ferrous sulfate for the treatment of nutritional iron deficiency anemia (IDA) in infants and young children.

Hypothesis: NovaFerrum® has greater efficacy than ferrous sulfate in increasing hemoglobin concentration during a twelve week course of treatment to subjects with iron deficiency anemia.

Primary Aim:

To compare the efficacy of NovaFerrum® to ferrous sulfate for the treatment of nutritional IDA in infants and young children as determined by increase in hemoglobin concentration.

Secondary Aims:

  1. To compare the adverse effects of treatment for IDA between ferrous sulfate and NovaFerrum®
  2. To compare normalization of iron stores as demonstrated by laboratory measures of IDA (ferritin, TIBC, reticulocyte hemoglobin content) between subjects treated with ferrous sulfate or NovaFerrum®
  3. To compare the adherence to study medication between subjects on ferrous sulfate and NovaFerrum®
  4. To demonstrate efficacy of a once daily dosing regimen in the treatment of nutritional IDA

Condition or disease Intervention/treatment Phase
Iron Deficiency Anemia Drug: elemental iron (NovaFerrum®) Drug: elemental iron (Ferrous Sulfate) Phase 4

Detailed Description:

Screening/Baseline Assessment (Week 0):

  • History and Physical Examination:
  • Detailed history regarding medical disorders predisposing to iron deficiency and diet (breast feeding, iron fortified formula, cow's milk), including total daily amount.
  • Review of existing medical records (including blood counts and iron studies) submitted by primary care provider or recorded on Children's electronic medical record.
  • History of pica and/or other sequelae from iron deficiency.
  • Details regarding prior or current iron oral therapy (dose, preparation, timing, response) or recent blood transfusions.
  • Comprehensive physical exam (PE) (baseline visit) consisting of vital signs, general, HEENT, cardio-respiratory, abdominal, extremities and skin; Focused PE (Weeks 4 and 12) consisting of vital signs, general, cardio-respiratory, abdominal and skin.
  • Laboratory (Only #3 below for research only, not standard of care):

    1. Complete blood count (CBC), reticulocyte count and reticulocyte hemoglobin content.
    2. Serum ferritin, iron and total body iron capacity (TIBC).

Treatment Interventions:

  • Patients who meet eligibility criteria and whose parents provide written informed consent will be randomized in a 1:1 ratio to receive either ferrous sulfate drops (15 mg/ml) or NovaFerrum® drops (15 mg/ml).
  • Subjects will be assigned to receive a single daily dose of 3 mg/kg elemental iron. Timing of study drug will be at bedtime.
  • As a part of standard care, patients will be advised to reduce cow milk intake to a maximum 16 oz. daily and not to give any milk after medication administration. There will be no other dietary modification prescribed by the study.
  • Other iron containing medications (including vitamins) will be discontinued.
  • Families will be asked to make a daily diary entry documenting administration and adverse effects and return the diary at follow-up clinic visits.

Follow-up Phone Contact (Weeks 2, 6, 10 - not standard of care)

- Phone contact with parents will be made biweekly between scheduled visits (e.g. Weeks 2, 6, and 10) to assess adverse effects, promote strict adherence and remind them of the next scheduled visit.

Assessment During Follow-up Visits at Weeks 4, 8, and 12 after Initiation of Therapy (Follow-up visits during weeks 4 and 12 are standard of care; Follow-up visit at week 8 is for research only):

  • Review of interval history and diet by direct questioning of the parents and review of diary regarding adherence, adverse effects of iron therapy (e.g., refusal to take, spitting/vomiting, abdominal pain, constipation, black stools, stained teeth). The diary will also contain distracter items to assess background "noise".
  • Recording of other medications or intercurrent illnesses.
  • Laboratory studies at each follow-up visit: CBC with red blood cell (RBC) indices, (MCV, RDW) reticulocyte count, reticulocyte hemoglobin content, serum ferritin, serum iron and total iron binding capacity.
  • Blood lead measurement at week 4 (research only). Will repeated only if abnormal.
  • Focused physical exam at 4 and 12 week visits

Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Single-center, Double-blinded, Randomized, 12 Week, Superiority Study in Infants and Young Children to Compare the Efficacy of NovaFerrum® Versus Ferrous Sulfate in the Treatment of Nutritional Iron Deficiency Anemia.
Study Start Date : July 2013
Primary Completion Date : November 2015
Study Completion Date : November 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Anemia Iron
U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Active Comparator: NovaFerrum®
Subjects randomized to this arm will receive a single daily dose (3mg/kg) of a 15 mg/ml elemental iron preparation, NovaFerrum®, for 12 weeks.
Drug: elemental iron (NovaFerrum®)
single daily dose (3mg/kg) of a 15 mg/ml elemental iron preparation, NovaFerrum®, for 12 weeks
Other Name: Generic Name: polysaccharide iron vitamin mineral complex
Active Comparator: Ferrous Sulfate
Subjects randomized to this arm will receive a single daily dose (3mg/kg) of a 15 mg/ml elemental iron preparation, ferrous sulfate, for 12 weeks.
Drug: elemental iron (Ferrous Sulfate)
single daily dose (3mg/kg) of a 15 mg/ml elemental iron preparation, Ferrous Sulfate, for 12 weeks
Other Name: Ferrous Sulfate

Outcome Measures

Primary Outcome Measures :
  1. Hemoglobin Concentration Over Time [ Time Frame: 12 weeks ]
    The primary outcome will be the change in the peripheral blood hemoglobin concentration in grams/deciliter upon serial measurements at 0, 4, 8, and 12 weeks post-initiation of treatment. The primary analysis consists of a linear mixed regression model, which incorporates all subsequent time points into the model and includes treatment and time as covariates and patient random effects to account for correlation among longitudinal measurements from the same patients.

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   9 Months to 48 Months   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Age ≥ 9 to < 48 months
  2. IDA documented by hematologic indices (hemoglobin, MCV, RDW, reticulocyte count, reticulocyte hemoglobin content), serum ferritin, serum iron and total iron binding capacity

Exclusion Criteria:

  1. Iron deficiency likely or definitely due to blood loss from the intestine or other sites.
  2. Evidence of response to recent/current oral iron therapy, as determined by increase in hemoglobin by > 1.0 gm/dL and MCV by 5 fL above measurements prior to iron therapy
  3. History or evidence of intestinal malabsorption
  4. History of prior intravenous iron therapy
  5. Major co-morbidity such as a serious chronic medical condition unrelated to iron deficiency apparent on history, physical examination, or laboratory tests
  6. Other causes of anemia (sickle cell disease, thalassemia, other hemolytic anemia, bone marrow failure, etc.) apparent by history, physical examination, and/or laboratory tests.
  7. High likelihood of suboptimal adherence by parents with study requirements (previous missed clinic visits)
  8. Inability to tolerate oral medications
  9. History of birth at < 30 weeks gestation
  10. Other medical or social factors at discretion of treating physician
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01904864

United States, Texas
Children's Medical Center Dallas
Dallas, Texas, United States, 75235
Sponsors and Collaborators
University of Texas Southwestern Medical Center
Gensavis Pharmaceuticals, LLC
Principal Investigator: Patrick Leavey, MD U Texas Southwestern
More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Patrick Leavey, Professor, University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier: NCT01904864     History of Changes
Other Study ID Numbers: FE15929
First Posted: July 22, 2013    Key Record Dates
Results First Posted: September 13, 2017
Last Update Posted: December 14, 2017
Last Verified: November 2017

Keywords provided by Patrick Leavey, University of Texas Southwestern Medical Center:
randomized controlled trial
iron medication
Hematologic Disease
Anemia, Iron deficiency
anemia, nutritional
ferrous sulfate

Additional relevant MeSH terms:
Anemia, Iron-Deficiency
Deficiency Diseases
Hematologic Diseases
Anemia, Hypochromic
Iron Metabolism Disorders
Metabolic Diseases
Nutrition Disorders
Trace Elements
Growth Substances
Physiological Effects of Drugs