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

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

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