Daily vs Alternate Day Iron Supplementation for Pregnant Women With Iron Deficiency Anemia

Sponsor

Icahn School of Medicine at Mount Sinai (Other)

Overall Status

Completed

CT.gov ID

NCT03562143

Collaborator

(none)

Enrollment

Location

Arms

17.7

Actual Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Iron deficiency is thought to be the most common nutrient deficiency among pregnant women and the most common cause of anemia in pregnancy. The consequences of iron deficiency anemia are serious and can include diminished intellectual and productive capacity and possibly increased susceptibility to infection in mothers and infants, low birthweight, and premature births, hence the importance of appropriate treatment during pregnancy.

Most guidelines recommend an increase in iron consumption by about 15-30 mg/day, an amount readily met by most prenatal vitamin formulations. This is adequate supplementation for non-anemic and non-iron-deficient women. However, women with iron deficiency anemia should receive an additional 30-20 mg/day until the anemia is corrected.

It is not clear whether intermittent administration of oral iron is equivalent to once daily to rise the hemoglobin levels in pregnant women with iron deficiency anemia. Alternate day treatment with supplemental iron has been suggested as a way to improve its absorption because daily doses may suppress the mucosal uptake of iron even in the presence of iron deficiency until the intestinal mucosa completes its turnover.

Another possible factor associated with the frequency of iron dosing is related to hepcidin, the central regulatory molecule in the metabolism of iron in mammals. The synthesis of hepcidin is controlled by 3 kinds of signals: inflammation; the need for increased erythropoiesis, and an iron status signal based on plasma iron levels and iron stores. If plasma iron levels or iron stores are increased, the resulting signal increases hepcidin levels, thereby blocking iron absorption and its release from stores (liver, macrophages) and preventing iron overload.This hepcidin effect, suppressing iron absorption, could last as long as 48h.

In this study, the researchers aim to determine if alternate day dosing of iron in pregnant women with iron deficiency anemia results in improved levels of hemoglobin or hematocrit and ferritin.

Hepcidin levels will be compared between patients on daily iron supplementation versus alternate day supplementation.

The researchers will also evaluate if alternate day dosing of iron supplementation results in a better side effect profile, and with better patient compliance.

Condition or Disease	Intervention/Treatment	Phase
Iron Deficiency Anemia	Dietary Supplement: Ferrous Sulfate Dietary Supplement: Ferrous Sulfate	N/A

Study Design

Study Type:

Interventional

Actual Enrollment :

88 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Patients that agree to participate will be randomized to receive either 1 tablet of 325mg ferrous sulfate (65 mg of elemental iron) on consecutive days for 6 weeks or 2 tablets together (130 mg of elemental iron ) every other day for 6 weeks. Both groups will be receiving the same total amount of iron over the study period (2730 mg of elemental iron over 6 weeks).Patients that agree to participate will be randomized to receive either 1 tablet of 325mg ferrous sulfate (65 mg of elemental iron) on consecutive days for 6 weeks or 2 tablets together (130 mg of elemental iron ) every other day for 6 weeks. Both groups will be receiving the same total amount of iron over the study period (2730 mg of elemental iron over 6 weeks).

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Daily vs Alternate Day Iron Supplementation for Pregnant Women With Iron Deficiency Anemia: A Randomized Controlled

Actual Study Start Date :

Aug 31, 2018

Actual Primary Completion Date :

Feb 20, 2020

Actual Study Completion Date :

Feb 20, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Alternate-day iron supplementation Patients taking iron supplementation given as 2 tabs of 325 mg ferrous sulfate (equivalent to 130 mg of elemental iron) for 6 weeks.	Dietary Supplement: Ferrous Sulfate Patients will take iron supplementation given as 2 tabs of 325 mg ferrous sulfate (equivalent to 130 mg of elemental iron) on alternate day for 6 weeks. Other Names: Alternate-day iron supplementation
Active Comparator: Daily iron supplementation Patients taking iron supplementation given as 1 tab of 325 mg ferrous sulfate (equivalent to 65 mg of elemental iron) for 6 weeks.	Dietary Supplement: Ferrous Sulfate Patients will take iron supplementation given as 1 tab of 325 mg ferrous sulfate (equivalent to 65 mg of elemental iron) daily for 6 weeks. Other Names: Daily iron supplementation

Arm

Intervention/Treatment

Experimental: Alternate-day iron supplementation

Patients taking iron supplementation given as 2 tabs of 325 mg ferrous sulfate (equivalent to 130 mg of elemental iron) for 6 weeks.

Dietary Supplement: Ferrous Sulfate

Patients will take iron supplementation given as 2 tabs of 325 mg ferrous sulfate (equivalent to 130 mg of elemental iron) on alternate day for 6 weeks.

Other Names:

Alternate-day iron supplementation

Active Comparator: Daily iron supplementation

Patients taking iron supplementation given as 1 tab of 325 mg ferrous sulfate (equivalent to 65 mg of elemental iron) for 6 weeks.

Dietary Supplement: Ferrous Sulfate

Patients will take iron supplementation given as 1 tab of 325 mg ferrous sulfate (equivalent to 65 mg of elemental iron) daily for 6 weeks.

Other Names:

Daily iron supplementation

Outcome Measures

Primary Outcome Measures

Change in Hemoglobin Level [baseline and 6 weeks]
The change in the level of hemoglobin in pregnant patients with iron deficiency anemia after 6 weeks of treatment with either daily or alternate-day iron supplementation.

Secondary Outcome Measures

Change in Ferritin Level [baseline and 6 weeks]
Change in the level of ferritin in pregnant patients with iron deficiency anemia after 6 weeks of treatment with either daily or alternate-day iron supplementation.
Change in Fasting Hepcidin Level [Baseline and Day 43 post treatment]
At the end of the 6 weeks of treatment, hepcidin levels will be obtained on day 43 of the study. The 6-week hepcidin level will be compared to the starting hepcidin which will be drawn prior to initiating iron supplementation.
Side effects from Iron Supplementation Questionnaire [6 weeks]
Patients will be asked to fill a questionnaire after 6 weeks to assess for adverse symptoms associated with consumption of iron including constipation, nausea, vomiting, diarrhea, abdominal pain, and headache. Each of these items is scaled from 0 (not al all) to 10 (very much), with total scale from 0-60, with higher score indicating more severe symptoms.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 64 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

Pregnant patients with iron deficiency anemia, defined as Hb less than 11.0 or hematocrit less than 33% with ferritin 25 ug/L
Age 18-64 years old.
Gestational age between 12 0/7 weeks and 34 0/7 weeks.
No other known causes of anemia (Folate or vit b12 deficiency anemia, sideroblastic anemia, thalassemia, sickle cell anemia, aplastic anemia, hemolytic anemia, anemia of chronic disease). Anemic patients with a low ferritin level and a mean corpuscular volume (MCV) >95 will have folate and vitamin B12 measured since some patients might have combined causes of anemia and might not respond as expected to iron supplementation only.

Patients will also be required to have a normal HB electrophoresis; this is a routine test obtained on all prenatal patients.

Exclusion Criteria:

Patients currently receiving iron supplementation
Malabsorptive and restrictive bariatric surgery
Inflammatory bowel disease
Irritable bowel syndrome
Celiac disease/atrophic gastritis/Helicobacter pylori
Active infection (ferritin can be falsely elevated since apoferritin is an acute-phase protein like CRP and increases both during infections and inflammatory reactions eg postoperatively).
Patients with contraindications to iron supplementation such as iron overload or hypersensitivity