Daily vs Intermittent Iron Therapy in Pregnancy

Study Overview
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Brief Summary
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This is a randomized non inferiority trial to evaluate the response to iron therapy in the standard daily vs. intermittent (three-four times a week on nonconsecutive days) groups by using hematological markers (hemoglobin, hematocrit, transferrin, hepcidin, ferritin, human soluble transferrin receptor). The secondary outcome is to evaluate gastrointestinal discomfort and adherence to therapy between two treatment groups.

Detailed Description
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The Centers for Disease Control and Prevention estimates that as many as 8 million American women of childbearing age are iron deficient. In a typical singleton gestation, the maternal need for iron averages close to 1000 mg. Of this 300 mg is for the fetus and placenta; 500 mg for maternal hemoglobin mass expansion; and 200 mg that is normally shed through the gut, urine, and skin. The total amount of 1000 mg considerably exceeds the iron stores of most women and results in iron-deficiency anemia unless iron supplementation is given. Correction of anemia and restitution of iron stores can be accomplished with simple iron compounds-ferrous sulfate, fumarate or gluconate. Oral iron is an effective treatment for iron deficiency anemia and is inexpensive, safe and widely available. In the past, a standard approach to the treatment of iron deficiency anemia was oral ferrous sulfate 325 mg (65 mg elemental iron) spaced in 3 doses each day for a total daily dose of 195 mg elemental iron. However, recent absorption studies concluded that maximal absorption of iron occurs with a dose in the range of 40 to 80 mg of elemental iron daily. This study was done in non pregnant iron-deficient women. Greater doses do not result in more iron absorption and are associated with more side effects. The findings of this study have been implemented by many into various areas of medicine. Daily oral supplementation in pregnant women has been a long-standing, cost-effective recommended intervention both in the public health and clinical fields. However, adherence to daily iron and folic acid supplementation still faces challenges. Data from national surveys from 46 countries (2003 to 2009) indicate that about 52% to 75% of mothers receive any iron tablets during pregnancy, and the duration of supplementation is usually short. According to a study by Khalafallah, the side effects or oral iron therapy including gastrointestinal disturbances characterized by colicky pain, nausea, vomiting, diarrhea, and constipation occur in about 50% of a patient taking iron preparations, and the investigators estimate that their patients have similar complaints and intolerances. Many pregnant women taking oral iron, especially at doses greater than 30 mg daily of elemental iron daily, have gastrointestinal side effects, which cause them to discontinue the iron therapy. Taking iron supplementation on an intermittent basis may help to reduce gastrointestinal side effects and improve iron stores. In the United States, the oral iron preparation of ferrous sulfate is often used to replete iron-deficient women. To the investigators' knowledge, studies have not been performed to evaluate daily vs. oral intermittent oral iron therapy in the United States, which has a different nutritional status and access to health care than other countries. This study will randomize patients to the standard therapy: taking iron ferrous sulfate 325 mg (daily) by mouth once a day by mouth or intermittent therapy of taking ferrous sulfate 325 mg three- four times a week on alternating days. Hematological markers (hemoglobin, hematocrit, transferrin, hepcidin, ferritin, human soluble transferrin receptor), will be assessed prior to treatment and after treatment is completed.

Official Title
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Daily vs. Intermittent Iron Therapy in Iron Deficient Pregnant Patients: A Randomized Noninferiority Trial

Conditions
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Iron Deficiency Anemia of Pregnancy

Intervention / Treatment
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* Dietary Supplement: Ferrous Sulfate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pregnant women who are not underweight (BMI < 18.5 kg/m2) Reproductive-aged women 18-50 Singleton Pregnancy. Patients undergoing third trimester blood work from 26-28 weeks. Women who have had previously normal first-trimester blood work (hemoglobin, hematocrit, MCV) without any evidence of existing anemia. Pregnant women with anemia designated with hemoglobin concentration less than 11 g/dL or hematocrit less than 33% No pre-existing iron deficiency anemia or not already on iron supplementation. Exclusion Criteria: Women with medical problems known to affect iron metabolism or homeostasis Women with existing thalassemias or anemias. Women with abnormal bloodwork indicating anemia earlier in the pregnancy. Women are already taking iron supplementation during the pregnancy for treatment of iron deficiency anemia. Chronic illness is influencing iron absorption. Underlying malabsorption disease. History of bariatric surgery. Severe anemia with maternal hemoglobin levels less than 6 g/dL Preterm Labor, PPROM, signs of infection.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized Noninferiority Trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Daily<br>Patients randomized to this arm will take ferrous sulfate 325 mg every day. | Dietary Supplement: Ferrous Sulfate<br>* Patients would be randomized to either taking ferrous sulfate daily or every other day (on non consecutive days).<br>|
| Other: Intermittent (Every other day)<br>Patient's randomized to this arm will take ferrous sulfate 325 mg every other day. | Dietary Supplement: Ferrous Sulfate<br>* Patients would be randomized to either taking ferrous sulfate daily or every other day (on non consecutive days).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hematologic values assessed for anemia | Hematologic values of hemoglobin, hematocrit, transferrin, hepcidin, human soluble transferrin receptor and ferritin. | This will be measured 4-6 weeks after starting treatment. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Scores on self report survey of gastrointestinal adverse side effects after oral iron supplementation | The study adapts a previously validated questionnaire to capture side effects normally associated with oral iron supplementation. A likert scale is used with intermediate anchors to quantify side effects as absent, mild, moderate or severe. Absent was 0 symptoms experienced. Mild was less than 3 times a week, moderate was 3-5 times a week and severe was every single day. The possible total score is 60 with higher numbers representing more severe symptoms. These numbers will be compared between the two treatment groups. | Side effects will be reviewed every 2 weeks for a period of 4-6 weeks. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Iron Deficiency Anemia, Pregnancy, Side Effects