Intravenous Iron for Iron-deficiency Anemia in Pregnancy: a Randomized Controlled Trial

ID: NCT03438227
Status: Not yet recruiting
Phase: Phase 4
Start Date: March 01, 2018
First Submitted: January 25, 2018
Last Updated: February 15, 2018
Results: N/A
Sponsors & Collaborators: Washington University School of Medicine
Location: United States
Conditions: Iron Deficiency Anemia of Pregnancy, Iron Malabsorption
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Study Description

Brief Summary

Iron deficiency is the most common cause of anemia in pregnancy worldwide, and, when severe, can have serious consequences for mothers and babies. While treatment of iron-deficiency anemia with iron supplementation is recommended, treatment strategies remain controversial: the American College of Obstetrics and Gynecology recommends oral iron supplementation with parental iron reserved for the rare patient who cannot tolerate or will not take oral iron, while UK professional organizations recommend a more liberal use of parenteral iron. The reason for these disparate recommendations is that few high-quality studies comparing oral to parenteral iron have been conducted in developed countries, and the potential impact of parental iron treatment on obstetric and perinatal outcomes remains unclear. We propose the first randomized-controlled trial in the United States describing the effectiveness and safety of treating pregnant women with iron-deficiency anemia with a protocol including parenteral iron compared with a protocol based on oral iron.

Detailed Description

Iron deficiency is the most common cause of anemia in pregnancy worldwide, and, when severe, can have serious consequences for mothers and babies. In the U.S., anemia affects nearly 20% of pregnancies and the majority is iron-deficiency anemia. Therefore, treatment of iron-deficiency anemia with iron supplementation is recommended.1 However, there is controversy about the treatment strategies.

The American College of Obstetrics and Gynecology recommends oral iron supplementation for iron-deficiency anemia in pregnancy, with parental iron reserved only for the "rare patient who cannot tolerate or will not take oral iron" (1) Conversely, guidelines from the U.K. are more liberal on the use of parental iron for the treatment of iron-deficiency anemia in pregnancy (2). Both treatment guidelines are based on limited data regarding the risks and benefits of parental iron for treatment of iron-deficiency anemia in pregnancy. The majority of randomized trials were conducted in developing country settings. In fact, few high-quality studies have been conducted in developed countries, and none has been conducted in the U.S. Moreover, there is limited data from prior studies on the impact of parental iron treatment on perinatal outcomes. The most recent Cochrane review including mostly from trials conducted in low-income countries found that, although parenteral iron improved hemoglobin levels and iron stores than the oral route, no clinical outcomes were assessed and there were insufficient data on adverse effects (3). The authors concluded that "large, good quality trials, assessing clinical outcomes including adverse effects … are required" (3).

This randomized controlled trial aims to assess the effectiveness and safety of treating pregnant women with iron-deficiency anemia with a protocol including parenteral iron compared with a protocol based on oral iron. We hypothesize that treating iron-deficiency anemia with parental iron is associated with improved maternal and neonatal outcomes compared with a protocol based on oral iron. To increase generalizability of the findings, we will use broad inclusion criteria and analyze data using the intention-to-treat principle.
Condition or disease Intervention/treatment Phase

Iron Deficiency Anemia of Pregnancy

Iron Malabsorption

Drug: Iron dextran
Other Names
Experimental
Drug: Ferrous sulfate 325mg
Other Names
Active comparator
Phase 4

Tracking Information

First Submitted DateJanuary 25, 2018
Last Update Posted DateFebruary 15, 2018
Anticipated Start DateMarch 01, 2018
Anticipated Completion DateAugust 01, 2019
Anticipated Primary Completion DateJune 30, 2019
Results First Submitted DateN/A
Received Results Disposit DateN/A

Current Primary Outcome Measures

  • Maternal outcome: hemoglobin on admission to inpatient obstetrics unit for delivery of infant [Time Frame: On admission to inpatient obstetrics unit for delivery of infant]

    Hemoglobin

Original Primary Outcome Measures

Not Available

Current Secondary Outcome Measures

  • Incidence of Medication Adverse events [Safety and Tolerability] [Time Frame: 2 days after after iron infusion]

    Research assistants will contact all patients receiving iron infusions 2 days after their infusion to assess for symptoms via a telephone questionnaire.

  • Maternal outcome: hemoglobin on postpartum day #1 [Time Frame: On day after participant delivered her infant (i.e. postpartum day #1)]

    Hemoglobin

  • Maternal outcome: incidence of blood transfusion [Time Frame: During inpatient admission for delivery of neonate]

    Participant receiving transfusion of packed red blood cells during admission for delivery of infant obtained via medical chart review.

  • Maternal outcome: mode of delivery [Time Frame: Once, at infant delivery]

    Whether infant was delivered vaginally or via cesarean section

  • Neonatal outcomes: gestational age at delivery [Time Frame: Once, at infant delivery]

    Gestational age at delivery

  • Neonatal outcomes: birth weight [Time Frame: Obtained once, at infant delivery]

    Infant birth weight

  • Neonatal outcomes: umblical cord gases [Time Frame: Drawn once from umbilical cord segment at birth]

    Umbilical cord gases

  • Neonatal outcomes: APGAR scores [Time Frame: Obtained at 1 minute and 5 minutes of life]

    APGAR scores. The APGAR score measures the physical condition of a newborn infant on a scale from 0 to 10 by adding points (2, 1, or 0) for heart rate, respiratory effort, muscle tone, response to stimulation, and skin color.

  • Neonatal outcomes: neonatal hemoglobin [Time Frame: Drawn once from umbilical cord segment at birth]

    Neonatal hemoglobin

  • Neonatal outcomes: neonatal morbidity composite [Time Frame: At birth]

    Neonatal morbidity composite, defined by the occurrence of one or more of the following neonatal morbidities: neonatal seizures, intraventricular hemorrhage, hypoxic-ischemic encephalopathy, neonatal hypothermic therapy, sepsis, respiratory distress syndrome, hyperbilirubinemia requiring photo therapy, birth injury, or meconium aspiration syndrome, NICU admission

Original Secondary Outcome Measures

Not Available

Study Design

Brief TitleIntravenous Iron for Iron-deficiency Anemia in Pregnancy: a Randomized Controlled Trial
Official TitleIntravenous Iron for Iron-deficiency Anemia in Pregnancy: a Randomized Controlled Trial
Brief Summary

Iron deficiency is the most common cause of anemia in pregnancy worldwide, and, when severe, can have serious consequences for mothers and babies. While treatment of iron-deficiency anemia with iron supplementation is recommended, treatment strategies remain controversial: the American College of Obstetrics and Gynecology recommends oral iron supplementation with parental iron reserved for the rare patient who cannot tolerate or will not take oral iron, while UK professional organizations recommend a more liberal use of parenteral iron. The reason for these disparate recommendations is that few high-quality studies comparing oral to parenteral iron have been conducted in developed countries, and the potential impact of parental iron treatment on obstetric and perinatal outcomes remains unclear. We propose the first randomized-controlled trial in the United States describing the effectiveness and safety of treating pregnant women with iron-deficiency anemia with a protocol including parenteral iron compared with a protocol based on oral iron.

Detailed Description

Iron deficiency is the most common cause of anemia in pregnancy worldwide, and, when severe, can have serious consequences for mothers and babies. In the U.S., anemia affects nearly 20% of pregnancies and the majority is iron-deficiency anemia. Therefore, treatment of iron-deficiency anemia with iron supplementation is recommended.1 However, there is controversy about the treatment strategies.

The American College of Obstetrics and Gynecology recommends oral iron supplementation for iron-deficiency anemia in pregnancy, with parental iron reserved only for the "rare patient who cannot tolerate or will not take oral iron" (1) Conversely, guidelines from the U.K. are more liberal on the use of parental iron for the treatment of iron-deficiency anemia in pregnancy (2). Both treatment guidelines are based on limited data regarding the risks and benefits of parental iron for treatment of iron-deficiency anemia in pregnancy. The majority of randomized trials were conducted in developing country settings. In fact, few high-quality studies have been conducted in developed countries, and none has been conducted in the U.S. Moreover, there is limited data from prior studies on the impact of parental iron treatment on perinatal outcomes. The most recent Cochrane review including mostly from trials conducted in low-income countries found that, although parenteral iron improved hemoglobin levels and iron stores than the oral route, no clinical outcomes were assessed and there were insufficient data on adverse effects (3). The authors concluded that "large, good quality trials, assessing clinical outcomes including adverse effects … are required" (3).

This randomized controlled trial aims to assess the effectiveness and safety of treating pregnant women with iron-deficiency anemia with a protocol including parenteral iron compared with a protocol based on oral iron. We hypothesize that treating iron-deficiency anemia with parental iron is associated with improved maternal and neonatal outcomes compared with a protocol based on oral iron. To increase generalizability of the findings, we will use broad inclusion criteria and analyze data using the intention-to-treat principle.

Study TypeInterventional
Study PhasePhase 4
Estimated Enrollment
120
Allocation
Randomized
Interventional Model
Parallel Assignment
Masking
Double
Primary Purpose
Treatment
Conditions
Iron Deficiency Anemia of Pregnancy
Iron Malabsorption
Target Follow-Up Duration N/A
Biospecimen:
N/A
Sampling MethodN/A
Study PopulationN/A
Intervention
Drug: Iron dextran

Single intravenous infusion of iron dextran 1000mg.

Other Names
Experimental
Drug: Ferrous sulfate 325mg

Oral iron supplementation with ferrous sulfate 325mg one to three times daily

Other Names
Active comparator
Study Groups/Cohorts
Intravenous iron dextran infusion
Women randomized to receive intravenous iron infusion will receive a single infusion of dextran 1000mg IV as an inpatient on the antepartum or Labor & Delivery Unit. They will receive continuous fetal monitoring for 30 minutes before and after the infusion as well for the duration of the infusion

Oral ferrous sulfate supplementation
Women randomized to continue oral iron will continue to take ferrous sulfate 325mg one to three tablets daily, with the final dose at the discretion of the patient's obstetric provider.

Study Arms
Experimental Intravenous iron dextran infusion
Women randomized to receive intravenous iron infusion will receive a single infusion of dextran 1000mg IV as an inpatient on the antepartum or Labor & Delivery Unit. They will receive continuous fetal monitoring for 30 minutes before and after the infusion as well for the duration of the infusion
Drug : Iron dextran
Single intravenous infusion of iron dextran 1000mg.

Active Comparator Oral ferrous sulfate supplementation
Women randomized to continue oral iron will continue to take ferrous sulfate 325mg one to three tablets daily, with the final dose at the discretion of the patient's obstetric provider.
Drug : Ferrous sulfate 325mg
Oral iron supplementation with ferrous sulfate 325mg one to three times daily

Arm Intervention/Treatment
Experimental Intravenous iron dextran infusion
Women randomized to receive intravenous iron infusion will receive a single infusion of dextran 1000mg IV as an inpatient on the antepartum or Labor & Delivery Unit. They will receive continuous fetal monitoring for 30 minutes before and after the infusion as well for the duration of the infusion
Drug : Iron dextran
Active Comparator Oral ferrous sulfate supplementation
Women randomized to continue oral iron will continue to take ferrous sulfate 325mg one to three tablets daily, with the final dose at the discretion of the patient's obstetric provider.
Drug : Ferrous sulfate 325mg

Recruitment Information

Recruitment Status:Not yet recruiting
Enrollment120
Completion DateAugust 01, 2019
Eligibility Criteria: Inclusion Criteria:
- Iron-deficiency anemia (serum ferritin <30 micrograms, normal hemoglobin electrophoresis, and hemoglobin <10 mg/dL), planned delivery at Barnes-Jewish Hospital

Exclusion Criteria:
- Non-iron-deficiency anemia, multiple gestation, prenatally diagnosed major fetal anomalies, known aneuploidy, planned delivery at other hospital, inability to obtain consent
GenderFemale
Age N/A to N/A
Accepts Healthy VolunteersNo
Contacts
Listed Location Countries
United States

Administrative Information

NCT Number:NCT03438227
Other Study ID Numbers
201712110
Has Data Monitoring CommitteeYes
U.S. FDA-regulated Product Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Device Product Not Approved or Cleared by U.S. FDA: No
IPD Sharing Statement
Not Available
Responsible Party,
Study Sponsor
Washington University School of Medicine
Collaborators
Not Available
Investigators
Principal Investigator
Adam K Lewkowitz, MD
Washington University School of Medicine