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

Sponsor

Indiana University (Other)

Overall Status

Completed

CT.gov ID

NCT03438227

Collaborator

(none)

Enrollment

Locations

Arms

20.5

Actual Duration (Months)

Patients Per Site

1.3

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Iron Deficiency Anemia of Pregnancy Iron Malabsorption	Drug: Iron dextran Drug: Ferrous sulfate 325mg	Phase 4

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 Design

Study Type:

Interventional

Actual Enrollment :

52 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

All participants at less than 28 weeks gestation will have an anemia evaluation and work up per standard prenatal care. Those who meet a clinical diagnosis of iron-deficiency anemia will initiate oral iron and have their CBC rechecked between 24 and 28 weeks gestation. If their hemoglobin is less than 10 mg/dL, they will be randomized to either continue their oral iron supplementation or receive a single intravenous dextran iron transfusion. If the patient is enrolled after 28 weeks and receives a diagnosis of iron deficiency anemia, she will be randomized at that time.All participants at less than 28 weeks gestation will have an anemia evaluation and work up per standard prenatal care. Those who meet a clinical diagnosis of iron-deficiency anemia will initiate oral iron and have their CBC rechecked between 24 and 28 weeks gestation. If their hemoglobin is less than 10 mg/dL, they will be randomized to either continue their oral iron supplementation or receive a single intravenous dextran iron transfusion. If the patient is enrolled after 28 weeks and receives a diagnosis of iron deficiency anemia, she will be randomized at that time.

Masking:

Double (Investigator, Outcomes Assessor)

Masking Description:

The research team will be blinded to the patients' treatment arm. A team of resident physicians who are unfamiliar with the study aims will provide standard obstetric care to all participants.

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Apr 15, 2018

Actual Primary Completion Date :

Dec 31, 2019

Actual Study Completion Date :

Dec 31, 2019

Arms and Interventions

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 Single intravenous infusion of iron dextran 1000mg. Other Names: Experimental
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 Other Names: Active comparator

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

Single intravenous infusion of iron dextran 1000mg.

Other Names:

Experimental

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

Other Names:

Active comparator

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

Incidence of Medication Adverse events [Safety and Tolerability] [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 [On day after participant delivered her infant (i.e. postpartum day #1)]
Hemoglobin
Maternal outcome: incidence of blood transfusion [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 [Once, at infant delivery]
Whether infant was delivered vaginally or via cesarean section
Neonatal outcomes: gestational age at delivery [Once, at infant delivery]
Gestational age at delivery
Neonatal outcomes: birth weight [Obtained once, at infant delivery]
Infant birth weight
Neonatal outcomes: umblical cord gases [Drawn once from umbilical cord segment at birth]
Umbilical cord gases
Neonatal outcomes: APGAR scores [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 [Drawn once from umbilical cord segment at birth]
Neonatal hemoglobin
Neonatal outcomes: neonatal morbidity composite [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

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Indiana University School of Medicine	Indianapolis	Indiana	United States	46202
2	Center for Outpatient Health, Washington University in St. Louis	Saint Louis	Missouri	United States	63110