Iron Deficiency Anemia of PregnancyPhase 4IVIDANCT03438227
Intravenous Iron for Iron-deficiency Anemia in Pregnancy: a Randomized Controlled Trial
A Phase 4 study testing Iron dextran and Ferrous sulfate 325mg in people with Iron Deficiency Anemia of Pregnancy and Iron Malabsorption, run by Indiana University at 2 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Any age, women only
- Conditions the study is for
- Iron Deficiency Anemia of Pregnancy, Iron Malabsorption
- What is being tested?
- Iron dextran and Ferrous sulfate 325mg
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 38 participants
- Where
- 2 sitesUnited States
- Study dates
- 15 Apr 2018to 31 Dec 2019
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- Women only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Iron-deficiency anemia (serum ferritin <30 micrograms, normal hemoglobin electrophoresis, and hemoglobin <10 mg/dL), planned delivery at Barnes-Jewish Hospital
Who cannot join
- Non-iron-deficiency anemia, multiple gestation, prenatally diagnosed major fetal anomalies, known aneuploidy, planned delivery at other hospital, inability to obtain consent
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Indiana University School of Medicine
Indianapolis, Indiana, 46202
Center for Outpatient Health, Washington University in St. Louis
St Louis, Missouri, 63110
About this study
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 United Kingdom 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.
Read the 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 United States, 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 United Kingdom. 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 United States 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.
- Being tested
- Iron dextran, Ferrous sulfate 325mg
- Keywords
- Iron Deficiency Anemia of Pregnancy, oral iron supplementation, parenteral iron supplementation, maternal anemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Iron dextranDrug
Also called Experimental
Single intravenous infusion of iron dextran 1000mg.
Ferrous sulfate 325mgDrug
Also called Active comparator
Oral iron supplementation with ferrous sulfate 325mg one to three times daily
| Study group | Role | What they receive |
|---|---|---|
| Intravenous iron dextran infusion | Experimental | 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 Receives: Drug: Iron dextran |
| Oral ferrous sulfate supplementation | Active comparator | 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. Receives: Drug: Ferrous sulfate 325mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maternal Anemia at Delivery
Number of participants with maternal hemoglobin <11g/dl at delivery
Measured: At delivery
Secondary outcomes (13)
Maternal Hemoglobin at Delivery
Maternal hemoglobin on admission to inpatient obstetrics unit for delivery
Measured: On admission to inpatient obstetrics unit for delivery
Number of Participants With Medication Adverse Events
Participants reporting symptoms when contacted by via telephone 2 - 3 days after their infusion of intravenous iron or initiation of oral iron
Measured: 2 - 3 days after single intravenous iron infusion or initiation of oral iron
Maternal Hemoglobin Below 10g/dl at Delivery
Number of participants with hemoglobin below 10g/dl at delivery
Measured: At delivery
Maternal Ferritin at Delivery
Maternal serum ferritin level in μg/L at delivery
Measured: At delivery
Number of Participants Who Received Blood Transfusion
Participant receiving transfusion of packed red blood cells during admission for delivery of infant obtained via medical chart review.
Measured: During inpatient admission for delivery of neonate
Mode of Delivery
Whether infant was delivered vaginally or via cesarean section
Measured: Once, at infant delivery
Gestational Age at Delivery
Gestational age in weeks at delivery
Measured: Once, at infant delivery
Birth Weight
Neonatal weight at delivery
Measured: Obtained once, at infant delivery
Umbilical Cord Arterial pH
Umbilical cord arterial pH obtained at delivery
Measured: Drawn once from umbilical cord segment at delivery
APGAR Scores at 1 Minutes of Life
The APGAR score, named after the Virginia Apgar, pediatrician who came up with it, measures the physical condition of a newborn infant on a scale ranging from a minimum of 0 (worsts) to a maximum of 10 (best).
Measured: Obtained at 1 minute of life
Neonatal Hemoglobin
Neonatal hemoglobin in g/dl at delivery
Measured: Drawn once from umbilical cord segment at birth
Composite Neonatal Morbidity (Defined by the Occurrence of One or More of 10 Neonatal Morbidities.
Neonatal morbidity composite, defined by the occurrence of one or more of the following neonatal morbidities: neonatal seizures (diagnosed by clinician), intraventricular hemorrhage (diagnosed by clinician on brain MRI or Ultrasound), hypoxic-ischemic encephalopathy (diagnosed by clinician), neonatal hypothermic therapy (brain cooling as documented on inpatient record, sepsis (diagnosed by blood culture), respiratory distress syndrome (diagnosed by clinician), hyperbilirubinemia requiring photo therapy (diagnosed by clinician), birth injury (diagnosed by clinician), or meconium aspiration syndrome (diagnosed by clinician), neonatal intensive care unit admission (documented in the inpatient record).
Measured: At birth
Neonatal Ferritin
Neonatal ferritin in ug/L at delivery
Measured: Drawn once from umbilical cord segment at birth
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Feb 2018
- Study start15 Apr 2018
- Primary completion31 Dec 2019
- Study completion31 Dec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Iron Deficiency Anemia of PregnancyStudies of the same condition, open and under way.
- More trials run by Indiana UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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 Complete Blood Count 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 blind
- Who is masked
- Investigator, Outcomes assessor
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- Indiana University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Method Tuuli, Indiana University
- Investigators
- Method Tuuli, MD, Principal investigator, Indiana University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03438227
- Sponsor's protocol ID
- 1809251633
- Acronym
- IVIDA
- Status last verified
- May 2024
- First submitted
- 25 Jan 2018
- Last updated
- 11 Jun 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 95: anemia in pregnancy. Obstet Gynecol. 2008 Jul;112(1):201-7. doi: 10.1097/AOG.0b013e3181809c0d.
PubMed 18591330Pavord S, Myers B, Robinson S, Allard S, Strong J, Oppenheimer C; British Committee for Standards in Haematology. UK guidelines on the management of iron deficiency in pregnancy. Br J Haematol. 2012 Mar;156(5):588-600. doi: 10.1111/j.1365-2141.2011.09012.x.
PubMed 22512001Reveiz L, Gyte GM, Cuervo LG, Casasbuenas A. Treatments for iron-deficiency anaemia in pregnancy. Cochrane Database Syst Rev. 2011 Oct 5;2011(10):CD003094. doi: 10.1002/14651858.CD003094.pub3.
PubMed 21975735Lewkowitz AK, Stout MJ, Cooke E, Deoni SC, D'Sa V, Rouse DJ, Carter EB, Tuuli MG. Intravenous versus Oral Iron for Iron-Deficiency Anemia in Pregnancy (IVIDA): A Randomized Controlled Trial. Am J Perinatol. 2022 Jun;39(8):808-815. doi: 10.1055/s-0041-1740003. Epub 2021 Nov 28.
PubMed 34839481
Study at a glance
From the registry record, last updated by the sponsor on 11 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Intravenous Iron for Iron-deficiency Anemia in Pregnancy: a Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT03438227
- Acronym / sponsor ID
- IVIDA / 1809251633
- Keywords
- Iron Deficiency Anemia of Pregnancy, oral iron supplementation, parenteral iron supplementation, maternal anemia
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 38 participants (actual)
- Lead sponsor
- Indiana UniversityUniversity, hospital or other
- Study start
- 15 Apr 2018 (actual)
- Primary completion
- 31 Dec 2019 (actual)
- Study completion
- 31 Dec 2019 (actual)
- First posted
- 19 Feb 2018 (actual)
- Results
- Posted 11 Jun 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 United Kingdom 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 United States, 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 United Kingdom. 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 United States 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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (investigator, outcomes assessor)
- Number of arms
- 2
- 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 Complete Blood Count 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.
| Arm | Type | Receives |
|---|---|---|
| Intravenous iron dextran infusion | Experimental | Drug: Iron dextranWomen 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 | Active comparator | Drug: Ferrous sulfate 325mgWomen 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. |
Who may qualify
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (1 listed)
- Iron-deficiency anemia (serum ferritin <30 micrograms, normal hemoglobin electrophoresis, and hemoglobin <10 mg/dL), planned delivery at Barnes-Jewish Hospital
Key exclusion criteria (1 listed)
- Non-iron-deficiency anemia, multiple gestation, prenatally diagnosed major fetal anomalies, known aneuploidy, planned delivery at other hospital, inability to obtain consent
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Iron dextranAlso: ExperimentalSingle intravenous infusion of iron dextran 1000mg. | Drug | Intravenous iron dextran infusion |
| Ferrous sulfate 325mgAlso: Active comparatorOral iron supplementation with ferrous sulfate 325mg one to three times daily | Drug | Oral ferrous sulfate supplementation |
Primary outcome
Maternal Anemia at Delivery
Time frame: At delivery
Number of participants with maternal hemoglobin <11g/dl at delivery
13 secondary outcomes
Maternal Hemoglobin at Delivery
Time frame: On admission to inpatient obstetrics unit for delivery
Number of Participants With Medication Adverse Events
Time frame: 2 - 3 days after single intravenous iron infusion or initiation of oral iron
Maternal Hemoglobin Below 10g/dl at Delivery
Time frame: At delivery
Maternal Ferritin at Delivery
Time frame: At delivery
Number of Participants Who Received Blood Transfusion
Time frame: During inpatient admission for delivery of neonate
Mode of Delivery
Time frame: Once, at infant delivery
Gestational Age at Delivery
Time frame: Once, at infant delivery
Birth Weight
Time frame: Obtained once, at infant delivery
Umbilical Cord Arterial pH
Time frame: Drawn once from umbilical cord segment at delivery
APGAR Scores at 1 Minutes of Life
Time frame: Obtained at 1 minute of life
Neonatal Hemoglobin
Time frame: Drawn once from umbilical cord segment at birth
Composite Neonatal Morbidity (Defined by the Occurrence of One or More of 10 Neonatal Morbidities.
Time frame: At birth
Neonatal Ferritin
Time frame: Drawn once from umbilical cord segment at birth
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jun 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 18591330American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 95: anemia in pregnancy. Obstet Gynecol. 2008 Jul;112(1):201-7. doi: 10.1097/AOG.0b013e3181809c0d.
- Background: PubMed 22512001Pavord S, Myers B, Robinson S, Allard S, Strong J, Oppenheimer C; British Committee for Standards in Haematology. UK guidelines on the management of iron deficiency in pregnancy. Br J Haematol. 2012 Mar;156(5):588-600. doi: 10.1111/j.1365-2141.2011.09012.x.
- Background: PubMed 21975735Reveiz L, Gyte GM, Cuervo LG, Casasbuenas A. Treatments for iron-deficiency anaemia in pregnancy. Cochrane Database Syst Rev. 2011 Oct 5;2011(10):CD003094. doi: 10.1002/14651858.CD003094.pub3.
- Derived from this study: PubMed 34839481Lewkowitz AK, Stout MJ, Cooke E, Deoni SC, D'Sa V, Rouse DJ, Carter EB, Tuuli MG. Intravenous versus Oral Iron for Iron-Deficiency Anemia in Pregnancy (IVIDA): A Randomized Controlled Trial. Am J Perinatol. 2022 Jun;39(8):808-815. doi: 10.1055/s-0041-1740003. Epub 2021 Nov 28.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Method Tuuli, MD principal investigator
Indiana University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Iron dextran and Ferrous sulfate 325mg in people with Iron Deficiency Anemia of Pregnancy and Iron Malabsorption, run by Indiana University at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Jun 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maternal Anemia at Delivery (time frame: At delivery). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03438227, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jun 2024.