Intravenous Iron Versus Oral Iron for the Treatment of Iron Deficiency Anemia

NCT ID: NCT06366698

Last Updated: 2024-04-16

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 900 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-11-21
• Study Completion Date: 2025-12-30

Brief Summary

This study aims to assess whether administering intravenous iron early in pregnancy, compared to standard oral iron treatment, can enhance hemoglobin levels before delivery and reduce the need for blood transfusions in patients with iron deficiency anemia. Patients diagnosed with iron deficiency anemia were randomly assigned to receive either oral or intravenous iron. Before treatment initiation, patients completed a symptom questionnaire baseline hemoglobin, and ferritin levels were measured. Follow-up visits occurred four weeks later and at 24 to 28 weeks gestation, involving reassessment of symptoms, laboratory testing, and monitoring of treatment adherence. Final hemoglobin levels were determined before delivery, and data on the need for blood transfusion at delivery were recorded.

Detailed Description

Iron deficiency anemia is a prevalent health concern affecting approximately a quarter of the global population. In specific high-risk subgroups such as pregnancy, the occurrence of anemia is even higher. This condition is associated with adverse outcomes such as increased risks of blood transfusion, longer hospital stays, slower recovery, and depression, along with pregnancy risks such as preterm birth and low birth weight. Furthermore, infants born to iron-deficient mothers are at risk for delayed childhood growth and cognitive development. Preoperative optimization is crucial for improving clinical outcomes, as iron deficiency anemia accounts for over 80% of anemia cases in these patients.

Traditionally, oral (PO) iron supplementation has been the standard approach recommended by the American College of Obstetrics and Gynecology (ACOG) for preventing and addressing iron deficiency due to its simplicity and cost-effectiveness. However, it is marred by poor adherence to therapy and a high incidence of gastrointestinal side effects. While numerous publications have documented the safety and efficacy of intravenous (IV) iron, its utilization remains limited. Currently, IV iron is primarily reserved for patients who exhibit intolerance or an inadequate response to oral therapy. At our institution, we have taken proactive steps by administering IV iron infusions to many of our patients at an earlier gestational age, given the high rate of non-compliance with oral iron therapy. Our hypothesis proposes that individuals with iron deficiency anemia, defined as a serum ferritin level of less than 30 ng/mL (with 92% sensitivity and 98% specificity compared to hemoglobin (Hgb) levels), who receive IV iron infusions, will achieve higher Hgb levels upon admission and experience reduced rates of blood transfusions.

This study aims to assess the impact of IV iron infusions on pregnant patients with iron deficiency anemia. We hope that implementing this study will help improve overall population health. We hypothesize that individuals with iron deficiency anemia who receive IV iron infusions will attain higher Hgb levels at the time of admission and experience reduced rates of blood transfusions at the time of delivery.

After obtaining the patient's consent, they will be randomized into either of the two treatment options. All odd numbers will be in the oral iron group and even numbers enrolled into the IV iron group. We intend to administer Ferrous sulfate 325 mg orally every other day on an empty stomach with lemon/orange water, as numerous randomized control trials have demonstrated that increasing the iron dose does not lead to improved efficacy. Venofer 200 mg will be given every other day until the patient reaches their calculated iron deficit. The dose of IV iron will be calculated according to the Ganzoni formula: total iron dose (mg) = body weight (kg) x (target Hgb - baseline Hgb (g/dL)) × 0.24 + 500 mg. Our target Hgb will be 11.0 g/dL.

Patients will be given a symptom questionnaire at the time of enrollment to fill out. We will analyze the patient's ferritin, iron, total iron binding capacity (TIBC), Hgb level, mean corpuscular volume (MCV), and Hgb electrophoresis, which are routinely obtained on the first visit with prenatal labs. Four weeks after initiating treatment, patients will fill out a symptom and side effect questionnaire, and if on PO iron, their compliance will be assessed. Complete blood count (CBC) and iron studies will be repeated at that time. Other patient information such as admission CBC, post-delivery CBC, height, weight, body mass index (BMI), age, parity, gestational age at delivery, quantitative blood loss, route of delivery, need for blood transfusion, number of IV iron infusions, fetal birth weight, and antepartum/intrapartum/postpartum complications such as diabetes, preeclampsia/eclampsia, chorioamnionitis, and hemorrhage, etc., neonatal intensive care unit (NICU) admission as well as Edinburgh depression screening results, will be obtained from medical records. This information will be used for secondary outcomes analysis and to ensure there are no confounding factors. Statistical comparisons between groups will be performed using the two-way T-test followed by Tukey's test, or post hoc Student-Newman-Keuls tests. A P < .05 will be considered a statistically significant difference among groups.

Conditions

Iron Deficiency Anemia of Pregnancy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Intravenous iron

Venofer 200 mg will be given every other day until the patient reaches their calculated in deficit dose. The does of IV iron will be calculated according to the Ganzoni formula: total iron dose (mg) = body weight (kg) x (target Hgb - baseline Hgb (g/dL)) × 0.24 + 500 mg.14 Our target Hgb will be 11.0 g/dL. The determination of the treatment duration and dosage will be based on the calculation of the iron deficit.

Group Type: ACTIVE_COMPARATOR

Venofer 200 MG Per 10 ML Injection

Intervention Type: DRUG

200 mg IV every 2 days until the targeted dose

Oral iron

Ferrous sulfate 325 mg orally every other day on an empty stomach with lemon/orange water until delivery.

Group Type: PLACEBO_COMPARATOR

Ferrous sulfate

Intervention Type: DRUG

Take 1 tablet every other day with lemon/orange juice

Interventions

Venofer 200 MG Per 10 ML Injection

200 mg IV every 2 days until the targeted dose

Intervention Type: DRUG

Ferrous sulfate

Take 1 tablet every other day with lemon/orange juice

Intervention Type: DRUG

Other Intervention Names

Iron sucrose

Eligibility Criteria

Inclusion Criteria

• Age > 18 years of age
• Ferritin level < 30 ng/mL
• Singe gestation
• Gestational age up to 36 weeks as iron therapy after this has shown to be not beneficial at time of delivery. We will still plan to treat patients > 36 weeks but not include them in the final analysis
• Plan to delivery at Arrowhead Regional Medical Center (ARMC)

Exclusion Criteria

• Maternal age < 18 years of age
• Incarcerated patients
• Multifetal gestation
• Acute liver/kidney disease
• Active infections
• Known hematological malignancy
• Other causes of anemia such as alpha/beta thalassemia, sickle cell disease, Folate/B12 deficiency, and anemia of chronic diseases
• Known hypersensitivity with IV iron
• Severe symptoms of anemia requiring blood transfusion

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Arrowhead Regional Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Arrowhead Regional Medical Center

Colton, California, United States

Site Status: RECRUITING

Countries

United States

Facility Contacts

Guillermo Valenzuela, MD

Role: primary

jvalenzuelar@me.com

909-580-4145

References

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Reference Type: BACKGROUND

PMID: 26817624 (View on PubMed)

Anemia in Pregnancy: ACOG Practice Bulletin, Number 233. Obstet Gynecol. 2021 Aug 1;138(2):e55-e64. doi: 10.1097/AOG.0000000000004477.

Reference Type: BACKGROUND

PMID: 34293770 (View on PubMed)

Achebe MM, Gafter-Gvili A. How I treat anemia in pregnancy: iron, cobalamin, and folate. Blood. 2017 Feb 23;129(8):940-949. doi: 10.1182/blood-2016-08-672246. Epub 2016 Dec 29.

Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

PMID: 29258541 (View on PubMed)

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Reference Type: RESULT

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Reference Type: RESULT

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Lewkowitz 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.

Reference Type: RESULT

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Wong L, Smith S, Gilstrop M, Derman R, Auerbach S, London N, Lenowitz S, Bahrain H, McClintock J, Auerbach M. Safety and efficacy of rapid (1,000 mg in 1 hr) intravenous iron dextran for treatment of maternal iron deficient anemia of pregnancy. Am J Hematol. 2016 Jun;91(6):590-3. doi: 10.1002/ajh.24361. Epub 2016 Apr 13.

Reference Type: RESULT

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Hansen R, Sommer VM, Pinborg A, Krebs L, Thomsen LL, Moos T, Holm C. Intravenous ferric derisomaltose versus oral iron for persistent iron deficient pregnant women: a randomised controlled trial. Arch Gynecol Obstet. 2023 Oct;308(4):1165-1173. doi: 10.1007/s00404-022-06768-x. Epub 2022 Sep 15.

Reference Type: RESULT

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Reference Type: RESULT

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Reference Type: RESULT

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Provided Documents

Document Type: Informed Consent Form

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Other Identifiers

23-55

Identifier Type: -

Identifier Source: org_study_id