Intravenous Iron Versus Oral Iron for the Treatment of Iron Deficiency Anemia (IDA)

Randomized Control Trial: Intravenous Iron Versus Oral Iron for the Treatment of Iron Deficiency Anemia in Pregnancy

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.

Study Overview

• Status: Recruiting
• Conditions: Iron Deficiency Anemia of Pregnancy
• Intervention / Treatment: Drug: Venofer 200 MG Per 10 ML Injection; Drug: Ferrous sulfate

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.

• Study Type: Interventional
• Enrollment (Estimated): 900
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Colton, California, United States, 92324
      • Recruiting
      • Arrowhead Regional Medical Center
      • Contact: Guillermo Valenzuela, MD; Phone Number: 909-580-4145; Email: jvalenzuelar@me.com
      • Principal Investigator: Tina M Bui, DO
      • Sub-Investigator: Kristina Roloff, DO
      • Sub-Investigator: Guillermo Valenzuela, MD
      • Sub-Investigator: Lily Zhu, DO
      • Sub-Investigator: Phoebe Jen, DO
      • Sub-Investigator: Mary Tsaturian, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 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.	Drug: Venofer 200 MG Per 10 ML Injection; 200 mg IV every 2 days until the targeted dose; Other Names: Iron sucrose
Placebo Comparator: Oral iron; Ferrous sulfate 325 mg orally every other day on an empty stomach with lemon/orange water until delivery.	Drug: Ferrous sulfate; Take 1 tablet every other day with lemon/orange juice

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hemoglobin difference	Change in hemoglobin level after intervention, larger difference mean more improvement in Hgb	Hemoglobin level obtained prior to treatment and then 4 weeks later
Ferritin difference	Change in ferritin level after intervention, larger difference mean more improvement in ferritin level	Ferritin level obtained prior to treatment and then 4 weeks later
Delivery Hemoglobin	Comparing pre-delivery hemoglobin levels	Obtained at time of delivery
Rates of blood transfusion	Comparing rates of blood transfusion at time of delivery between the 2 groups. The number of units transfused will be collected and compared among the groups	At time of delivery until 6 weeks postpartum
Symptoms	Comparing number of anemia symptoms before and after treatment. There are 11 anemia symptoms on the questionnaire. Using a Likert scale from 0 (no symptoms) to 5 (severe symptoms) patient mark each one. The score is totaled up and can range from 0-55.	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Preterm delivery	Comparing hemoglobin levels to gestational age at delivery	At the time of delivery
Depression	Edinburgh postnatal depression scale at first prenatal visit and postpartum. 10 questions with total score between 0-30. Higher score indicated increase risk for depression.	Duration of the pregnancy (up to 40 weeks) and up to 2 months postpartum
Birthweight	Comparing birthweight to hemoglobin levels at time of admission	At time of delivery

Collaborators and Investigators

• Sponsor: Arrowhead Regional Medical Center

Publications and helpful links

General Publications

• Froessler B, Palm P, Weber I, Hodyl NA, Singh R, Murphy EM. The Important Role for Intravenous Iron in Perioperative Patient Blood Management in Major Abdominal Surgery: A Randomized Controlled Trial. Ann Surg. 2016 Jul;264(1):41-6. doi: 10.1097/SLA.0000000000001646.
• Anemia in Pregnancy: ACOG Practice Bulletin, Number 233. Obstet Gynecol. 2021 Aug 1;138(2):e55-e64. doi: 10.1097/AOG.0000000000004477.
• 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.
• Tigga MP, Debbarma AP. A comparative study to evaluate oral iron and intravenous iron sucrose for treatment of anemia in pregnancy in a poor socioeconomic region of Northeast India. Ci Ji Yi Xue Za Zhi. 2019 Jul 24;32(3):258-261. doi: 10.4103/tcmj.tcmj_99_19. eCollection 2020 Jul-Sep.
• Chua S, Gupta S, Curnow J, Gidaszewski B, Khajehei M, Diplock H. Intravenous iron vs blood for acute post-partum anaemia (IIBAPPA): a prospective randomised trial. BMC Pregnancy Childbirth. 2017 Dec 19;17(1):424. doi: 10.1186/s12884-017-1596-x.
• Ng O, Keeler BD, Mishra A, Simpson JA, Neal K, Al-Hassi HO, Brookes MJ, Acheson AG. Iron therapy for preoperative anaemia. Cochrane Database Syst Rev. 2019 Dec 7;12(12):CD011588. doi: 10.1002/14651858.CD011588.pub3.
• Nicholls G, Mehta R, McVeagh K, Egan M. The Effects of Intravenous Iron Infusion on Preoperative Hemoglobin Concentration in Iron Deficiency Anemia: Retrospective Observational Study. Interact J Med Res. 2022 Feb 3;11(1):e31082. doi: 10.2196/31082.
• 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.
• 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.
• 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.
• Govindappagari S, Burwick RM. Treatment of Iron Deficiency Anemia in Pregnancy with Intravenous versus Oral Iron: Systematic Review and Meta-Analysis. Am J Perinatol. 2019 Mar;36(4):366-376. doi: 10.1055/s-0038-1668555. Epub 2018 Aug 19.
• Stoffel NU, Zeder C, Brittenham GM, Moretti D, Zimmermann MB. Iron absorption from supplements is greater with alternate day than with consecutive day dosing in iron-deficient anemic women. Haematologica. 2020 May;105(5):1232-1239. doi: 10.3324/haematol.2019.220830. Epub 2019 Aug 14.

Study record dates

Study Major Dates

• Study Start (Actual): November 21, 2023
• Primary Completion (Estimated): December 30, 2025
• Study Completion (Estimated): December 30, 2025

Study Registration Dates

• First Submitted: April 8, 2024
• First Submitted That Met QC Criteria: April 10, 2024
• First Posted (Actual): April 16, 2024

Study Record Updates

• Last Update Posted (Actual): April 16, 2024
• Last Update Submitted That Met QC Criteria: April 10, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Pregnancy; Anemia; Iron deficiency; Intravenous iron
• Additional Relevant MeSH Terms: Metabolic Diseases; Hematologic Diseases; Nutrition Disorders; Anemia, Hypochromic; Iron Metabolism Disorders; Malnutrition; Anemia, Iron-Deficiency; Anemia; Deficiency Diseases; Iron Deficiencies; Hematinics; Ferric Oxide, Saccharated
• Other Study ID Numbers: 23-55

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes