Clinical trial NCT06366698: Intravenous Iron Versus Oral Iron for the Treatment of Iron Deficiency Anemia
Official title: Randomized Control Trial: Intravenous Iron Versus Oral Iron for the Treatment of Iron Deficiency Anemia in Pregnancy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Iron Deficiency Anemia of Pregnancy
Keywords: Anemia
Iron deficiency
Pregnancy
Intravenous iron
Lead sponsor: Arrowhead Regional Medical Center
Sponsor class: OTHER
First posted: 2024-04-16
Enrollment: 900
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Patients are initially randomized to either PO or IV iron, after the initial 4-week treatment patients in the PO iron group can switch to IV iron if labs continue to show persist iron deficiency anemia.
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Hemoglobin difference
timeFrame: Hemoglobin level obtained prior to treatment and then 4 weeks later
measure: Ferritin difference
timeFrame: Ferritin level obtained prior to treatment and then 4 weeks later
measure: Delivery Hemoglobin
timeFrame: Obtained at time of delivery
measure: Rates of blood transfusion
timeFrame: At time of delivery until 6 weeks postpartum
measure: Symptoms
timeFrame: 4 weeks
Secondary outcomes:
measure: Preterm delivery
timeFrame: At the time of delivery
measure: Depression
timeFrame: Duration of the pregnancy (up to 40 weeks) and up to 2 months postpartum
measure: Birthweight
timeFrame: At time of delivery
Other outcomes:
Locations:
city: Colton
country: United States
facility: Arrowhead Regional Medical Center
state: California
Study officials:
References:
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