IV Iron Sucrose vs Oral FeSO4 in Treating IDA in Pediatric IBD

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety and efficacy of intravenous iron sucrose in comparison to oral ferrous sulfate in improving iron deficiency anemia in children with inflammatory bowel disease.

Detailed Description
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Iron deficiency anemia (IDA) is very common among children with inflammatory bowel disease. Causes in this population are multi-factorial, including decreased absorption due to intestinal disease, increased losses due to bleeding from the gastrointestinal (GI) tract, and poor nutrition. IDA can cause significant impaired physical activity and is associated with developmental and cognitive abnormalities in children and adolescents. Oral ferrous sulfate has been traditionally used to treat iron deficiency anemia, but this is associated with limitations. Studies have shown that only a part of the oral iron is absorbed and the non-absorbed iron salts can be toxic to the intestinal mucosa, and was also theorized to be capable of activating the Inflammatory Bowel Disease (IBD). Use of intravenous iron sucrose has been used in other populations with iron deficiency anemia such as those with chronic kidney disease and children with significant blood loss after spinal surgery. The aim of this study is to determine the safety and efficacy of intravenous iron sucrose in improving iron deficiency anemia in children with inflammatory bowel disease (in comparison to oral ferrous sulfate).

Official Title
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Intravenous Iron Sucrose Versus Oral Ferrous Sulfate in Treating Iron Deficiency Anemia in Pediatric Inflammatory Bowel Disease

Conditions
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Iron Deficiency Anemia, Inflammatory Bowel Disease

Intervention / Treatment
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* Drug: Intravenous iron sucrose
* Drug: Oral ferrous sulfate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: IBD Diagnosis. IDA (defined as a hemoglobin (Hb) concentration of ≤10.5 g/dL females) or Hb ≤11.0 g/dL (males) and Mean Corpuscular volume (MCV) < 77 [22] plus transferrin saturation (TSAT) < 20% and/or serum ferritin concentration less than 25 µg/L) 12- 17 years old males or females. A signed parental permission and assent. Assent is not required in those below 13 years of age. We will be including those who have received iron therapy in the past even if they have developed adverse reactions, as long as they have not been anaphylactic. Participants should have been iron free (no iron therapy - oral or IV) for two weeks prior to start of study. Exclusion Criteria: Anemia other than IDA e.g hemolytic anemia, anemia due to Vitamin B12/Folic acid deficiency. Blood transfusion or iron supplementation 2 two weeks or less before starting the study. Iron overload. Renal disease - on medications such as diuretics or blood pressure lowering medications. On renal replacement therapy. Severe reactive airway disease - classified as severe/high-risk asthma Significant cardiac disease - on cardiac medications, including symptomatic congenital cardiac anomalies or with arrhythmias. Anaphylaxis/hypersensitivity reaction to ferrous sulfate and/or iron sucrose Pregnant and nursing women. A serum pregnancy test will be performed at the start of the study and on days 1, 14, and 28. Patients aged 12 years of age and are found to be pregnant are considered victims of child abuse and will be reported to child protective services and the appropriate authorities. Any other severe concurrent illness.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intravenous iron sucrose arm<br> | Drug: Intravenous iron sucrose<br>* Intravenous iron sucrose will be administered on days 1, 7, 14, and 21 using the formula: Total dose: (normal Hb for age - initial Hb)/100 x blood volume (ml) x 3.4 x 1.5. First dose will be infused over 30 minutes, with subsequent doses administered over 15 minutes if no reactions encountered.<br>* Other names: Venofer Luitpold Pharmaceuticals, NDC # 00517-2340-10;|
| Active Comparator: Oral ferrous sulfate<br> | Drug: Oral ferrous sulfate<br>* Oral ferrous sulfate will be administered at 3 mg/kg/day divided into 2 doses for 28 days. A tablet form of ferrous sulfate (325 mg with 65 mg of elemental iron per tablet) will be used.<br>* Other names: Upsher-Smith ferrous sulfate 325 mg tablets NDC# 00245-0108-11;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of IV Iron Sucrose | Safety of IV Iron sucrose is evaluated through timely reporting and thorough description of adverse events. Adverse events related to oral ferrous sulfate will also be reported. Study begins on day of randomization. Iron sucrose is administered on days 1, 7, 14, 21. Follow-up visit is done on day 28 and a follow-up visit or phone call is done on day 49. Oral iron will be taken for 28 days. Patients will be seen in clinic on days 1, 7, 14, 21. With same follow-up as IV iron sucrose. | Up to 56 days | 
| Efficacy of IV Iron sucrose as measured by change in Hb measurement | Efficacy of IV iron sucrose is evaluated through Hb measurement (gm/dl) at baseline and 4 weeks after treatment with intravenous iron sucrose. (increase of 1 gm/dl in 4 weeks is considered significant). This is compared to Hb increase in participants taking oral ferrous sulfate. Study begins on day of randomization. Iron sucrose is administered on days 1, 7, 14, 21. Follow-up visit is done on day 28 and a follow-up visit or phone call is done on day 49. Oral iron will be taken for 28 days. Patients will be seen in clinic on days 1, 7, 14, 21. With same follow-up as IV iron sucrose. | baseline and up to 4 weeks. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| determine effect on iron parameters: change in transferrin saturation | would like to determine change in iron parameters: change in transferrin saturation, ferritin levels, serum iron binding capacity. Study begins on day of randomization. Participants have been identified approximately a week before. Iron sucrose is administered on days 1, 7, 14, 21. Follow-up visit is done on day 28 and a follow-up visit or phone call is done on day 49. Oral iron will be taken for 28 days. Patients will be seen in clinic on days 1, 7, 14, 21. With same follow-up as IV iron sucrose. | baseline, and up to 56 days | 
| clinical disease activity | to evaluate effects of oral FeSO4 and IV iron sucrose on clinical disease activity. Crohns disease activity will be measured by the Pediatric Crohns Disease Activity Index. Ulcerative colitis disease activity will be measured by Truelove and Witt's classification of severity of ulcerative colitis. Both will be measured at baseline and at 4 weeks. Iron sucrose is administered on days 1, 7, 14, 21. F/u visit is done on day 28 and a f/u visit or phone call is done on day 49. Oral iron will be taken for 28 days. Pts will be seen in clinic on days 1, 7, 14, 21.Same f/u as iron sucrose. | baseline up to 56 days | 
| determine effect on iron parameters: change in ferritin levels | would like to determine change in iron parameters: change in transferrin saturation, ferritin levels, serum iron binding capacity. Study begins on day of randomization. Participants have been identified approximately a week before. Iron sucrose is administered on days 1, 7, 14, 21. Follow-up visit is done on day 28 and a follow-up visit or phone call is done on day 49. Oral iron will be taken for 28 days. Patients will be seen in clinic on days 1, 7, 14, 21. With same follow-up as IV iron sucrose. | baseline up to 56 days | 
| determine effect on iron parameters: change in serum iron binding capacity | would like to determine change in iron parameters: change in transferrin saturation, ferritin levels, serum iron binding capacity. Study begins on day of randomization. Participants have been identified approximately a week before. Iron sucrose is administered on days 1, 7, 14, 21. Follow-up visit is done on day 28 and a follow-up visit or phone call is done on day 49. Oral iron will be taken for 28 days. Patients will be seen in clinic on days 1, 7, 14, 21. With same follow-up as IV iron sucrose. | baseline up to 56 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Iron Deficiency Anemia, Inflammatory Bowel Disease, Children