Trial of IV vs Oral Iron Treatment of Iron Deficiency Anemia in the Post-Operative Bariatric Surgical Patient

A Randomized, Placebo-controlled Comparator Trial of IV vs Oral Iron Treatment of Iron Deficiency Anemia in the Post-Operative Bariatric Surgical Patient

Given the limited long-term effectiveness of traditional weight loss methods, bariatric surgery is increasingly becoming the preferred option for sustained weight loss. With the ascendancy of the laparoscopic approach, the two most common procedures are the Roux-en-Y gastric bypass (RYGB) and the vertical sleeve gastrectomy (VSG).

Because bariatric surgery decreases nutrient intake through restriction, malabsorption, or both, and given that obese patients are often malnourished even before surgery, postoperative micronutrient deficiency, particularly of iron, can be a serious complication and difficult to treat. Iron deficiency anemia has been reported to be as high as 49% in the post-bariatric surgical patient.

The current standard for correcting iron deficiency anemia in the post-operative bariatric surgical patient is oral iron supplements. However, oral iron therapy is known for its caustic effects on the gastric mucosa causing gastric irritation, nausea, epigastric discomfort and constipation. These debilitating symptoms lead to poor adherence and lower long and short-term efficacy. Furthermore, iron absorption from oral iron supplements when taken with food in patients with low iron stores ranges from 2 to 13% and without food 5 to 28%. An alternative and more effective method of iron replenishment is the use of intravenous iron. A litany of published trials, without contradiction, show marked superiority of intravenous iron in improving hemoglobin concentrations and iron parameters when compared to historical controls. Nonetheless, the current recommendations of the American Society of Metabolic and Bariatric Surgery nutritional guidelines, state that oral iron supplementation for IDA is the recommended first line of treatment. Studies are lacking that compare the efficacy of oral versus intravenous (IV) iron therapy for the treatment of IDA in the post-bariatric surgical patient.

The aim of our study is to compare two accepted treatments for iron deficiency anemia (oral ferrous sulfate and intravenous ferumoxytol) for efficacy and speed of response in the treatment of IDA in the post-operative bariatric surgical patient. In this study, 104 bariatric surgical post-operative patients will be randomly assigned 52 each to oral or 52 to a single dose IV iron treatment using double-blind procedures.

The primary outcome will be determined at 6 weeks of treatment with a follow-up at 12 months after treatment. Non-responders at 6 weeks after treatment may, if they qualify (based on inclusion/exclusion criteria), have an open-label IV iron treatment and will be followed with the same evaluations used after the first IV iron treatments.

Study Overview

• Status: Recruiting
• Conditions: Iron Deficiency Anemia
• Intervention / Treatment: Drug: Ferumoxytol; Drug: Saline; Drug: Ferrous sulfate tablets; Drug: Vitamin C

• Study Type: Interventional
• Enrollment (Estimated): 104
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Michael Auerbach, MD; Phone Number: 4107804050; Email: mauerbachmd@abhemonc.com
• Study Contact Backup: Name: Stella Rineer, RN; Phone Number: 410 7804050; Email: srineer@yahoo.com

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21237
      • Recruiting
      • Auerbach Hematology and Oncology
      • Contact: Michael Auerbach, MD; Phone Number: 410-780-4050; Email: mauerbachmd@abhemonc.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

1. Aged ≥ 18 years
2. Patients who have undergone a Roux-en Y Gastric Bypass or Vertical Sleeve Gastrectomy and are at least 3 months or more out from surgery.
3. Iron deficiency anemia defined as iron deficient with either ferritin<30 mcg/l, TSAT<20%, or anemia with Hgb<13 g/dL for both males and females.
4. Willingness to participate and signing the informed consent form.

Exclusion criteria:

1. Iron overload or disturbances in utilization of iron (e.g. hemochromatosis and hemosiderosis)
2. Decompensated liver cirrhosis or active hepatitis (ALAT > 3 times upper limit of normal)
3. Serum ferritin > 400 ng/mL or transferrin saturation >40 %
4. Active acute or chronic infections (assessed by clinical judgment that may be indicated by White Blood Cells (WBC) and C-Reactive Protein (CRP) when these are available)
5. Rheumatoid arthritis with symptoms or signs of active inflammation
6. Pregnant and nursing women
7. History of multiple allergies (two or more)
8. Known hypersensitivity to ferumoxytol or oral iron or any excipients in the drug products
9. Previous IV iron treatment for IDA
10. Other iron treatment or blood transfusion within 4 weeks prior to the screening or treatment visit
11. Planned elective surgery during the study
12. Any other medical condition that, in the opinion of Investigator, may cause the subject to be unsuitable for the completion of the study or place the subject at potential risk from being in the study, e.g. a malignancy, uncontrolled hypertension, unstable ischemic heart disease, or uncontrolled diabetes mellitus

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Oral Iron; The subject will receive one IV infusion of ferumoxytol administered as 1020 mg over 30 minutes or an equivalent volume of normal saline. At the time of the infusion, the patient will also be given an opaque bottle, containing either vitamin C tablets or ferrous sulfate 325 mg.	Drug: Ferumoxytol; Ferumoxytol (30 mg/mL) intravenous injection in single use vials.; Drug: Saline; Placebo for Ferumoxytol; Drug: Ferrous sulfate tablets; ferrous sulfate tablets containing 60 mg elemental iron; Drug: Vitamin C; Placebo: Vitamin C, 250 mg, given in the same bottle as the oral iron
Active Comparator: IV Iron; The subject will receive one IV infusion of ferumoxytol administered as 1020 mg over 30 minutes or an equivalent volume of normal saline. At the time of the infusion, the patient will also be given an opaque bottle, containing either vitamin C tablets or ferrous sulfate 325 mg.	Drug: Ferumoxytol; Ferumoxytol (30 mg/mL) intravenous injection in single use vials.; Drug: Saline; Placebo for Ferumoxytol; Drug: Ferrous sulfate tablets; ferrous sulfate tablets containing 60 mg elemental iron; Drug: Vitamin C; Placebo: Vitamin C, 250 mg, given in the same bottle as the oral iron

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Clinical Global Impression - improvement scale (CGI-2) score at 6 weeks after treatment begins.	The CGI-2 is a measure of treatment response and the efficacy of the treatment based on a 1 to 7 scale where 1 is "very much better" and 7 "very much worse"	6 weeks
Change in hemoglobin concentration		6 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in ferritin > 20%	6 weeks
Change in Transferrin saturation (TSAT) >19%	6 weeks
Quality of Life by visual linear analog scale (LASA)	6 weeks

Collaborators and Investigators

• Sponsor: Auerbach Hematology Oncology Associates P C
• Collaborators: AMAG Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): February 27, 2020
• Primary Completion (Estimated): November 1, 2023
• Study Completion (Estimated): February 1, 2024

Study Registration Dates

• First Submitted: February 11, 2020
• First Submitted That Met QC Criteria: February 11, 2020
• First Posted (Actual): February 13, 2020

Study Record Updates

• Last Update Posted (Actual): June 12, 2023
• Last Update Submitted That Met QC Criteria: June 9, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Bariatric Surgery; Roux-en-Y gastric bypass (RYGB); Vertical Sleeve Gastrectomy (VSG)
• 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; Pharmaceutical Solutions; Parenteral Nutrition Solutions; Ferrosoferric Oxide
• Other Study ID Numbers: BariatricsProtocol100719

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