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

Sponsor

Auerbach Hematology Oncology Associates P C (Other)

Overall Status

Recruiting

CT.gov ID

NCT04268849

Collaborator

AMAG Pharmaceuticals, Inc. (Industry)

104

Enrollment

Location

Arms

43.1

Anticipated Duration (Months)

2.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Iron Deficiency Anemia	Drug: Ferumoxytol Drug: Saline Drug: Ferrous sulfate tablets Drug: Vitamin C	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

104 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Double blind, double dummy of oral versus intravenous iron for iron deficiency patients after bariatric surgery. All subjects will get either oral iron and intravenous saline, or oral vitamin C and intravenous iron.Double blind, double dummy of oral versus intravenous iron for iron deficiency patients after bariatric surgery. All subjects will get either oral iron and intravenous saline, or oral vitamin C and intravenous iron.

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

Patients will wear sleep masks to blind intravenous intervention

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Feb 27, 2020

Anticipated Primary Completion Date :

Aug 1, 2023

Anticipated Study Completion Date :

Oct 1, 2023

Arms and Interventions

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

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

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

Outcome Measures

Primary Outcome Measures

Change in Clinical Global Impression - improvement scale (CGI-2) score at 6 weeks after treatment begins. [6 weeks]
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"
Change in hemoglobin concentration [6 weeks]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion criteria:

Aged ≥ 18 years
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.
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.
Willingness to participate and signing the informed consent form.

Exclusion criteria:

Iron overload or disturbances in utilization of iron (e.g. hemochromatosis and hemosiderosis)
Decompensated liver cirrhosis or active hepatitis (ALAT > 3 times upper limit of normal)
Serum ferritin > 400 ng/mL or transferrin saturation >40 %
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)
Rheumatoid arthritis with symptoms or signs of active inflammation
Pregnant and nursing women
History of multiple allergies (two or more)
Known hypersensitivity to ferumoxytol or oral iron or any excipients in the drug products
Previous IV iron treatment for IDA
Other iron treatment or blood transfusion within 4 weeks prior to the screening or treatment visit
Planned elective surgery during the study
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