A Clinical Trial of Oral Versus IV Iron in Patients With Chronic Kidney Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00830037
Recruitment Status : Terminated (Terminated by the DSMB based on low chance of finding differences in mGFR slopes, but higher risk of serious adverse events in the IV iron group (aIRR = 1.60))
First Posted : January 27, 2009
Results First Posted : July 21, 2016
Last Update Posted : July 21, 2016
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
Indiana University

Brief Summary:
The long-term goal is to assess the fall in kidney function measured by glomerular filtration rate (GFR) when patients with chronic kidney disease (CKD) are exposed to intravenous iron (IVIR). We hypothesize that in subjects with mild to moderate CKD, infusion of intravenous iron (IVIR), will generate oxidative stress and cause an inflammatory response that will be associated with a more rapid decline in glomerular filtration rate (GFR) compared to oral iron.

Condition or disease Intervention/treatment Phase
Chronic Kidney Disease Iron-deficiency Anemia Drug: IV Iron Drug: Ferrous Sulfate Phase 4

Detailed Description:
Intravenous iron is commonly utilized and is likely a mechanism of renal injury in patients with CKD. This proposal will provide translational data on the role of intravenous iron to progression of kidney disease in patients with CKD. Comparison of IV iron with oral iron will allow testing the hypothesis that IVIR will generate an inflammatory response and albuminuria in the short-term, that will directly lead to a greater rate of fall in GFR, in the long-term, compared to oral iron. We hypothesize that after administration of one gram of IV iron over a course of 8 weeks, renal injury as documented by albuminuria (and fall in GFR) will be increased with IV iron sucrose therapy compared to those randomized to oral iron therapy. A randomized, parallel group, controlled trial will be performed. GFR will be measures every 6 months for two years in 200 participants by iothalamate clearances.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 136 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pathobiology of Kidney Disease: Role of Iron
Study Start Date : August 2008
Actual Primary Completion Date : November 2014

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: IV Iron Drug: IV Iron
IV iron sucrose 200 mg over 2 hours baseline visit, week 2, week 4, week 6 and week 8 for a total of 1000mg total dose. Further cycles of iv iron may be used based on periodic monitoring of iron stores.
Other Name: Venofer

Active Comparator: Oral Iron Drug: Ferrous Sulfate
Oral ferrous sulfate 325mg three times daily over 8 weeks. Further cycles of oral iron may be used based on periodic monitoring of iron stores.

Primary Outcome Measures :
  1. Mean Rate of Decline in mGFR in the Two Groups - Oral and IV Iron [ Time Frame: Baseline, 2 years ]
    Plasma clearance of iothalamate was measured by administering an IV bolus of 5 mL of iothalamate meglumine and sampling 2 mL of blood at 0, 5, 10, 20, 30, 45, 60, 90, 120, 150, 180, 240, and 300 min after injection. Iothalamate was measured by high-performance liquid chromatography. Plasma clearance was calculated using a two-pool model using validated pharmacokinetic software. The mean modeled iothalamate mGFR slope (e.g., change from baseline to 2 years) in each group (IV iron vs. oral iron) was then calculated after adjustment for baseline log urinary protein/creatinine ratio.

Secondary Outcome Measures :
  1. Proteinuria [ Time Frame: Baseline, 2 years ]
    Proteinuria was estimated using measurements of urinary protein and creatinine before iron administration at baseline and at periodic intervals thereafter. Mean change from baseline log urinary protein/creatinine ratio (g/g) is reported at 2 years.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Age greater than 18 years
  • Calculated GFR by MDRD formula < or = 60ml/min/1.73m2. We will use the MDRD formula that incorporates serum creatinine, age, race and sex, but not albumin, and blood urea nitrogen.
  • Presence of anemia and iron deficiency. Anemia will be defined as blood hemoglobin concentration <12g/dL and iron deficiency will be defined using National Kidney Foundation/Kidney Disease Outcome Quality Initiative (NFK-K/DOQI) Guidelines as serum ferritin concentration of <100ng/mL or serum transferrin saturation of <25%.

Exclusion Criteria:

  • Pregnant or breastfeeding women or women who are planning to become pregnant or those not using a reliable form of contraception (oral contraceptives, condoms, and diaphragms will be considered reliable).
  • Known hypersensitivity to iron sucrose (Venofer), iothalamate meglumine (Conray 60, Mallinckrodt) or iodine.
  • Anemia that requires RBD transfusion (Hgb <8g/dL) or may potentially need transfusion (active gastrointestinal bleeding). It would be unsafe to withdraw 150 mL blood over the study in such anemic patients.
  • Presence of acute renal failure defined as an increase in the baseline serum creatinine concentration of 0.5 mg/dl over 48 hours. This would produce oxidative stress by itself, may give unreliable rate of decline in renal function and may confound results.
  • History of IVIR use within 1 month of the study (may confound results of the study if the baseline oxidative stress is increased).
  • Evidence of iron overload (serum ferritin >800ng/nl or transferrin saturation >50%)
  • Anemia not caused by iron deficiency eg. sickle cell anemia.
  • Surgery or systemic or urinary tract infection within 1 month.
  • Organ transplant recipient or therapy with immunosuppressive agents. Nasal or inhaled corticosteroids will be permitted.

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To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00830037

United States, Indiana
VA Medical Center
Indianapolis, Indiana, United States, 46202
Sponsors and Collaborators
Indiana University
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Principal Investigator: Rajiv Agarwal, MD FASN FAHA Indiana University

Responsible Party: Indiana University Identifier: NCT00830037     History of Changes
Other Study ID Numbers: DK71633
U01DK071633 ( U.S. NIH Grant/Contract )
5U01DK071633-02 ( U.S. NIH Grant/Contract )
First Posted: January 27, 2009    Key Record Dates
Results First Posted: July 21, 2016
Last Update Posted: July 21, 2016
Last Verified: June 2016

Keywords provided by Indiana University:
kidney disease
glomerular filtration rate

Additional relevant MeSH terms:
Kidney Diseases
Renal Insufficiency, Chronic
Anemia, Iron-Deficiency
Urologic Diseases
Renal Insufficiency
Anemia, Hypochromic
Hematologic Diseases
Iron Metabolism Disorders
Metabolic Diseases
Trace Elements
Growth Substances
Physiological Effects of Drugs