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

This study has been 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))
Sponsor:
Collaborator:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
Indiana University
ClinicalTrials.gov Identifier:
NCT00830037
First received: January 26, 2009
Last updated: June 9, 2016
Last verified: June 2016
  Purpose
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 Intervention Phase
Chronic Kidney Disease
Iron-deficiency Anemia
Drug: IV Iron
Drug: Ferrous Sulfate
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pathobiology of Kidney Disease: Role of Iron

Resource links provided by NLM:


Further study details as provided by Indiana University:

Primary Outcome Measures:
  • Mean Rate of Decline in mGFR in the Two Groups - Oral and IV Iron [ Time Frame: Baseline, 2 years ] [ Designated as safety issue: Yes ]
    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:
  • Proteinuria [ Time Frame: Baseline, 2 years ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 136
Study Start Date: August 2008
Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00830037

Locations
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)
Investigators
Principal Investigator: Rajiv Agarwal, MD FASN FAHA Indiana University
  More Information

Responsible Party: Indiana University
ClinicalTrials.gov Identifier: NCT00830037     History of Changes
Other Study ID Numbers: DK71633  U01DK071633  5U01DK071633-02 
Study First Received: January 26, 2009
Results First Received: April 28, 2016
Last Updated: June 9, 2016
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Keywords provided by Indiana University:
anemia
iron
kidney disease
progression
glomerular filtration rate

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

ClinicalTrials.gov processed this record on July 28, 2016