Back to resultsA Clinical Trial of Oral Versus IV Iron in Patients With Chronic Kidney Disease
Primary Purpose
Chronic Kidney Disease, Iron-deficiency Anemia
Status
Terminated
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
IV Iron
Ferrous Sulfate
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Kidney Disease focused on measuring anemia, iron, kidney disease, progression, glomerular filtration rate
Eligibility 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.
Sites / Locations
- VA Medical Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
IV Iron
Oral Iron
Arm Description
Outcomes
Primary Outcome Measures
Mean Rate of Decline in mGFR in the Two Groups - Oral and IV Iron
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
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.
Full Information
NCT ID
NCT00830037
First Posted
January 26, 2009
Last Updated
June 9, 2016
Sponsor
Indiana University
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
1. Study Identification
Unique Protocol Identification Number
NCT00830037
Brief Title
A Clinical Trial of Oral Versus IV Iron in Patients With Chronic Kidney Disease
Official Title
Pathobiology of Kidney Disease: Role of Iron
Study Type
Interventional
2. Study Status
Record Verification Date
June 2016
Overall Recruitment Status
Terminated
Why Stopped
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)
Study Start Date
August 2008 (undefined)
Primary Completion Date
November 2014 (Actual)
Study Completion Date
undefined (undefined)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Indiana University
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Kidney Disease, Iron-deficiency Anemia
Keywords
anemia, iron, kidney disease, progression, glomerular filtration rate
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
136 (Actual)
8. Arms, Groups, and Interventions
Arm Title
IV Iron
Arm Type
Experimental
Arm Title
Oral Iron
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
IV Iron
Other Intervention Name(s)
Venofer
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Ferrous Sulfate
Intervention Description
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 Measure Information:
Title
Mean Rate of Decline in mGFR in the Two Groups - Oral and IV Iron
Description
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.
Time Frame
Baseline, 2 years
Secondary Outcome Measure Information:
Title
Proteinuria
Description
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.
Time Frame
Baseline, 2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Rajiv Agarwal, MD FASN FAHA
Organizational Affiliation
Indiana University
Official's Role
Principal Investigator
Facility Information:
Facility Name
VA Medical Center
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
12. IPD Sharing Statement
Learn more about this trial
A Clinical Trial of Oral Versus IV Iron in Patients With Chronic Kidney Disease
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