Clinical trial NCT00830037: 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
Overall status: TERMINATED
Phase: PHASE4
Conditions: Chronic Kidney Disease
Iron-deficiency Anemia
Keywords: anemia
iron
kidney disease
progression
glomerular filtration rate
Lead sponsor: Indiana University
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2009-01-27
Enrollment: 136
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Mean Rate of Decline in mGFR in the Two Groups - Oral and IV Iron
timeFrame: Baseline, 2 years
Secondary outcomes:
measure: Proteinuria
timeFrame: Baseline, 2 years
Other outcomes:
Locations:
city: Indianapolis
country: United States
facility: VA Medical Center
state: Indiana
Study officials:
affiliation: Indiana University
name: Rajiv Agarwal, MD FASN FAHA
role: PRINCIPAL_INVESTIGATOR
References: