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

NCT00830037 | Terminated Phase 4 Results DMC

• 3 other identifiers: DK71633U01DK0716335U01DK071633-02
• Study Type: interventional
• Target: 136
• Locations: 1 country
• Sites: 1

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.

Conditions

Chronic Kidney Disease; Iron-deficiency Anemia

Keywords

anemia; iron; kidney disease; progression; glomerular filtration rate

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline, 2 years

Secondary Outcomes (1)

• Proteinuria

  Baseline, 2 years

Study Arms (2)

IV Iron

EXPERIMENTAL

Drug: IV Iron

Oral Iron

ACTIVE COMPARATOR

Drug: Ferrous Sulfate

Interventions

IV Iron DRUG

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.

Also known as: Venofer

IV Iron

Ferrous Sulfate DRUG

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.

Oral Iron

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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%.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Indiana University: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

VA Medical Center

Indianapolis, Indiana, 46202, United States

Location

MeSH Terms

Conditions

Renal Insufficiency, Chronic; Anemia, Iron-Deficiency; Anemia; Kidney Diseases; Disease Progression

Interventions

ferryl iron; Ferric Oxide, Saccharated; ferrous sulfate

Condition Hierarchy (Ancestors)

Renal Insufficiency; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Anemia, Hypochromic; Hematologic Diseases; Hemic and Lymphatic Diseases; Iron Deficiencies; Iron Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Ferric Compounds; Iron Compounds; Inorganic Chemicals; Glucaric Acid; Sugar Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Hydroxy Acids; Carbohydrates

Results Point of Contact

• Title: Rajiv Agarwal, MD, FAHA, FASN, FASH
• Organization: Indiana University School of Medicine & Richard L Roudebush VA Medical Center

ragarwal@iu.edu

317-988-2241

Study Officials

• Rajiv Agarwal, MD FASN FAHA

  Indiana University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 26, 2009
• First Posted: January 27, 2009
• Study Start: August 1, 2008
• Primary Completion: November 1, 2014
• Last Updated: July 21, 2016
• Results First Posted: July 21, 2016

Record last verified: 2016-06

Locations

US (1)