A Safety Study of Pentoxifylline for the Treatment of Anemia

This study has been terminated.
(Lack of statistical difference between both arms of the trial.)
Sponsor:
Information provided by (Responsible Party):
Fresenius Medical Care North America
ClinicalTrials.gov Identifier:
NCT01102218
First received: April 9, 2010
Last updated: March 26, 2012
Last verified: March 2012
  Purpose

Chronic kidney disease (CKD) patients have increased levels of inflammation and oxidative stress, which in turn contribute to anemia and cardiovascular disease.

Pentoxifylline is known to have anti-inflammatory and anti-oxidant properties, and has shown promise in improving the treatment of patients with anemia. This study will examine the use of pentoxifylline for the treatment of anemia in chronic kidney disease.


Condition Intervention Phase
End Stage Renal Disease
Drug: Erythropoietin
Drug: Pentoxifylline
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Multi-Center Study to Determine the Safety and Efficacy of Erythropoietin Plus Pentoxifylline Versus Erythropoietin Alone for the Treatment of Anemia in Subjects With End Stage Renal Disease on Maintenance Hemodialysis

Resource links provided by NLM:


Further study details as provided by Fresenius Medical Care North America:

Primary Outcome Measures:
  • Change in Erythropoietin Dose [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: No ]
    Erythropoietin dose is amount needed to maintain a hemoglobin between 11 and 12 mg/dL.


Secondary Outcome Measures:
  • Examine the EPO Resistance Index (Erythropoietin Dose/kg/Week/Hgb) or ERI Over Time [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • Observe Changes in Markers of Inflammation Including But Not Limited to TNF-α and IL-6 [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Enrollment: 48
Study Start Date: August 2010
Study Completion Date: January 2012
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: erythropoietin plus pentoxifylline Drug: Erythropoietin
Standard of Care
Drug: Pentoxifylline
400 mg qd po for 6 months
Other Name: brand name is Trental
Active Comparator: erythropoietin alone Drug: Erythropoietin
Standard of Care

Detailed Description:

Treatment of the anemia of renal failure has been revolutionized by the use of erythropoietin and other ESAs (erythropoiesis-stimulating agent). Concerns with ESA use include a substantial number of End Stage Renal Disease (ESRD) patients with ESA-resistant anemia, and a growing body of evidence of potential negative effects of high doses of ESA use, including increased mortality and increased rate of tumor growth in cancer patients.

There are only a couple of small studies in the literature examining the effects of pentoxifylline on anemia in patients with renal failure. The results are limited by the very small number of patients. There is clearly a need for a larger, prospective, clinical trial of pentoxifylline in ESRD patients, not limited to those with ESA-resistant anemia. This would be the first prospective, randomized clinical trial of this size to study pentoxifylline for the treatment of anemia in chronic kidney disease.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female, aged ≥18 years;
  • Able to comply with the study procedures and medication;
  • Written informed consent given;
  • On a stable in-center hemodialysis regimen (at least 3 times per week) for ≥ 12 weeks prior to screening;
  • Subject must have been on a stable (< 25% change) erythropoietin dose with an average of ≥ 15,000 and <55,000 units/week of treatment for ≥ 14 days prior to screening visit;
  • Two hemoglobin measurements must meet the following criteria: (1) Taken ≥ 2 weeks apart; (2) Between 10 and 12 g/dL, inclusive; (3) Within 1 g/dL of each other; and (4) Occurred within 30 days prior to screening visit;
  • If subject is a female and of childbearing potential (pre-menopausal and not surgically sterile), subject is willing to use an effective contraceptive method throughout study, which includes abstinence, barrier methods, hormones, or IUDs;
  • Life expectancy of 12 months or greater;
  • Most recent single pool Kt/V ≥1.2, taken within 45 days prior to screening visit;
  • Stable nutrition status with all albumin levels ≥ 3.0 g/dL within the 30 days prior to screening visit.

Exclusion Criteria:

  • Participation in any clinical trial using an investigational product or device during the 30 days preceding the Screening Visit;
  • Currently undergoing nocturnal hemodialysis;
  • A significant history of alcohol, drug or solvent abuse in the opinion of the investigator;
  • Serum iPTH > 800 pg/mL within 90 days prior to screening visit;
  • Dysrhythmia or severe cardiac disease: CHF Class III-IV; unstable cardiovascular diagnosis (for example MI, CABG, PTCA, CVA, and TIA) within 90 days prior to screening visit;
  • Significant concurrent liver disorder [Aspartate transaminase (AST) or alanine transaminase (ALT) values > 3 times upper limit of normal (ULN) within 30 days prior to screening];
  • Platelet count < 130x109 within 30 days prior to screening visit or on the day of the screening visit;
  • Known hypersensitivity to, or intolerance of, Pentoxifylline or other methylxanthines, such as caffeine, theophylline or theobromine;
  • Currently taking pentoxifylline, warfarin, theophylline, aminophylline, dyphylline, or oxtriphylline;
  • Absolute or functional iron deficiency [transferrin saturation (TSAT) <20%] within 45 days prior to screening;
  • Recent or severe hemorrhage per PI discretion;
  • Significant bleeding episode or prolonged bleeding from dialysis access per PI judgment within the 3 months prior to screening;
  • Melatonin treatment, androgen therapy or blood transfusion within 30 days prior to screening;
  • Vitamin C therapy at dose greater than 100 mg/day or at a dose which has changed within the last 3 months;
  • Current active cancer (excluding basal cell carcinoma of the skin);
  • Poorly controlled hypertension per PI judgment within 4 weeks prior to screening;
  • Known HIV positive status;
  • Significant GI disorders where absorption of an oral medication might, in the opinion of the Investigator, be impaired;
  • Anticipated live donor kidney transplant or any other planned major surgery over the study duration;
  • History of poor adherence to hemodialysis or medical regimen;
  • Any active clinically significant infection or evidence of an underlying infection;
  • Currently on immunosuppressive drug regimen other than a stable, low dose of steroids, per PI judgment;
  • Any disease or condition, physical or psychological that, in the opinion of the investigator, would compromise the safety of the subject or the likelihood of achieving reliable results or increase the likelihood of the subject being withdrawn.
  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: NCT01102218

Locations
United States, Illinois
Fresenius Medical Care North America
Chicago, Illinois, United States, 60616
United States, Michigan
Fresenius Medical Care North America
Kalamazoo, Michigan, United States, 49007
United States, Mississippi
Fresenius Medical Care North America
Brookhaven, Mississippi, United States, 39601
Fresenius Medical Care North America
Tupelo, Mississippi, United States, 38801
United States, Missouri
Fresenius Medical Care North America
St. Ann, Missouri, United States, 63074
Fresenius Medical Care North America
St. Peters, Missouri, United States, 63376
United States, Nevada
Fresenius Medical Care North America
Las Vegas, Nevada, United States, 89120
United States, Tennessee
Fresenius Medical Care North America
Columbia, Tennessee, United States, 38478
United States, Texas
Fresenius Medical Care North America
Irving, Texas, United States, 75039
Fresenius Medical Care North America
Tyler, Texas, United States, 75701
Sponsors and Collaborators
Fresenius Medical Care North America
Investigators
Principal Investigator: Raymond M. Hakim, MD, PhD Fresenius Medical Care North America
  More Information

No publications provided

Responsible Party: Fresenius Medical Care North America
ClinicalTrials.gov Identifier: NCT01102218     History of Changes
Other Study ID Numbers: 2010-01
Study First Received: April 9, 2010
Results First Received: January 18, 2012
Last Updated: March 26, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Fresenius Medical Care North America:
Anemia, ESRD

Additional relevant MeSH terms:
Kidney Diseases
Kidney Failure, Chronic
Urologic Diseases
Renal Insufficiency, Chronic
Renal Insufficiency
Pentoxifylline
Epoetin alfa
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Platelet Aggregation Inhibitors
Hematologic Agents
Therapeutic Uses
Radiation-Protective Agents
Protective Agents
Physiological Effects of Drugs
Vasodilator Agents
Cardiovascular Agents
Free Radical Scavengers
Antioxidants
Hematinics

ClinicalTrials.gov processed this record on October 02, 2014