Clinical trial NCT01102218: A Safety Study of Pentoxifylline for the Treatment of Anemia
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: End Stage Renal Disease
Keywords: Anemia, ESRD
Lead sponsor: Fresenius Medical Care North America
Sponsor class: INDUSTRY
First posted: 2010-04-13
Enrollment: 48
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: 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.

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 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.

Primary outcomes:
measure: Change in Erythropoietin Dose
timeFrame: Baseline and 6 months
Secondary outcomes:
measure: Examine the EPO Resistance Index (Erythropoietin Dose/kg/Week/Hgb) or ERI Over Time
timeFrame: 6 months
measure: Observe Changes in Markers of Inflammation Including But Not Limited to TNF-α and IL-6
timeFrame: 6 months
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Fresenius Medical Care North America
state: Illinois
city: Kalamazoo
country: United States
facility: Fresenius Medical Care North America
state: Michigan
city: Brookhaven
country: United States
facility: Fresenius Medical Care North America
state: Mississippi
city: Tupelo
country: United States
facility: Fresenius Medical Care North America
state: Mississippi
city: St. Ann
country: United States
facility: Fresenius Medical Care North America
state: Missouri
city: St. Peters
country: United States
facility: Fresenius Medical Care North America
state: Missouri
city: Las Vegas
country: United States
facility: Fresenius Medical Care North America
state: Nevada
city: Columbia
country: United States
facility: Fresenius Medical Care North America
state: Tennessee
city: Irving
country: United States
facility: Fresenius Medical Care North America
state: Texas
city: Tyler
country: United States
facility: Fresenius Medical Care North America
state: Texas
Study officials:
affiliation: Fresenius Medical Care North America
name: Raymond M. Hakim, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: