Pentoxifylline and Systemic Inflammation in Hemodialysis Patients

Randomized, Double-Blinded, Controlled Clinical Trial of the Effect Pentoxifylline vs Placebo on the Serum Concentrations of TNF-a, IL-6 and CRP of Patients in Hemodialysis

The aim of this study was to compare the effect of PTX vs placebo on serum concentrations of TNF-α, IL-6, and CRP in patients on hemodialysis.

Study Overview

• Status: Completed
• Conditions: Inflammation; Hemodialysis; End-stage Renal Disease
• Intervention / Treatment: Drug: Pentoxifylline; Drug: starch tablets

Detailed Description

Patients were randomly selected from the total HD patients of our hospital. Once included, patients were randomly allocated (by a computer-generated randomization list) to a study or control group. Over a period of 4 months, patients of the study group received one PTX tablet (400 mg) orally once a day (at dinner time), whereas controls received one starch identical tablet on the same schedule.

All patients had three HD sessions per week, with the same kind of single-use dialysis membrane and dialysate. Monthly visits were scheduled for clinical and biochemical evaluations. A blood sample was taken at baseline and every month for measurement of complete blood count, urea, creatinine, glucose, albumin, lipids, and electrolytes (measured by usual methods). In serum samples at 0, 2 and 4 months, TNF-α and IL-6 concentrations were measured by ELISA using high sensitivity kits (Amersham Pharmacia Biotech, Buckinghamshire, UK). Additionally, in the same serum samples, CRP concentrations were measured by nephelometry using high sensitivity kits (Dade Behring, Marburg, Germany) in a Nephelometry Analyzer II (Dade Behring, Marburg, Germany). All laboratory measurements, including inflammation markers, were performed in the Central Laboratory (Hospital de Especialidades, CMNO), by the same personnel blinded to patient's details.

Treatment compliance was recorded by counting tablets left in the container at the end of each monthly visit.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 4

Contacts and Locations

Study Locations

• Mexico
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44320
      • Hospital de Especialidades, CMNO, IMSS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥18 years,
• ≥2 months on HD,
• arteriovenous fistula as vascular access, and
• endorsement of informed consent.

Exclusion Criteria:

• inflammatory cause of ESRD,
• liver disease, cancer, AIDS,
• any infectious disease 2 months before the study,
• failed kidney graft,
• hypersensitivity to PTX or other methylxanthines,
• hemorrhage/clotting disorders,
• risk for worsening pre-existing cardiac arrhythmias or arterial hypotension,
• treatment with antibiotics, non-steroidal anti-inflammatory drugs, steroids, immunosuppressives, statins or PTX 3 months previous to the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: placebo	Drug: starch tablets; Over a period of 4 months, patients of the control group received one starch tablet orally once a day (at dinner time); Other Names: placebo
Experimental: pentoxifylline	Drug: Pentoxifylline; Over a period of 4 months, patients of the study group received one PTX tablet (400 mg) orally once a day (at dinner time); Other Names: trental

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
serum levels of TNF-a, IL-6 and CRP	4 months

Collaborators and Investigators

• Sponsor: Coordinación de Investigación en Salud, Mexico
• Investigators: Study Chair: Alfonso M. M Cueto-Manzano, MD, MSc, PhD, Unidad de Investigación Médica en Enfermedades Renales, Hospital de Especialidades, CMNO, IMSS

Study record dates

Study Major Dates

• Study Start: January 1, 2006
• Primary Completion (Actual): May 1, 2008
• Study Completion (Actual): May 1, 2008

Study Registration Dates

• First Submitted: January 3, 2011
• First Submitted That Met QC Criteria: January 3, 2011
• First Posted (Estimate): January 4, 2011

Study Record Updates

• Last Update Posted (Actual): December 19, 2018
• Last Update Submitted That Met QC Criteria: December 18, 2018
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Keywords: inflammation; hemodialysis; pentoxifylline
• Additional Relevant MeSH Terms: Pathologic Processes; Kidney Diseases; Urologic Diseases; Renal Insufficiency; Renal Insufficiency, Chronic; Inflammation; Kidney Failure, Chronic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Enzyme Inhibitors; Platelet Aggregation Inhibitors; Protective Agents; Antioxidants; Phosphodiesterase Inhibitors; Free Radical Scavengers; Radiation-Protective Agents; Pentoxifylline
• Other Study ID Numbers: 2006-1A-I-007; Other grant (Other Grant/Funding Number: NMRC/TCR/002 - SERI/2008 - TCR 621/41/2008])