The Effect of Antimicrobial Therapy on the Serum Level of P-cresol in Peritoneal Dialysis Patients

NCT00433342 | Terminated Phase 1

• 1 other identifier: ML3532
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

An important subgroup of protein-bound toxins are generated as a result of protein fermentation in the colon. P-cresol is a fermentation metabolite of tyrosine. In renal failure, the colonic generation rate of p-cresol is markedly elevated. After absorption, the majority of p-cresol is conjugated to form p-cresyl sulphate. There is clear evidence, both in vitro and in vivo, that accumulation of conjugated fermentation metabolites is correlated with clinical important endpoints. Free p-cresol is an independent predictor for mortality in hemodialysis patients. Moreover, in renal failure patients, neither hemodialysis nor peritoneal dialysis is capable of normalising the clearly elevated serum concentrations of p-cresyl sulphate. Removal is at least partially diminished by the important protein binding of p-cresol. Besides adaptation of renal replacement therapies to improve removal of protein bound solutes, another approach is to lower the generation of uremic toxins. The mechanisms underlying colonic carbohydrate and protein fermentation, responsible for the generation of p-cresol, are only partially understood. On the one hand, the ratio of fermentable carbohydrates to proteins has been shown to be an important determinant of protein fermentation. On the other hand, changes in the colonic bacterial flora influence the generation of p-cresol in dogs and in healthy human individuals. The effect of antibiotic therapy on bacterial protein fermentation and thus on the generation of p-cresol is not known. A reanalysis of data abstracted from a recent longitudinal study in peritoneal dialysis (PD) patients suggests that antibiotic therapy may lower p-cresol levels substantially. The current study aims at confirming these data in a prospective manner.

Conditions

Chronic Kidney Disease

Keywords

Antibiotic; p-cresol; peritoneal dialysis

Outcome Measures

Primary Outcomes (1)

• p-cresol reduction rate

  8 weeks

Study Arms (2)

I

EXPERIMENTAL

Flucloxacillin

Drug: Flucloxacillin

II

NO INTERVENTION

Interventions

Flucloxacillin DRUG

500 mg QD oral

Also known as: Floxapen

I

Eligibility Criteria

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

You may qualify if:

• Age \> 18
• Exit site infection, requiring antibiotic treatment
• Maintenance therapy with peritoneal dialysis

You may not qualify if:

• Signs of peritonitis

Sponsors & Collaborators

• Universitaire Ziekenhuizen KU Leuven: lead

Study Sites (1)

Universitaire Ziekenhuizen Leuven

Leuven, Vlaams-Brabant, 3000, Belgium

Location

Related Publications (1)

• Bammens B, Evenepoel P, Keuleers H, Verbeke K, Vanrenterghem Y. Free serum concentrations of the protein-bound retention solute p-cresol predict mortality in hemodialysis patients. Kidney Int. 2006 Mar;69(6):1081-7. doi: 10.1038/sj.ki.5000115.

  PMID: 16421516 BACKGROUND

MeSH Terms

Conditions

Renal Insufficiency, Chronic

Interventions

Floxacillin

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; 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

Intervention Hierarchy (Ancestors)

Cloxacillin; Oxacillin; Penicillins; beta-Lactams; Lactams; Amides; Organic Chemicals; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Björn Meijers, MD

  UZ Leuven

  STUDY CHAIR

• Pieter Evenepoel, MD, PhD

  UZ Leuven

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr.

Study Record Dates

• First Submitted: February 7, 2007
• First Posted: February 9, 2007
• Study Start: March 1, 2006
• Primary Completion: April 1, 2020
• Study Completion: April 1, 2020
• Last Updated: April 27, 2020

Record last verified: 2020-04

Locations

BE (1)