Ignite Creation Date:
2024-05-06 @ 1:29 AM
Last Modification Date:
2024-10-26 @ 11:04 AM
Study NCT ID:
NCT01820897
Status:
COMPLETED
Last Update Posted:
2015-03-26
First Post:
2013-03-26
Brief Title:
Efficacy of Fosfomycin-Trometamol in Urinary Tract Infection Prophylaxis After Kidney Transplantation
Sponsor:
JOSE MANUEL ARREOLA GUERRA
Organization:
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Study Overview
Official Title:
Fosfomycin-Trometamol in Urinary Tract Infection Prophylaxis After Kidney Transplantation Randomized Controlled Trial
Status:
COMPLETED
Status Verified Date:
2015-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Urinary tract infections UTI are the most common complications after kidney transplantation Most series have reported incidence between 20 to 50 during the first year In the most recent report from our center the incidence was 366 during the first 6 months after transplantation
The clinical consequence in the graft survival and the association with immunological rejection has not been well defined Nevertheless the association of UTI with high rate of hospitalization and their costs are widely recognized There is paucity of trials specially randomized and controlled comparing antibiotic prophylaxis in this group of patients In a recently published metaanalysis Green et al Transpl Infect Dis 2011 Oct135441-7 found only 6 clinical trials well designed the conclusion was that antibiotic prophylaxis reduced the incidence of UTI and the risk of sepsis Based in this information the KDIGO guidelines in transplantation recommend the prophylaxis for UTI with sulfamethoxazole-trimethoprim SMT Nevertheless the rate of bacterial resistance to SMT has been reported above 50 in almost all the series
Fosfomycin-trometamol FT is a wall antibiotic piruvil-tranferase inhibitor that has shown a good bioavailability especially in the urinary tract It has shown a wide antibacterial spectrum but the important target seems to be enteric bacilli particularly Escherichia coli the most prevalent cause of UTI FT has also shown a very good activity against E coli producer of Extended Spectrum Betalactamases Recently the rate of these multi-drug resistant bacteria has increased in our center as evidence of worldwide distribution In addition the rate of FT resistance has been stable during the last years 3 This phenomenon could be explained because of the properties of this antibiotic the most important one seems to be related with the unique mechanism of action and the lack to propagate the mechanisms of resistance at least in E coli There is only one clinical trial randomized and controlled which compared FT with placebo in UTI prophylaxis 317 women with recurrent UTI three by year were included They found rates of 014 and 29 episodespatientyear respectively p0001 Furthermore there was no FT resistance during the follow up
Our hypothesis is that in the first six months after kidney transplantation UTI prophylaxis with FT will show greater efficacy in comparison with SMT Considering the incidence of UTI in our center 366 and the rate of UTI in the unique trial of prophylaxis with FT 14 65 patients will be needed by group of treatment to demonstrate a difference of 22 in the incidence of UTI with a power of 80 and confidence level of 95 The primary outcome is the incidence and rate of UTI during the first six months after kidney transplantation The secondary outcomes are the hospitalization rate antibiotic resistance rate rejections and titer and number of de novo donor specific antibodies
The investigators propose a randomized double blind placebo controlled trial to compare FT with SMT in the efficacy and safety to prevent UTI during the first six months after kidney transplantation The investigators will include patients from two tertiary-care transplant centers Recruiting and the randomization will be carried out separately by center and gender because female patients have a greater risk of UTI The medical visits will be scheduled monthly and include general laboratory urine culture and information gathering about antibiotic side effects as well as adherence Rejection rate and the number and titers of de novo donor specific antibodies secondary outcome will be obtained according to the standard of care of the institutional kidney transplantation follow up These include kidney biopsy at days 0 and 90 after transplantation as well as determination of donor specific antibodies after sixth months of follow up Graft biopsy is also performed whenever graft dysfunction exists in the absence of an identifiable cause infection urinary graft obstruction
The clinical consequence in the graft survival and the association with immunological rejection has not been well defined Nevertheless the association of UTI with high rate of hospitalization and their costs are widely recognized There is paucity of trials specially randomized and controlled comparing antibiotic prophylaxis in this group of patients In a recently published metaanalysis Green et al Transpl Infect Dis 2011 Oct135441-7 found only 6 clinical trials well designed the conclusion was that antibiotic prophylaxis reduced the incidence of UTI and the risk of sepsis Based in this information the KDIGO guidelines in transplantation recommend the prophylaxis for UTI with sulfamethoxazole-trimethoprim SMT Nevertheless the rate of bacterial resistance to SMT has been reported above 50 in almost all the series
Fosfomycin-trometamol FT is a wall antibiotic piruvil-tranferase inhibitor that has shown a good bioavailability especially in the urinary tract It has shown a wide antibacterial spectrum but the important target seems to be enteric bacilli particularly Escherichia coli the most prevalent cause of UTI FT has also shown a very good activity against E coli producer of Extended Spectrum Betalactamases Recently the rate of these multi-drug resistant bacteria has increased in our center as evidence of worldwide distribution In addition the rate of FT resistance has been stable during the last years 3 This phenomenon could be explained because of the properties of this antibiotic the most important one seems to be related with the unique mechanism of action and the lack to propagate the mechanisms of resistance at least in E coli There is only one clinical trial randomized and controlled which compared FT with placebo in UTI prophylaxis 317 women with recurrent UTI three by year were included They found rates of 014 and 29 episodespatientyear respectively p0001 Furthermore there was no FT resistance during the follow up
Our hypothesis is that in the first six months after kidney transplantation UTI prophylaxis with FT will show greater efficacy in comparison with SMT Considering the incidence of UTI in our center 366 and the rate of UTI in the unique trial of prophylaxis with FT 14 65 patients will be needed by group of treatment to demonstrate a difference of 22 in the incidence of UTI with a power of 80 and confidence level of 95 The primary outcome is the incidence and rate of UTI during the first six months after kidney transplantation The secondary outcomes are the hospitalization rate antibiotic resistance rate rejections and titer and number of de novo donor specific antibodies
The investigators propose a randomized double blind placebo controlled trial to compare FT with SMT in the efficacy and safety to prevent UTI during the first six months after kidney transplantation The investigators will include patients from two tertiary-care transplant centers Recruiting and the randomization will be carried out separately by center and gender because female patients have a greater risk of UTI The medical visits will be scheduled monthly and include general laboratory urine culture and information gathering about antibiotic side effects as well as adherence Rejection rate and the number and titers of de novo donor specific antibodies secondary outcome will be obtained according to the standard of care of the institutional kidney transplantation follow up These include kidney biopsy at days 0 and 90 after transplantation as well as determination of donor specific antibodies after sixth months of follow up Graft biopsy is also performed whenever graft dysfunction exists in the absence of an identifiable cause infection urinary graft obstruction
Detailed Description:
None
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None