- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04333602
Asymptomatic Bacteriuria in Early Kidney Transplantation Follow up
Screening and Treatment of Asymptomatic Bacteriuria in the First Two Months After Kidney Transplant. Randomized Control Trial
Study Overview
Status
Intervention / Treatment
Detailed Description
I. Background Urinary tract infection (UTI) is the most frequent infectious complication in renal transplant recipients (RTR) during the first year, reaching an incidence from 23% to 75%. (1,2) Asymptomatic bacteriuria (AB) and UTI are associated with graft pyelonephritis, sepsis, acute rejection, and long-term graft dysfunction. (3-5) Recently, recurrent UTI episodes have been reported to be associated with poorer patient and graft survival compared to those without recurrent infection. (6) Risk factors are classified as: patient-related (diabetes mellitus, anatomical abnormalities of the urinary tract) and transplant-related (type of immunosuppression, time of the bladder catheter (UC) and double J stent. (7,8) The recommendations of the clinical guidelines suggest prophylaxis with trimethoprim / sulfamethoxazole (TMP / SMX) 160/800 mg every 24 hr during the first 6 months after kidney transplant (KT) ( 9).
The incidence of UTI in RTR has remained between 30 and 36% despite TMP / SMX antimicrobial prophylaxis (7) in a third-level care center in Mexico City; This high incidence is explained in part by the high resistance rate to TMP / SMX (> 80%) in clinical isolates of Escherichia coli recovered from urine both in Mexico and other regions of the world, a condition that discourages its continued use as a prophylactic agent from UTI. (10-12) Given this problem, a clinical trial of kidney transplant recipients was started, comparing the usual prophylaxis with TMP / SMX vs Phosphomycin 3 grams every 10 days for 6 months. The study was suspended prematurely due to therapeutic futility (19). A new clinical trial was performed using intravenous phosphomycin disodium the day of the transplant, prior to the removal of the bladder catheter and the double J ureteral stent. In this study, the intervention group presented a lower incidence of UTI (7.3 vs. 36.6%, p = 0.001).
In both previously described trials, patients underwent UTI screening by urine culture on specific days. Asymptomatic bacteriuria episodes are treated according to the susceptibility of the germ. This alone represents a strategy to decrease the incidence of UTI. Treatment of AB episodes has clearly not been shown to be beneficial in this group of patients. Recently in a controlled clinical trial no benefit was found in KTR with screening and treatment of AB after the second month of post KT. (14) This study partially supports the recommendations of clinical practice of the American Society of Infectious Diseases, where the systematic scrutiny and treatment of the UTI in kidney transplantation is mentioned as not recommended, however the authors propose possible benefit during the first month after KT. (2) II. Definition of the problem Urinary tract infection is the most frequent infectious complication after KT. The systematic screening and treatment of AB during the first months after transplantation is controversial. Given the increase in bacterial resistance, it is important to limit the exposure of antibiotics in high-risk groups. Various studies have demonstrated the utility of the administration of antimicrobial prophylaxis during the first months after transplantation for the reduction of UTI and AB events. However, these studies and several centers carry out systematic scrutiny of UTI with treatment of episodes of AB. Recently a controlled clinical trial showed that the scrutiny and treatment of AB after the second month after transplantation is not useful.
III. Justification UTI represents the most frequent cause of post kidney transplant infection. AB is highly prevalent during the first months after KT. Its prevalence during the first trimester is high and currently the treatment of AB is not fully justified. Due to the need to avoid the abuse of antibiotics in our setting, it is necessary to evaluate the usefulness of screening and treatment of AB in the first 8 weeks post KT. The Medical Center where the trial will be done, performs an average of 100 to 120 kidney transplants annually, which makes the clinical trial feasible.
IV. Hypothesis The screening and treatment of AB during the first 2 months will reduce the incidence of UTI, pyelonephritis and hospitalizations by 50% (composite outcome).
V. Objectives. To assess the efficacy of AB screening and treatment in KT recipients during the first two months post KT.
To assess the incidence of UTI, pyelonephritis and hospitalizations associated with UTI Assess the prevalence of multi-resistant germs The urine culture samples will be labeled and in case of being positive, the isolated strain will be conserved for the subsequent identification of virulence genes. Said strain will be identified with the record of the study of the patient, in order to know the clinical variables of the time of obtaining said sample.
VIII. Definition of monitoring variables Asymptomatic Bacteriuria: In the case of men, medium stream urine culture with isolation of > 1 x 105 colonies. In the case of women, medium-stream urine culture with isolation of > 1 x 105 colonies (2 cultures), must be the same germ.
Urinary tract infection: Isolation of medium stream urine culture >1 x 104 colonies coupled with symptoms such as fever, dysuria, leukocyturia or positive nitrites. If it is only fever, another infectious focus should be ruled out.
Pyelonephritis: Urinary tract infection coupled with fever, graft pain, systemic inflammatory response, or shock. It should not have another concomitant infection.
X. Sample Size:
Taking into account that UTI events occur on average 30% during the first 3 months after KT if the investigators want to reduce events to 10%. Taking the proportions formula. The sample required to be included is 62 patients per maneuver group.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
-
Aguascalientes, Mexico, 20230
- Jose Manuel Arreola
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
- Older Adult
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Kidney transplant candidates scheduled for the procedure
Exclusion Criteria:
- Patients with urological complications that did not have a bladder catheter and/or double J ureteral stent removed during the study period.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Screening and Treatment of Asymptomatic Bacteriruria
All patients assigned to this arm will be screen with urine culture: post- bladder catheter removal, three weeks post-transplant and before double-J ureteral stent removal.
If we detect asymptomatic bacteriuria specific treatment will be instituted.
|
Urinary culture: post- bladder catheter removal, three weeks post-transplant and before double-J ureteral stent removal.
Based in the assigned group If we detect asymptomatic bacteriuria specific treatment will be instituted or No treatment.
Other Names:
|
No Intervention: Screening and NO treatment of Asymptomatic Bacteriuria
All patients assigned to this arm will be screen with urine culture: post- bladder catheter removal, three weeks post-transplant and before double-J ureteral stent removal.
No treatment will be instituted.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of symptomatic urinary tract infection
Time Frame: Two months
|
urinary symptoms associated with positive urine culture
|
Two months
|
Time to the first symptomatic urinary tract infection
Time Frame: Two moths
|
urinary symptoms associated with positive urine culture
|
Two moths
|
Incidence of pyelonephritis or hospitalization related to urinary tract infection
Time Frame: Two months
|
Two months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Bacterial virulence genes related to urinary tract infection
Time Frame: Two moths
|
E. Coli and Klebsiella.
sp virulence genes will be analysed
|
Two moths
|
Collaborators and Investigators
Publications and helpful links
General Publications
- Magiorakos AP, Srinivasan A, Carey RB, Carmeli Y, Falagas ME, Giske CG, Harbarth S, Hindler JF, Kahlmeter G, Olsson-Liljequist B, Paterson DL, Rice LB, Stelling J, Struelens MJ, Vatopoulos A, Weber JT, Monnet DL. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect. 2012 Mar;18(3):268-81. doi: 10.1111/j.1469-0691.2011.03570.x. Epub 2011 Jul 27.
- Kidney Disease: Improving Global Outcomes (KDIGO) Transplant Work Group. KDIGO clinical practice guideline for the care of kidney transplant recipients. Am J Transplant. 2009 Nov;9 Suppl 3:S1-155. doi: 10.1111/j.1600-6143.2009.02834.x.
- Lee JR, Bang H, Dadhania D, Hartono C, Aull MJ, Satlin M, August P, Suthanthiran M, Muthukumar T. Independent risk factors for urinary tract infection and for subsequent bacteremia or acute cellular rejection: a single-center report of 1166 kidney allograft recipients. Transplantation. 2013 Oct 27;96(8):732-8. doi: 10.1097/TP.0b013e3182a04997.
- Britt NS, Hagopian JC, Brennan DC, Pottebaum AA, Santos CAQ, Gharabagi A, Horwedel TA. Effects of recurrent urinary tract infections on graft and patient outcomes after kidney transplantation. Nephrol Dial Transplant. 2017 Oct 1;32(10):1758-1766. doi: 10.1093/ndt/gfx237.
- Sorto R, Irizar SS, Delgadillo G, Alberu J, Correa-Rotter R, Morales-Buenrostro LE. Risk factors for urinary tract infections during the first year after kidney transplantation. Transplant Proc. 2010 Jan-Feb;42(1):280-1. doi: 10.1016/j.transproceed.2009.11.029.
- de Souza RM, Olsburgh J. Urinary tract infection in the renal transplant patient. Nat Clin Pract Nephrol. 2008 May;4(5):252-64. doi: 10.1038/ncpneph0781. Epub 2008 Mar 11.
- Kawecki D, Kwiatkowski A, Sawicka-Grzelak A, Durlik M, Paczek L, Chmura A, Mlynarczyk G, Rowinski W, Luczak M. Urinary tract infections in the early posttransplant period after kidney transplantation: etiologic agents and their susceptibility. Transplant Proc. 2011 Oct;43(8):2991-3. doi: 10.1016/j.transproceed.2011.09.002.
- Origuen J, Fernandez-Ruiz M, Lopez-Medrano F, Ruiz-Merlo T, Gonzalez E, Morales JM, Fiorante S, San-Juan R, Villa J, Orellana MA, Andres A, Aguado JM. Progressive increase of resistance in Enterobacteriaceae urinary isolates from kidney transplant recipients over the past decade: narrowing of the therapeutic options. Transpl Infect Dis. 2016 Aug;18(4):575-84. doi: 10.1111/tid.12547. Epub 2016 Jul 4.
- Falagas ME, Kastoris AC, Kapaskelis AM, Karageorgopoulos DE. Fosfomycin for the treatment of multidrug-resistant, including extended-spectrum beta-lactamase producing, Enterobacteriaceae infections: a systematic review. Lancet Infect Dis. 2010 Jan;10(1):43-50. doi: 10.1016/S1473-3099(09)70325-1.
- Origuen J, Lopez-Medrano F, Fernandez-Ruiz M, Polanco N, Gutierrez E, Gonzalez E, Merida E, Ruiz-Merlo T, Morales-Cartagena A, Perez-Jacoiste Asin MA, Garcia-Reyne A, San Juan R, Orellana MA, Andres A, Aguado JM. Should Asymptomatic Bacteriuria Be Systematically Treated in Kidney Transplant Recipients? Results From a Randomized Controlled Trial. Am J Transplant. 2016 Oct;16(10):2943-2953. doi: 10.1111/ajt.13829. Epub 2016 May 23.
- Nicolle LE, Bradley S, Colgan R, Rice JC, Schaeffer A, Hooton TM; Infectious Diseases Society of America; American Society of Nephrology; American Geriatric Society. Infectious Diseases Society of America guidelines for the diagnosis and treatment of asymptomatic bacteriuria in adults. Clin Infect Dis. 2005 Mar 1;40(5):643-54. doi: 10.1086/427507. Epub 2005 Feb 4. No abstract available. Erratum In: Clin Infect Dis. 2005 May 15;40(10):1556.
- Bauer MP, Kuijper EJ, van Dissel JT; European Society of Clinical Microbiology and Infectious Diseases. European Society of Clinical Microbiology and Infectious Diseases (ESCMID): treatment guidance document for Clostridium difficile infection (CDI). Clin Microbiol Infect. 2009 Dec;15(12):1067-79. doi: 10.1111/j.1469-0691.2009.03099.x.
- Arreola-Guerra JM, Rosado-Canto R, Alberu J, Maravilla E, Torres-Gonzalez P, Criollo E, Perez M, Mancilla E, Arvizu M, Morales-Buenrostro LE, Vilatoba-Chapa M, Sifuentes-Osornio J. Fosfomycin trometamol in the prophylaxis of post-kidney transplant urinary tract infection: A controlled, randomized clinical trial. Transpl Infect Dis. 2018 Oct;20(5):e12980. doi: 10.1111/tid.12980. Epub 2018 Sep 10.
- Alangaden GJ, Thyagarajan R, Gruber SA, Morawski K, Garnick J, El-Amm JM, West MS, Sillix DH, Chandrasekar PH, Haririan A. Infectious complications after kidney transplantation: current epidemiology and associated risk factors. Clin Transplant. 2006 Jul-Aug;20(4):401-9. doi: 10.1111/j.1399-0012.2006.00519.x.
- Parasuraman R, Julian K; AST Infectious Diseases Community of Practice. Urinary tract infections in solid organ transplantation. Am J Transplant. 2013 Mar;13 Suppl 4:327-36. doi: 10.1111/ajt.12124. No abstract available.
- Fiorante S, Lopez-Medrano F, Lizasoain M, Lalueza A, Juan RS, Andres A, Otero JR, Morales JM, Aguado JM. Systematic screening and treatment of asymptomatic bacteriuria in renal transplant recipients. Kidney Int. 2010 Oct;78(8):774-81. doi: 10.1038/ki.2010.286. Epub 2010 Aug 18.
- Golebiewska JE, Debska-Slizien A, Rutkowski B. Treated asymptomatic bacteriuria during first year after renal transplantation. Transpl Infect Dis. 2014 Aug;16(4):605-15. doi: 10.1111/tid.12255. Epub 2014 Jul 1.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2019-R-03
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Kidney Transplant Infection
-
Clinical Hospital MerkurClinical Hospital Centre ZagrebUnknownKidney Transplant Infection | Kidney Transplant RejectionCroatia
-
Singapore General HospitalRecruitingKidney Transplant Infection | Kidney Transplant Rejection | Kidney Transplant; ComplicationsSingapore
-
Hospital de Clinicas de Porto AlegreActive, not recruitingKidney Transplant Infection | Kidney Transplant Rejection | Kidney Transplant Failure | Kidney Transplant Failure and RejectionBrazil
-
Tongji HospitalAnapure BioScience; Caibo MedTech; SKM BioTechRecruitingKidney Transplant Infection | Kidney Transplant Rejection | Immunosuppression | VirusChina
-
Radboud University Medical CenterUniversity of Wisconsin, MadisonRecruitingKidney Transplant Infection | Kidney Transplant; Complications | Kidney Transplant Failure and RejectionNetherlands
-
Vanderbilt University Medical CenterViraCor LaboratoriesActive, not recruitingLiver Transplant Infection | Kidney Transplant Infection | CMV | Heart Transplant InfectionUnited States
-
University Hospital, GrenobleNot yet recruitingCardiovascular Diseases | Kidney Transplant Infection | Immunosuppression | Kidney Transplant; Complications
-
Institute for Clinical and Experimental MedicineNot yet recruitingKidney Transplant InfectionCzechia
-
Maimónides Biomedical Research Institute of CórdobaCompleted
-
University Hospital, BordeauxCompletedKidney Transplant InfectionFrance
Clinical Trials on Urinary culture and treatment if asymptomatic bacteriuria is detected
-
Cliniques universitaires Saint-Luc- Université...CompletedCardiac Surgical ProceduresBelgium
-
Memorial Sloan Kettering Cancer CenterCompletedEsophageal CancerUnited States
-
Fondation Ophtalmologique Adolphe de RothschildTerminated
-
Institut PasteurInstitut Pasteur de BanguiCompletedHIV Infection | Malaria in PregnancyCentral African Republic
-
Memorial Sloan Kettering Cancer CenterNational Cancer Institute (NCI)CompletedNeuroblastomaUnited States
-
Taizhou HospitalFirst Affiliated Hospital of Zhejiang University; Taizhou First People's Hospital and other collaboratorsUnknown
-
Massachusetts Eye and Ear InfirmaryRecruiting
-
Memorial Sloan Kettering Cancer CenterPfizer; Dana-Farber Cancer Institute; University of Pittsburgh; University of VirginiaCompletedNeurofibromatosis | Meningioma | CNS Cancer | Hemangioblastoma | Intracranial HemangiopericytomaUnited States
-
Martin HuelsmannRecruitingHeart Diseases | Diabetes Mellitus, Type 2New Zealand, Austria, Netherlands, Spain, United Kingdom
-
Memorial Sloan Kettering Cancer CenterTufts Medical Center; Lahey ClinicCompleted