Safety and Efficacy of a Weekly Oral Cyclic Antibiotic Programme in the Prevention of Urinary Tract Infection on Neurological Bladder (PACHIU)

A Randomized, Multicenter, Parallel Group Study to Evaluate Safety and Efficacy of a Weekly Oral Cyclic Antibiotic Programme in the Prevention of Urinary Tract Infection on Neurological Bladder

Symptomatic urinary tract infections (UTIs) are one of the main causes of morbidity and the main cause of re-hospitalization in subjects with neurogenic bladder. Long-term antibiotic therapy increases the risk of multi-resistant bacterial infections, without reducing the rate of symptomatic UTIs. Our non-comparative preliminary study has shown that Weekly Oral Cyclic Antibiotic Programme (single, weekly dose of antibiotic X on even weeks, and antibiotic Y on odd weeks) seem to drastically reduce both the number of symptomatic UTIs and the number of hospitalizations in patients with neurogenic bladder, without affecting bacterial ecology.

The objective of this study is to validate this preliminary work with a large-scale randomized, parallel-group, multicenter study.

Study Overview

• Status: Completed
• Conditions: Urinary Tract Infection; Neurogenic Bladder
• Intervention / Treatment: Drug: Weekly Oral Cyclic Antibiotic programme

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Phase 4

Contacts and Locations

Study Locations

• France
  • Garches, France, 92380
    • University Hospital, Raymond Poincaré / APHP
  • Nantes, France, 44000
    • University Hospital, St Jacques / NANTES
  • Rennes, France, 35000
    • University Hospital, Pontchaillou / RENNES
  • Tours, France, 37000
    • University Hospital, Bretonneau / TOURS

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• subject over 18 years of age
• having a neurogenic bladder with automatic catheter and pharmacologic disconnection of the detrusor muscle
• having at least 4 symptomatic UTIs per year with bacterial sensitivity to the chosen antibiotics
• having given full consent to participate in the study
• being the recipient of social security benefits

Exclusion Criteria:

• known allergy or hypersensitivity to useful antibiotics (to which the bacterium or bacteria are sensitive) or to one of their components
• other contraindication in the administering of useful antibiotics
• urinary volume flow >500 ml during automatic catheter
• different urinary drainage method than automatic catheter
• occurrence of stones in the urinary tract
• infection due to endo urinary material (urinary prosthesis, ureteral stent)
• creatinine clearance <60 ml/min
• patient under guardianship
• women who are pregnant, nursing, or who may become pregnant

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Weekly Oral Cyclic Antibiotic programme	Drug: Weekly Oral Cyclic Antibiotic programme; The Weekly Oral Cyclic Antibiotic Programme consisted of the alternate administration of an antibiotic once per week. The antibiotics that were chosen (efficient for urinary tract infection, well tolerated, low selection pressure) included : Amoxicillin 6000 mg, Amoxicillin/clavulanic acid 3000 mg, Cefixime 400 mg, Fosfomycin trometamol 6000 mg, Trimethoprim/sulfamethoxazole 2400 mg. During week A,the patient received a single antibiotic (A), and the following week B the patient was given another antibiotic (B). For each patient, antibiotics were specifically chosen according to the results of urine cultures.
No Intervention: Classic care

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of symptomatic UTIs	Symptomatic UTIs are defined by the presence of infection or reinfection by the same bacteria, in combination with the presence of definite clinical signs of infection (autonomous hyper-reflexivity, spasticity, leakage, contractures, pyuria, fever, shivers).	During the 6-month follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The number of feverish UTIs	The number of feverish UTIs	During the 6-month follow-up
The number of hospitalizations	The number of hospitalizations	During the 6-month follow-up.
The duration of UTI-related hospitalizations	The duration of UTI-related hospitalizations	During the 6-month follow-up
The tolerance level to the Weekly Oral Cyclic Antibiotic Programme, measured by any adverse effects to antibiotics	The tolerance level to the Weekly Oral Cyclic Antibiotic Programme, measured by any adverse effects to antibiotics	During the 6-month follow-up.
The global antibiotic consumption.	The global antibiotic consumption.	During the 6-month follow-up
The number of urine culture negative	The number of urine culture negative	During the 6-month follow-up
The emergence of multi-resistant bacteria in urine (cultures), digestive bacteria (anal swabs), oro-pharynx bacteria (nasal swabs), and semi-quantitative research of multi-resistant bacteria in the stool.	The emergence of multi-resistant bacteria in urine (cultures), digestive bacteria (anal swabs), oro-pharynx bacteria (nasal swabs), and semi-quantitative research of multi-resistant bacteria in the stool.	During the 6-month follow-up
the quality of life	A scale to measure the quality of life.	During the 6-month follow-up

Collaborators and Investigators

• Sponsor: University Hospital, Tours
• Investigators: Principal Investigator: Louis BERNARD, MD-PhD, University Hospital, Tours

Publications and helpful links

General Publications

• Dinh A, Hallouin-Bernard MC, Davido B, Lemaignen A, Bouchand F, Duran C, Even A, Denys P, Perrouin-Verbe B, Sotto A, Lavigne JP, Bruyere F, Grall N, Tavernier E, Bernard L. Weekly Sequential Antibioprophylaxis for Recurrent Urinary Tract Infections Among Patients With Neurogenic Bladder: A Randomized Controlled Trial. Clin Infect Dis. 2020 Dec 15;71(12):3128-3135. doi: 10.1093/cid/ciz1207.

Study record dates

Study Major Dates

• Study Start: August 1, 2011
• Primary Completion (Actual): January 1, 2016
• Study Completion (Actual): February 1, 2017

Study Registration Dates

• First Submitted: June 23, 2011
• First Submitted That Met QC Criteria: July 1, 2011
• First Posted (Estimate): July 6, 2011

Study Record Updates

• Last Update Posted (Actual): February 24, 2017
• Last Update Submitted That Met QC Criteria: February 23, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: urinary tract infection; neurogenic bladder
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Urologic Diseases; Urinary Bladder Diseases; Neurologic Manifestations; Disease Attributes; Infections; Communicable Diseases; Urinary Tract Infections; Urinary Bladder, Neurogenic; Anti-Infective Agents; Anti-Bacterial Agents
• Other Study ID Numbers: PHRI06-LB/PACHIU; 2010-021241-44 (EudraCT Number); A101183-72 (Other Identifier: Afssaps); 2010-R31 (Other Identifier: CPP)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No