PROSTASHORT: Antibiotic Treatment for 7 Days Versus 14 Days in Patients With Acute Male Urinary Tract Infection

Sponsor

Assistance Publique - Hôpitaux de Paris (Other)

Overall Status

Unknown status

CT.gov ID

NCT02424461

Collaborator

(none)

400

Enrollment

Location

Arms

Duration (Months)

5.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study will investigate the treatment of urinary tract infection (UTI) in men. The investigators are looking to see if shorter duration of antibiotics (7 days) is not inferior to a longer duration of antibiotics (14 days). The investigators will also study whether longer treatment leads to an increase in antibiotic resistant bacteria in the gut microbiota or an increase in drug side effects.

Condition or Disease	Intervention/Treatment	Phase
Acute Male Urinary Tract Infection	Drug: Ceftriaxone Drug: Ofloxacine Drug: Ofloxacine Drug: Placebo of ofloxacine	Phase 3

Detailed Description

The proposed study is a multicentre, non-inferiority, double blind, randomized placebo-controlled trial of treatment duration for male urinary tract infection (UTI) due to fluoroquinolones susceptible bacteria. Specifically, 284 men with a UTI will be randomized to 7 vs. 14 days of antimicrobial treatment. The primary outcome is resolution of fever, sterile urine analysis 4 weeks after completion of antimicrobial therapy and no antibiotic therapy active against the bacterial strain responsible for the UTI within the 4 week period following antimicrobial therapy. Secondary outcomes include the intestinal carriage of antimicrobial-resistant Gram-negative bacilli at the end of treatment, the incidence and severity of adverse drug events and the recurrent UTI within the treatment period and 4 weeks and 12 weeks of completing active study medication.

Currently, the optimal treatment duration for male UTI is unknown. Only one randomized study showed no difference in outcomes, in patients treated with ciprofloxacin during 14 vs. 28 days. However, this study was underpowered and included patient in a single center. Current treatment guidelines are not consensual and recommend treating men with UTI for 7 to 4 or 6 weeks. Shorter durations may expose patients to recurrence when longer duration may be associated with increase in Clostridium difficile infection and antimicrobial resistance. Longer-duration treatment is also more costly and inconvenient to patients. Thus, since longer-duration treatment is associated with some adverse outcomes, in order to justify longer-duration treatment thee must be some clinically significant benefit to the extended treatment.

The proposed randomized placebo-controlled trial will test the hypothesis that 7 days of antimicrobial treatment is non-inferior for the resolution of fever and microbiological success when compared to 14 days of treatment.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

400 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Antibiotic Treatment for 7 Days Versus 14 Days in Patients With Acute Male Urinary Tract Infection Due to Fluoroquinolones Susceptible Bacteria: a Multicentre, Non-inferiority, Double Blind, Randomized Placebo-controlled Trial

Study Start Date :

Feb 1, 2015

Actual Primary Completion Date :

Feb 1, 2020

Anticipated Study Completion Date :

Dec 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 7 day-antimicrobial treatment Ceftriaxone : 1 injection 1 g per day for 2 days Ofloxacine : 400 mg/jour (200 mg/ jour in case of renal failure) for seven days Placebo of ofloxacine for 7 days	Drug: Ceftriaxone 1 injection 1 g per day for 2 days Drug: Ofloxacine 400 mg/jour (200 mg/ jour in case of renal failure) for seven days Drug: Ofloxacine 400 mg/jour (200 mg/ jour in case of renal failure) for 14 days
Active Comparator: 14-day antimicrobial treatment Ceftriaxone : 1 injection 1 g per day for 2 days Ofloxacine : 400 mg/jour (200 mg/ jour in case of renal failure) for 14 days	Drug: Ceftriaxone 1 injection 1 g per day for 2 days Drug: Ofloxacine 400 mg/jour (200 mg/ jour in case of renal failure) for seven days Drug: Placebo of ofloxacine Placebo of ofloxacine for 7 days

Arm

Intervention/Treatment

Active Comparator: 7 day-antimicrobial treatment

Ceftriaxone : 1 injection 1 g per day for 2 days Ofloxacine : 400 mg/jour (200 mg/ jour in case of renal failure) for seven days Placebo of ofloxacine for 7 days

Drug: Ceftriaxone

1 injection 1 g per day for 2 days

Drug: Ofloxacine

400 mg/jour (200 mg/ jour in case of renal failure) for seven days

Drug: Ofloxacine

400 mg/jour (200 mg/ jour in case of renal failure) for 14 days

Active Comparator: 14-day antimicrobial treatment

Ceftriaxone : 1 injection 1 g per day for 2 days Ofloxacine : 400 mg/jour (200 mg/ jour in case of renal failure) for 14 days

Drug: Ceftriaxone

1 injection 1 g per day for 2 days

Drug: Ofloxacine

400 mg/jour (200 mg/ jour in case of renal failure) for seven days

Drug: Placebo of ofloxacine

Placebo of ofloxacine for 7 days

Outcome Measures

Primary Outcome Measures

Success defined by resolution of fever [day 42]
Defined by 3 criteria that should be fulfilled: resolution of fever between the end of treatment and 4 weeks thereafter (except fever not related to urine infection), sterile urine (except alpha-hemolytic streptococus, Lactobacillus, Corynebacterium, Gardnerella or coagulase negative Staphylococcus) analysis 4 weeks after completion of antimicrobial therapy, and no antibiotic therapy active against the bacterial strain responsible for the UTI within the 4 week period following antimicrobial therapy

Secondary Outcome Measures

Intestinal carriage of antimicrobial-resistant Gram-negative bacilli [4 and 12 weeks]
intestinal carriage of antimicrobial-resistant Gram-negative bacilli at the end of treatment and 4 and 12 weeks after completing study medication, as compared to a baseline sample taken before treatment
Incidence and severity of adverse drug events [4 and 12 weeks]
the incidence and severity of adverse drug events within the treatment period and in the 4 and 12 weeks after completing study medication
Recurrent UTI [4 and 12 weeks]
Recurrent UTI within 4 weeks and 12 weeks of completing active study medication

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Inclusion Criteria:

Male gender, 18 years and older
New-onset of the following criteria:

Temperature ≥38° Celsius or <36° Celsius (or at least once in the 3 previous days), AND
at least one of following symptoms/findings: dysuria, urinary frequency, urgency, urinary burning, hematuria, perineal pain, supra-pubic pain or urinary retention, painful prostate (digital prostate examination)

Leucocyturia ≥ 10/ mm3
Urinary signs/symptoms within the 3 previous months
Urinary culture yielding a single pathogen, at least10^3 colony-forming unit (CFU)/ml, susceptible to nalidixic acid, ofloxacine and ceftriaxone.
Oral route for study drug
Normal Ultrasound prostatic findings (no abscess and post-void residual urine volume < 100 ml).

Exclusion Criteria:

Septic shock
Admission to the hospital (for > 48 h) at the time of diagnosis
Treatment for UTI in the past year
Urinary catheter
Severe disease with strong probability of death within 3 months
Severe allergy or contraindication to fluoroquinolones or beta-lactams
Not able to give informed consent
Antimicrobial therapy with fluoroquinolone or aminoglycoside in the 3 previous days
Neutropenia (neutrophils count < 500/mm3)
Renal insufficiency (creatinin clearance ≤ 20 ml/min)
Glucose - 6 - Phosphate - Dehydrogenase deficiency
Significant cognitive disorders
Uncontrolled epilepsy
History of tendinitis
Elevated liver enzyme levels (aspartate aminotransferase (ASAT), Alanine Amino Transferase (ALAT) ≥ 5 upper limit of normal range (ULN))
Myasthenia
Significant psychiatric disorders
Galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption.
Patient under guardianship patient, guardianship or without social security cover