Clinical trial NCT02959957: Disturbance of the Intestinal Microbiota by Temocillin vs Cefotaxime in Treatment of Febrile Urinary Tract Infections
Official title: A Randomized, Controlled, Multicentre Trial of Collateral Damage on the Intestinal Microbiota Inferred by Temocillin Versus Cefotaxime in Patients Receiving Empirical Treatment for Febrile Urinary Tract Infections
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Urinary Tract Infections
Lead sponsor: Public Health Agency of Sweden
Sponsor class: OTHER_GOV
First posted: 2016-11-09
Enrollment: 157
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will evaluate the ecological impact on the intestinal microbiota and compare the safety and efficacy of temocillin compared to cefotaxime, in empiric treatment of febrile UTI. Half of participants will receive temocillin and the other half will receive cefotaxime.

Detailed description: Temocillin is a narrow spectrum antibiotic with activity against gram negative bacteria inclusive many ESBL producing bacteria. Temocillin is approved and marketed in a few European countries since the 1980´s but not in Sweden.

The aim of the study is to find an ecological favorable alternative to cephalosporins in the treatment of this common indication.

The hypothesis is that treatment with temocillin causes less disturbances on the intestinal microbiota while at least comparable efficacy.

The study will be performed as an open prospective multicentre study with two parallel groups comparing 2 g temocillin three times daily with 1-2 g cefotaxim three times daily for 7-10 days in male and female adult patients with febrile urinary tract infection.

Eligibility criteria: Inclusion Criteria:

* Males and females ≥ 18 years of age with suspected or confirmed febrile UTI, fulfilling at least one of the following signs and symptoms:

  * Flank pain or suprapubic pain, Tenderness over the kidney on physical examination, Urinary symptoms such as dysuria, urinary frequency or urinary urgency
* Fever ≥ 38.0°C (highest temperature recorded at home or at the hospital)
* Positive urinalysis tests (U-Nitrit and/or U-LPK)
* Have a pre-treatment baseline urinary culture obtained
* Require iv antibacterial treatment of the presumed infection
* Fertile women: Agree to practice highly effective anti-contraceptive methods from study-start to TOC
* Signed informed consent

Exclusion Criteria:

* Have a documented history of hypersensitivity or allergic reaction to any beta-lactam
* Pregnant or nursing women
* Receipt of any prior potentially therapeutic antibacterial agent within 1 month before randomisation and sampling for urine and faecal cultures. Exceptions will prior treatment with pivmecillinam or nitrofurantoin.
* Known chronic renal insufficiency (creatinine clearance \< 10 mL/min at screening as estimated by Cockcroft-Gault), or receiving intermittent haemodialysis or peritoneal dialysis
* Known colonization with ESBL
* Any condition or circumstance that, in the opinion of the investigator, would compromise the safety of the subject or the quality of study data.

Primary outcomes:
measure: Number of patients with emergence of any of the two following events: Colonisation or infection with C. difficile and/or with Enterobacteriaceae resistant to 3rd generation cephalosporins. Measured in cultures from faecal samples.
timeFrame: Within 12 hours after the last dose of study drug.
Secondary outcomes:
measure: Number of patients with clinical cure in each treatment group.
timeFrame: 7-10 days after discontinuation of antibiotic treatment (parenteral and oral).
measure: Number of patients with early clinical response.
timeFrame: Within 12 hours after the 9th dose of study drug.
measure: Bacteriological cure per patient and per pathogen measured as negative urine Culture <1000 CFU/ml.
timeFrame: 7-10 days after discontinuation of antibiotic treatment (parenteral and oral).
measure: Early bacteriological response measured as negative urine Culture <1000 CFU/ml.
timeFrame: Within 12 hours after the 9th dose of study drug.
measure: Rate of patients with diarrhea (≥ 3 loose stools per day)
timeFrame: From the first dose of study drug until 7-10 days after discontinuation of antibiotic treatment (parenteral and oral).
Other outcomes:
measure: Frequency of adverse events
timeFrame: From the first dose of study drug until 4-6 weeks after discontinuation of antibiotic treatment (parenteral and per oral).
Locations:
city: Solna
country: Sweden
facility: Karolinska University Hospital
state: Stockholm
city: Helsingborg
country: Sweden
facility: Helsingborg Hospital
city: Kristianstad
country: Sweden
facility: Centralsjukhuset Kristianstad
city: Linköping
country: Sweden
facility: Linköping University Hospital
city: Lund
country: Sweden
facility: Skåne University Hospital
city: Norrköping
country: Sweden
facility: Vrinnevisjukhuset i Norrköping
city: Stockholm
country: Sweden
facility: Capio S:t Görans hospital
city: Sundsvall
country: Sweden
facility: Sundsvall Hospital
city: Umeå
country: Sweden
facility: University Hospital of Umeå
city: Västerås
country: Sweden
facility: Västmanlands sjukhus i Västerås
city: Örebro
country: Sweden
facility: Örebro University Hospital
city: Östersund
country: Sweden
facility: Östersund Hospital
Study officials:
affiliation: University Hospital, Linkoeping
name: Håkan Hanberger, Professor
role: PRINCIPAL_INVESTIGATOR
References: