Disturbance of the Intestinal Microbiota by Temocillin vs Cefotaxime in Treatment of Febrile Urinary Tract Infections

Urinary Tract Infections Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02959957
• Other study ID #: FoHM/UVI 2015
• Secondary ID: 2015-003898-15
• Status: Completed
• Phase: Phase 4
• Start date: May 20, 2016
• Est. completion date: August 2019

Study information

• Verified date: September 2019
• Source: Public Health Agency of Sweden
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 157
• Est. completion date: August 2019
• Est. primary completion date: August 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Communicable Diseases
• Infection
• Urinary Tract Infections

Intervention

Drug:
• Temocillin
Total antibiotic treatment 7-10 days, of which at least 72 hours (9 doses) initial temocillin administration. In case of bacteraemia at baseline the total antibiotic treatment can be extended up to 14 days.
• Cefotaxime
Total antibiotic treatment 7-10 days, of which at least 72 hours (9 doses) initial cefotaxime administration. In case of bacteraemia at baseline the total antibiotic treatment can be extended up to 14 days.

Locations

Country	Name	City	State
Sweden	Helsingborg Hospital	Helsingborg
Sweden	Centralsjukhuset Kristianstad	Kristianstad
Sweden	Linköping University Hospital	Linköping
Sweden	Skåne University Hospital	Lund
Sweden	Vrinnevisjukhuset i Norrköping	Norrköping
Sweden	Örebro University Hospital	Örebro
Sweden	Östersund Hospital	Östersund
Sweden	Karolinska University Hospital	Solna	Stockholm
Sweden	Capio S:t Görans hospital	Stockholm
Sweden	Sundsvall Hospital	Sundsvall
Sweden	University Hospital of Umeå	Umeå
Sweden	Västmanlands sjukhus i Västerås	Västerås

Sponsors (1)

Lead Sponsor	Collaborator
Håkan Hanberger

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Frequency of adverse events		From the first dose of study drug until 4-6 weeks after discontinuation of antibiotic treatment (parenteral and per oral).
Primary	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.	Superiority analysis.	Within 12 hours after the last dose of study drug.
Secondary	Number of patients with clinical cure in each treatment group.	Clinical cure defined as patient totally recovered with no remaining symptoms of UTI or no recurrence with symptoms or no need of further treatment against the current infection. Non-inferiority analysis.	7-10 days after discontinuation of antibiotic treatment (parenteral and oral).
Secondary	Number of patients with early clinical response.	Non-inferiority analysis.	Within 12 hours after the 9th dose of study drug.
Secondary	Bacteriological cure per patient and per pathogen measured as negative urine Culture <1000 CFU/ml.	Non-inferiority analysis.	7-10 days after discontinuation of antibiotic treatment (parenteral and oral).
Secondary	Early bacteriological response measured as negative urine Culture <1000 CFU/ml.	Non-inferiority analysis.	Within 12 hours after the 9th dose of study drug.
Secondary	Rate of patients with diarrhea (= 3 loose stools per day)		From the first dose of study drug until 7-10 days after discontinuation of antibiotic treatment (parenteral and oral).