Status:
RECRUITING
Pivmecillinam With Amoxicillin/Clavulanic Acid for Step Down Oral Therapy in ESBL UTIs
Lead Sponsor:
Lund University
Conditions:
Urinary Tract Infections
Bacteremia
Eligibility:
All Genders
18-130 years
Phase:
PHASE3
Brief Summary
To evaluate if the combination of pivmecillinam and clavulanic acid (PAC) is non-inferior to ciprofloxacin, trimethoprim-sulfamethoxazole or ertapenem as step down oral therapy in patients with febril...
Detailed Description
A recent observational cohort study supports the notion that beta-lactams can be used with similar efficacy to fluoroquinolones as step down therapy in bacteremic E. coli UTI's. As such, pivmecillinam...
Eligibility Criteria
Inclusion
- Inclusion Criteria:
- Age ≥ 18 years
- Fever (≥ 38.3 C) or shaking chills at least once at home or in hospital
- Clinical suspicion of UTI including at least one of the following symptoms:
- Dysuria, urinary urgency, difficulty urinating, new or worsened urinary incontinence, macroscopic haematuria or increased urinary frequency
- Low abdominal pain or flank pain with percussion or palpation tenderness over kidneys and/or bladder.
- Urine (≥ 103 CFU/mL) and/or blood culture positive for EPE\* with susceptibility to pivmecillinam†.
- In-patient who has received 1-5 days of EPE-active‡ intravenous antibiotics
- Discontinuing parenteral treatment and starting treatment with oral antibiotics is considered safe according to the treating physician.
- EPE refers to ESBL-producing Enterobacterales. This includes Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Klebsiella oxytoca, and Citrobacter koseri.
- Susceptibility for pivmecillinam in the study is based on zone diameter breakpoints for pyelonephritis (≥ 20 mm) which was received by personal communication with professor Christian Giske, the chairman of the European Committee of Antimicrobial Susceptibility Testing (EUCAST) (26).
- EPE-active intravenous antibiotics refers to EUCAST susceptibility testing and will most often be piperacillin-tazobactam, meropenem or imipenem-cilastatin in the Swedish setting, and less often aminoglycosides or newer beta-lactamase-inhibitor-containing beta-lactam antibiotics (27). Participants who have only received one dose of EPE-active intravenous antibiotics are also eligible and are considered within the "1-5 days" of antibiotics.
- Patients may only be recruited and randomised once in this trial.
- Exclusion criteria (any of the following)
- Known or suspected pregnancy.
- Known or suspected life-threatening allergy towards beta-lactam antibiotics.
- Clinical isolate of EPE is resistant to ciprofloxacin, TMX and ertapenem.
- Severe renal insufficiency with estimated glomerular filtration rate (eGFR) \<10mL/min or requiring any form of dialysis.
- Severe decompensated liver failure (i.e., child Pugh class B or C).
- Genetic metabolic diseases associated with severe carnitine deficiency.
- Megaloblastic haematopoiesis.
- Co-treatment with valproate or valproic acid (due to interaction with pivmecillinam and ertapenem respectively)
- Other reason to which patient is unfit to be included in the study according to treating physician, e.g., cognitive impairment preventing informed consent and follow-up, inability to speak and/or read Swedish, missing national personal identification number or missing telephone number preventing follow-up or planned duration of antibiotics \> 10 days due to complicating factors.
Exclusion
Key Trial Info
Start Date :
May 29 2023
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
September 1 2027
Estimated Enrollment :
330 Patients enrolled
Trial Details
Trial ID
NCT05224401
Start Date
May 29 2023
End Date
September 1 2027
Last Update
August 28 2023
Active Locations (5)
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1
Helsingborg hospital
Helsingborg, Sweden
2
Kristianstad hospital
Kristianstad, Sweden
3
Skåne University Hospital, Lund
Lund, Sweden
4
Skåne University Hospital, Malmö
Malmo, Sweden