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Clinical Trials in Sweden / NCT05224401
Recruiting Phase 3

Pivmecillinam With Amoxicillin/Clavulanic Acid for Step Down Oral Therapy in ESBL UTIs

NCT05224401 · tracked via the Priya Life Science Sweden tracker
Phase
Phase 3
Started
2023-05-29
Last updated
2023-08-28

Condition(s) studied

Urinary Tract InfectionsBacteremiaAntibiotic Resistant Infection

Investigational drug(s) / intervention(s)

Pivmecillinam and amoxicillin/clavulanic acidStandard treatment, ciprofloxacin, trimethoprim/sulfamethoxazole or ertapenem depending on susceptibility

Pivmecillinam and amoxicillin/clavulanic acid: 1 tablet pivmecillinam 400 mg and 1 tablet Amoxicillin/clavulanic acid 875/125 mg, three times daily.

Standard treatment, ciprofloxacin, trimethoprim/sulfamethoxazole or ertapenem depending on susceptibility: Ciprofloxacin 500 mg twice daily, trimethoprim/sulfamethoxazole 800 mg/160 mg twice daily or ertapenem 1 g once daily.

Study 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 febrile UTI caused by extended spectrum beta-lactamase (ESBL) producing Enterobacterales (EPE).

Eligibility

Sex
ALL
Min age
18 Years
Max age
130 Years
Healthy volunteers
No
Inclusion Criteria: 1. Age ≥ 18 years 2. Fever (≥ 38.3 C) or shaking chills at least once at home or in hospital 3. Clinical suspicion of UTI including at least one of the following symptoms: 1. Dysuria, urinary urgency, difficulty urinating, new or worsened urinary incontinence, macroscopic haematuria or increased urinary frequency 2. Low abdominal pain or flank pain with percussion or palpation tenderness over kidneys and/or bladder. 4. Urine (≥ 103 CFU/mL) and/or blood culture positive for EPE\* with susceptibility to pivmecillinam†. 5. In-patient who has received 1-5 days of EPE-active‡ intravenous antibiotics 6. 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) 1. Known or suspected pregnancy. 2. Known or suspected life-threatening allergy towards beta-lactam antibiotics. 3. Clinical isolate of EPE is resistant to ciprofloxacin, TMX and ertapenem. 4. Severe renal insufficiency with estimated glomerular filtration rate (eGFR) \<10mL/min or requiring any form of dialysis. 5. Severe decompensated liver failure (i.e., child Pugh class B or C). 6. Genetic metabolic diseases associated with severe carnitine deficiency. 7. Megaloblastic haematopoiesis. 8. Co-treatment with valproate or valproic acid (due to interaction with pivmecillinam and ertapenem respectively) 9. 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.

Primary outcome measure(s)

Trial sites (5)

FacilityCityRegionStatus
Helsingborg hospital Helsingborg Sweden Recruiting
Kristianstad hospital Kristianstad Sweden Recruiting
Skåne University Hospital, Lund Lund Sweden Recruiting
Skåne University Hospital, Malmö Malmö Sweden Recruiting
Västmanland hospital Västerås Västerås Sweden Recruiting

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Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT05224401 on ClinicalTrials.gov ↗ ← All trials in Sweden