Pivmecillinam With Amoxicillin/Clavulanic Acid for Step Down Oral Therapy in ESBL UTIs
PACUTI
1 other identifier
interventional
330
1 country
5
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 febrile UTI caused by extended spectrum beta-lactamase (ESBL) producing Enterobacterales (EPE).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started May 2023
Typical duration for phase_3
5 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 14, 2021
CompletedFirst Posted
Study publicly available on registry
February 4, 2022
CompletedStudy Start
First participant enrolled
May 29, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 1, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
September 1, 2027
August 28, 2023
August 1, 2023
4.3 years
December 14, 2021
August 25, 2023
Conditions
Outcome Measures
Primary Outcomes (1)
Clinical cure
Clinical cure defined as being alive with absence of fever (≥ 38.3 C) and resolution of, or return to non-infected baseline of, urinary tract symptoms (as defined in inclusion criteria) without additional antibiotic treatment (for UTI symptoms) based on fever control and a semi-structured interview at a live return visit to an independent physician (i.e. not previously involved in the care of the study participant) at an infectious disease clinic.
Clinical cure 10 days (+/- 2 days)
Secondary Outcomes (8)
To compare the recurrence prevalence of EPE (phenotypically same species) in urine cultures 10 +/- 2 days after antibiotic treatment between groups (i.e., microbiological cure).
Up to 28 days
To compare the prevalence of EPE or carbapenemase-producing bacteria in faecal cultures 10 +/- 2 days after antibiotic treatment between groups.
Up to 28 days
To compare participants' perception of treatment tolerability
10 days
To compare the incidence of early study drug discontinuation between groups.
10 days
To compare the incidence of additional antibiotic subscriptions (for UTI) within 28 days between groups.
28 days
- +3 more secondary outcomes
Study Arms (2)
PAC treatment
EXPERIMENTALStandard treatment
ACTIVE COMPARATORInterventions
1 tablet pivmecillinam 400 mg and 1 tablet Amoxicillin/clavulanic acid 875/125 mg, three times daily.
Ciprofloxacin 500 mg twice daily, trimethoprim/sulfamethoxazole 800 mg/160 mg twice daily or ertapenem 1 g once daily.
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Lund Universitylead
Study Sites (5)
Helsingborg hospital
Helsingborg, Sweden
Kristianstad hospital
Kristianstad, Sweden
Skåne University Hospital, Lund
Lund, Sweden
Skåne University Hospital, Malmö
Malmo, Sweden
Västmanland hospital Västerås
Västerås, Sweden
Related Publications (2)
Saad S, Mina N, Lee C, Afra K. Oral beta-lactam step down in bacteremic E. coli urinary tract infections. BMC Infect Dis. 2020 Oct 21;20(1):785. doi: 10.1186/s12879-020-05498-2.
PMID: 33087051BACKGROUNDTverring J, Mansson E, Andrews V, Ljungquist O. Pivmecillinam with Amoxicillin/Clavulanic acid as step down oral therapy in febrile Urinary Tract Infections caused by ESBL-producing Enterobacterales (PACUTI). Trials. 2023 Sep 2;24(1):568. doi: 10.1186/s13063-023-07542-3.
PMID: 37660037DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Oskar Ljungquist, MD, PhD.
Lunds universitet
- STUDY CHAIR
Emeli Månsson, MD, PhD.
Västmanland Hospital Västeras
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- SINGLE
- Who Masked
- OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 14, 2021
First Posted
February 4, 2022
Study Start
May 29, 2023
Primary Completion (Estimated)
September 1, 2027
Study Completion (Estimated)
September 1, 2027
Last Updated
August 28, 2023
Record last verified: 2023-08