Urinary Tract InfectionsPhase 3PACUTINCT05224401
Pivmecillinam With Amoxicillin/Clavulanic Acid for Step Down Oral Therapy in ESBL UTIs
A Phase 3 study testing Pivmecillinam and amoxicillin/clavulanic acid and Standard treatment, ciprofloxacin, trimethoprim/sulfamethoxazole or ertapenem depending on susceptibility in people with Urinary Tract Infections and Bacteremia, run by Lund University at 5 sites in Sweden.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 130 years
- Conditions the study is for
- Urinary Tract Infections, Bacteremia, Antibiotic Resistant Infection
- What is being tested?
- Pivmecillinam and amoxicillin/clavulanic acid and Standard treatment, ciprofloxacin, trimethoprim/sulfamethoxazole or ertapenem depending on susceptibility
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 330 participants
- Where
- 5 sitesSweden
- Study dates
- 29 May 2023to 1 Sep 2027
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 130 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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†.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
5 sites in 1 country. Contact the study team or a site near you to ask about taking part.
5 sites in 1 country
Sweden5 sites, 5 recruiting
- Recruiting
Helsingborg hospital
Helsingborg
Oskar Ljungquist, PhD
- Recruiting
Kristianstad hospital
Kristianstad
Emil Thiman
- Recruiting
Skåne University Hospital, Lund
Lund
Christian Kampmann, PhD
- Recruiting
Skåne University Hospital, Malmö
Malmö
Johan Tham, Ass professor
- Recruiting
Västmanland hospital Västerås
Västerås
Emeli Månsson, PhD
About this study
Official title: Pivmecillinam With Amoxicillin/Clavulanic Acid for Step Down Oral Therapy in Febrile UTIs Caused by ESBL-producing Enterobacterales (PACUTI)
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).
Read the 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 clavulanic acid (PAC) constitute an appealing per oral alternative, but the combination's safety and efficacy has not been evaluated in a clinical trial The aim of this trial is to investigate whether the PAC combination is non-inferior to ciprofloxacin, trimethoprim-sulfamethoxazole or ertapenem as step down oral therapy in treating EPE-causing febrile UTI.
- Being tested
- Pivmecillinam and amoxicillin/clavulanic acid, Standard treatment, ciprofloxacin, trimethoprim/sulfamethoxazole or ertapenem depending on susceptibility
- Medical subject headings
- Urinary Tract Infections, Bacteremia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pivmecillinam and amoxicillin/clavulanic acidDrug
Also called Coactin or selexid etc, and Augmentin or Clavulin etc
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 susceptibilityDrug
Also called Bactrim
Ciprofloxacin 500 mg twice daily, trimethoprim/sulfamethoxazole 800 mg/160 mg twice daily or ertapenem 1 g once daily.
| Study group | Role | What they receive |
|---|---|---|
| PAC treatment | Experimental | Not described Receives: Drug: Pivmecillinam and amoxicillin/clavulanic acid |
| Standard treatment | Active comparator | Not described Receives: Drug: Standard treatment, ciprofloxacin, trimethoprim/sulfamethoxazole or ertapenem depending on susceptibility |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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).
Yes or no.
Measured: 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.
Yes or no.
Measured: Up to 28 days
To compare participants' perception of treatment tolerability
Tolerability is measured on a 1-10 scale.
Measured: 10 days
To compare the incidence of early study drug discontinuation between groups.
Yes or no.
Measured: 10 days
To compare the incidence of additional antibiotic subscriptions (for UTI) within 28 days between groups.
Yes or no.
Measured: 28 days
To compare re-admission to hospital (due to UTI-related symptoms) within 28 days between groups.
Yes or no.
Measured: 28 days
To compare the incidence of drug-related serious adverse events (SAE) within 28 days between groups.
Yes or no.
Measured: 28 days
To compare the all-cause mortality within 28 days between groups.
Yes or no.
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Feb 2022
- Study start29 May 2023
- Primary completion1 Sep 2027 (estimated)
- Study completion1 Sep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Urinary Tract InfectionsStudies of the same condition, open and under way.
- More trials run by Lund UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 330 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Lund University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Oskar Ljungquist, MD, PhD., Principal investigator, Lunds universitetEmeli Månsson, MD, PhD., Study chair, Västmanland Hospital Västeras
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05224401
- Sponsor's protocol ID
- 2021-PACUTI
- Acronym
- PACUTI
- Status last verified
- Aug 2023
- First submitted
- 14 Dec 2021
- Last updated
- 28 Aug 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Yes.
Publications
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.
PubMed 33087051Tverring 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.
PubMed 37660037
Study at a glance
From the registry record, last updated by the sponsor on 28 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pivmecillinam With Amoxicillin/Clavulanic Acid for Step Down Oral Therapy in Febrile UTIs Caused by ESBL-producing Enterobacterales (PACUTI)
- ClinicalTrials.gov ID
- NCT05224401
- Acronym / sponsor ID
- PACUTI / 2021-PACUTI
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 330 participants (estimated)
- Lead sponsor
- Lund UniversityUniversity, hospital or other
- Study start
- 29 May 2023 (actual)
- Primary completion
- 1 Sep 2027 (estimated)
- Study completion
- 1 Sep 2027 (estimated)
- First posted
- 4 Feb 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
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 clavulanic acid (PAC) constitute an appealing per oral alternative, but the combination's safety and efficacy has not been evaluated in a clinical trial The aim of this trial is to investigate whether the PAC combination is non-inferior to ciprofloxacin, trimethoprim-sulfamethoxazole or ertapenem as step down oral therapy in treating EPE-causing febrile UTI.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| PAC treatment | Experimental | Drug: Pivmecillinam and amoxicillin/clavulanic acid |
| Standard treatment | Active comparator | Drug: Standard treatment, ciprofloxacin, trimethoprim/sulfamethoxazole or ertapenem depending on susceptibility |
Who may qualify
- Ages
- 18 to 130 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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:
- 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
Key exclusion criteria (9 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pivmecillinam and amoxicillin/clavulanic acidAlso: Coactin or selexid etc, and Augmentin or Clavulin etc1 tablet pivmecillinam 400 mg and 1 tablet Amoxicillin/clavulanic acid 875/125 mg, three times daily. | Drug | PAC treatment |
| Standard treatment, ciprofloxacin, trimethoprim/sulfamethoxazole or ertapenem depending on susceptibilityAlso: BactrimCiprofloxacin 500 mg twice daily, trimethoprim/sulfamethoxazole 800 mg/160 mg twice daily or ertapenem 1 g once daily. | Drug | Standard treatment |
Primary outcome
Clinical cure
Time frame: Clinical cure 10 days (+/- 2 days)
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.
8 secondary outcomes
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).
Time frame: 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.
Time frame: Up to 28 days
To compare participants' perception of treatment tolerability
Time frame: 10 days
To compare the incidence of early study drug discontinuation between groups.
Time frame: 10 days
To compare the incidence of additional antibiotic subscriptions (for UTI) within 28 days between groups.
Time frame: 28 days
To compare re-admission to hospital (due to UTI-related symptoms) within 28 days between groups.
Time frame: 28 days
To compare the incidence of drug-related serious adverse events (SAE) within 28 days between groups.
Time frame: 28 days
To compare the all-cause mortality within 28 days between groups.
Time frame: 28 days
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Aug 2023.
- Background: PubMed 33087051Saad 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.
- Derived from this study: PubMed 37660037Tverring 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.
- Individual participant dataSharing planned: Undecided. Yes.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Oskar Ljungquist, MD, PhD. principal investigator
Lunds universitet
Emeli Månsson, MD, PhD. study chair
Västmanland Hospital Västeras
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Pivmecillinam and amoxicillin/clavulanic acid and Standard treatment, ciprofloxacin, trimethoprim/sulfamethoxazole or ertapenem depending on susceptibility in people with Urinary Tract Infections and Bacteremia, run by Lund University at 5 sites in Sweden.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 28 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Oskar Ljungquist, M.D, PhD (+46424063182, oskar.ljungquist@med.lu.se), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical cure (time frame: Clinical cure 10 days (+/- 2 days)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05224401, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Aug 2023.