Pivmecillinam as Oral Step-Down Treatment for Escherichia Coli Febrile Urinary Tract Infection Versus Standard of Care

NCT07236944 | Recruiting Phase 4

• 2 other identifiers: PIVOT2023-503447-33-00
• Study Type: interventional
• Target: 560
• Locations: 2 countries
• Sites: 13

Brief Summary

The goal of this clinical trial is to learn if oral treatment with pivmecillinam is effective to treat febrile urinary tract infections in adult patients. Hospitalized patients who have received 2-4 days of intravenous antibiotic therapy for febrile urinary tract infections, and have responded to treatment, will be randomized to either pivmecillinam or standard treatment (other oral or intravenous antibiotics). The main question the study aims to answer is if oral follow-up with pivmecillinam is as effective as standard treatment. Patients will be evaluated for clinical response (resolution of fever and urinary tract symptoms) and microbiological response (no growth of bacteria in urine) 7 and 28 days after the end of treatment. Patients will also be asked about side effects. Some of the participants will also be examined for changes in the gut microbiome and drug exposures in blood and urine. Participants will:

1. 1.Keep a patient diary to record antibiotic intake, body temperature, urinary tract symptoms, and suspected side effects until 7 days after end of treatment.
2. 2.Participate in phone interviews 7 and 28 days after end of treatment to assess clinical response.
3. 3.Provide urine samples 7 and 28 days after end of treatment to evaluate microbiological response.
4. 4.A subgroup (60 patients) will provide fecal samples at five time-points over three months to assess antibiotic-induced changes in the gut microbiome.
5. 5.A subgroup (30 patients) treated with to pivmecillinam will provide blood and urine samples to determine the pharmacokinetics of mecillinam during one dosing interval.

Conditions

Febrile Urinary Tract Infection

Keywords

Urinary Tract Infection; Pivmecillinam; Escherichia coli

Outcome Measures

Primary Outcomes (1)

• Clinical response (primary endpoint).

  Clinical response: i) no new healthcare contacts or antibiotic treatments for suspected or proven UTI, ii) sustained defervescence (\< 38°C), and iii) patient-documented resolution of fUTI symptoms that were present and recorded in the eCRF at trial entry (and no new fUTI symptoms) at test of cure (TOC), which will be performed 7 (+/-2) days after end of treatment (EOT). The evaluation of clinical response (primary endpoint) will be performed by blinded assessors.

  7 (+/-2) days after EOT

Secondary Outcomes (4)

• Sustained clinical response

  28 (+/- 2) days after EOT

• Microbiological response

  7 (+/-2) days after EOT

• Sustained microbiological response

  28 (+/- 2) days after EOT

• Occurrence and severity of adverse events

  From start of study treatment until test of cure 7 (+/-2) days after EOT

Study Arms (2)

Standard of care

ACTIVE COMPARATOR

The control group will receive standard of care treatment at the discretion of the responsible physician and according to existing treatment guidelines.

Drug: Standard of Care (Investigator Choice)

Pivmecillinam

EXPERIMENTAL

Pivmecillinam (high dose, 400 mg four times daily).

Drug: Pivmecillinam

Interventions

Standard of Care (Investigator Choice) DRUG

The control group will receive standard of care antibiotic treatment at the discretion of the responsible physician and according to existing treatment guidelines, with a total treatment duration of 7 to 14 days. The following antibiotics will be considered adequate. Intravenous antibiotics: 1) Penicillins; ampicillin, piperacillin/tazobactam, 2) cephalosporins; cefotaxime, cefuroxime, ceftriaxone, 3) carbapenems; ertapenem, imipenem, meropenem, 4) monobactams; aztreonam, 5) aminoglycosides; amikacin, gentamicin, tobramycin, 6) other; fosfomycin. Oral antibiotics: 1) ciprofloxacin, 2) trimethoprim-sulfamethoxazole, 3) amoxicillin or amoxicillin/clavulanic acid provided that the isolated E. coli is determined susceptible according to the EUCAST-breakpoint for systemic infections, i.e., MIC ≤ 8 mg/l, and high dosing is used (≥750 mg amoxicillin x 3 and ≥750 mg amoxicillin/125 mg clavulanic acid x 3, respectively) and 4) tebipenem (if approved by the EMA).

Standard of care

Pivmecillinam DRUG

Patients randomized to pivmecillinam will be provided with 400 mg tablets for 3 to 8 days of treatment, to be taken four times daily, resulting in a total treatment duration of 7 or 10 days (including the initial 2-4 days of intravenous treatment). The shorter treatment duration of 7 days will be used for female patients with no complicating factors (structural or functional urologic abnormalities, urinary tract catheterization, and diabetes mellitus). The longer treatment duration of 10 days will be used for all other patients.

Pivmecillinam

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥18 years of age.
• Diagnosis of fUTI, defined as i) fever ≥ 38°C and ii) at least one of the following: flank pain or pelvic pain, nausea or vomiting, dysuria, urinary frequency or urgency, and costovertebral angle tenderness on physical examination.
• Growth of E. coli in urine with antimicrobial susceptibility to mecillinam.
• Adequate intravenous antibiotic treatment for fUTI (defined below) for 2 days to which the isolated E. coli is determined susceptible.
• Defervescence and hemodynamic stability for at least 24 hours, according to the responsible physician.
• Planned treatment with one of the following antibiotics, should the patient be randomized to the standard-of-care arm. Intravenous antibiotics: 1) Penicillins; ampicillin, piperacillin/tazobactam, ≥2) cephalosporins; cefotaxime, cefuroxime, ceftriaxone, 3) carbapenems; ertapenem, imipenem, meropenem, 4) monobactams; aztreonam, 5) aminoglycosides; amikacin, gentamicin, tobramycin, 6) other; fosfomycin. Oral antibiotics: 1) ciprofloxacin, 2) trimethoprim-sulfamethoxazole, 3) amoxicillin or amoxicillin/clavulanic acid provided that the isolated E. coli is determined susceptible according to the EUCAST-breakpoint for systemic infections, i.e., MIC ≤ 8 mg/l, and high dosing is used (≥750 mg amoxicillin x 3 and ≥750 mg amoxicillin/125 mg clavulanic acid x 3, respectively) and 4) tebipenem (if approved by the EMA).
• Signed informed consent.

You may not qualify if:

• Adequate intravenous antibiotic treatment for \> 4 days prior to randomization or other adequate (microbiologically active) oral antibiotic treatment for the same fUTI episode prior to recruitment.
• Growth of other bacterial species than E. coli, or fungi, in urine.
• Contraindication for pivmecillinam (e.g. allergy).
• Clinical suspicion of bacterial prostatitis.
• Renal abscess.
• Kidney transplant.
• Myelosuppressive disorder with neutrophil count \< 0.5 x 10(9)/L at randomization.
• Planned antibiotic treatment for fUTI \> 14 days.
• Likely to be prescribed antibiotic prophylaxis after treatment.
• Other intravenous or oral antibiotic treatment; ongoing or planned during the follow-up period (i.e. until 28 days after EOT for fUTI).
• Severe renal impairment (eGFR \< 20 mL/min) at randomization.
• Morbid obesity (BMI \> 40 kg/m2).
• Pregnancy or breastfeeding.
• Unlikely to follow instructions or the study protocol.
• Previous participation in the study.

Sponsors & Collaborators

• Uppsala University: lead
• The Swedish Research Council: collaborator
• Uppsala Clinical Research Center, Sweden: collaborator

Study Sites (13)

Haukeland University Hospital

Haukeland, Norway

NOT YET RECRUITING

Oslo University Hospital

Oslo, Norway

NOT YET RECRUITING

Södra Älvsborg Hospital

Borås, Sweden

NOT YET RECRUITING

Eskilstuna Hospital

Eskilstuna, Sweden

NOT YET RECRUITING

Sahlgrenska University Hospital

Gothenburg, Sweden

RECRUITING

Blekinge Hospital

Karlskrona, Sweden

NOT YET RECRUITING

Skåne University Hospital

Lund, Sweden

NOT YET RECRUITING

Örebro University Hospital

Örebro, Sweden

RECRUITING

Karolinska University Hospital

Stockholm, Sweden

NOT YET RECRUITING

Sundsvall Hospital

Sundsvall, Sweden

NOT YET RECRUITING

Umeå University Hospital

Umeå, Sweden

NOT YET RECRUITING

Uppsala University Hospital

Uppsala, Sweden

RECRUITING

Central Hospital Växjö

Vaxjo, Sweden

NOT YET RECRUITING

MeSH Terms

Conditions

Urinary Tract Infections; Escherichia coli Infections

Interventions

Amdinocillin Pivoxil; Standard of Care

Condition Hierarchy (Ancestors)

Infections; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Enterobacteriaceae Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses

Intervention Hierarchy (Ancestors)

Amdinocillin; Penicillins; beta-Lactams; Lactams; Amides; Organic Chemicals; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Thomas Tängdén, MD, Professor

  Department of Medical Sciences, Uppsala University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Thomas Tängdén, MD, Professor

CONTACT

+46 708 370323; thomas.tangden@medsci.uu.se

Lisa Faxén, MD, PhD student

CONTACT

+46 768 721806; lisa.faxen@medsci.uu.se

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 14, 2025
• First Posted: November 19, 2025
• Study Start: December 1, 2025
• Primary Completion (Estimated): March 1, 2029
• Study Completion (Estimated): March 1, 2029
• Last Updated: December 17, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

NO (2); SE (11)