Clinical trial • Phase IV • Infectious Disease

PIVMECILLINAM HYDROCHLORIDE for Complicated urinary tract infection (cUTI)

Phase IV trial of PIVMECILLINAM HYDROCHLORIDE for Complicated urinary tract infection (cUTI).

Overview

Trial Therapeutic Area
Infectious Disease
Trial Disease
Complicated urinary tract infection (cUTI)
Trial Stage
Phase IV
Drug Modality
Small molecule

Key dates

Initial CTIS Submission Date
25-11-2025
First CTIS Authorization Date
27-03-2026

Trial design

Randomised, open-label, piperacillin/tazobactam: iv piperacilin/tazobactam 4.0/0.5 g every 8 hours; ampicillin plus gentamicin: iv ampicillin 2 g every 6 hours + iv gentamicin (5 mg/kg first dose, adjusted thereafter, every 24 hours for up to 3 days); pivmecillinam plus single dose gentamicin (interventional arm): oral pivmecillinam 800 mg every 8 hours + single iv gentamicin 5 mg/kg-controlled Phase IV trial across 7 sites in Denmark.

Randomised
Yes
Open Label
Yes
Comparator
Piperacillin/tazobactam: iv piperacilin/tazobactam 4.0/0.5 g every 8 hours; Ampicillin plus gentamicin: iv ampicillin 2 g every 6 hours + iv gentamicin (5 mg/kg first dose, adjusted thereafter, every 24 hours for up to 3 days); Pivmecillinam plus single dose gentamicin (interventional arm): Oral pivmecillinam 800 mg every 8 hours + single iv gentamicin 5 mg/kg
Target Sample Size
618
Trial Duration For Participant
365

Eligibility

Recruits 618 No vulnerable populations selected; only adults (≥18) are eligible. Informed consent is required prior to inclusion (Exclusion criterion: 'Informed consent prior to inclusion unobtainable.'). Subject information and informed consent documents are provided..

Pregnancy Exclusion
Pregnancy or breastfeeding
Vulnerable Population
No vulnerable populations selected; only adults (≥18) are eligible. Informed consent is required prior to inclusion (Exclusion criterion: 'Informed consent prior to inclusion unobtainable.'). Subject information and informed consent documents are provided.

Inclusion criteria

  • {"criterion_text":"- Age ≥18 years\n- Hospitalised with symptoms and/or signs of acute pyelonephritis or lower cUTI\n- Empirical intravenous antibiotic treatment is planned by the treating physician"}

Exclusion criteria

  • {"criterion_text":"- quick Sequential Organ Failure Assessment Score (qSOFA) ≥2 (qSOFA score allocates one point for each of the following criteria: respiratory rate ≥22/min, altered mental status, and systolic blood pressure ≤100 mmHg)\n- Receipt of iv antibiotics covering cUTI prior to enrollment\n- Kidney transplant recipients or patients on hemodialysis or periotoneal dialysis\n- Informed consent prior to inclusion unobtainable.\n- estimated Glomerular Filtration Rate <30ml/min/1.73m^2\n- Urine culture within 72 hours showing a microorganism resistant to one of the study regimens\n- Known allergy or hypersensitivity to pivmecillinam, penicillins, cephalosporins, aminoglycosides or excipients\n- Pregnancy or breastfeeding\n- Inability to ingest oral medication\n- Known myasthenia gravis\n- Acute mononucleosis or porphyria\n- Pre-existing complicated urogenital conditions\n- Current or earlier treatment with cisplatin and/or carboplatin\n- Descent from the Faroe Islands without prior negative screening for Carnitine Transporter Deficiency (CTD)"}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Clinical cure on day 3 (resolution of cUTI-related symptoms and fever, together with clinical improvement and no need for escalating systemic antimicrobial therapy)","definition_or_measurement_approach":"Resolution of cUTI-related symptoms and fever, together with clinical improvement and no need for escalating systemic antimicrobial therapy (assessed on Day 3)"}

Secondary endpoints

  • {"endpoint_text":"- 30/90/365-day mortality\n- Microbiological cure on Day 3\n- Time to oral-only antibiotic therapy\n- Length of hospital stay\n- Antibiotic treatment duration (combined iv and oral)\n- Nephrotoxicity within 30 days\n- Proportion of treatment-related serious adverse reactions (SAE) and suspected unexpected serious adverse reactions (SUSAR)\n- Secondary infections (C. difficile or genital/oral Candida within 30 days of enrollment)\n- Hospital readmission within 90 days due to UTI\n- Post-discharge antibiotic prescription redemption within 90 days for UTI associated antibiotics.","definition_or_measurement_approach":"Mortality measured at Days 30, 90 and 365; Microbiological cure = eradication of baseline uropathogens on Day 3; Time to oral-only therapy, length of stay, total antibiotic duration (iv + oral), nephrotoxicity within 30 days, rates of SAE/SUSAR, secondary infections within 30 days, hospital readmission within 90 days, and post-discharge antibiotic prescription redemption within 90 days."}

Recruitment

Planned Sample Size
618
Recruitment Window Months
32
Consent Approach
Informed consent required from participants prior to inclusion; participants are adults (≥18). Subject information and informed consent forms are provided (documents listed: 'TRI_AB Deltagerinformation', 'S1_informed consent', and related consent documents). No mention of assent or specific languages in the available records.

Geography

Total Number Of Sites
7
Total Number Of Participants
618

Denmark

Earliest CTIS Part Ii Submission Date
17-02-2026
Latest Decision Or Authorization Date
27-03-2026
Processing Time Days
38
Number Of Sites
7
Number Of Participants
618

Sites

Site Name
Esbjerg Og Grindsted Sygehus
Department Name
Emergency department
Contact Person Name
Peter Biesenbach
Contact Person Email
Peter.biesenbach@rsyd.dk
Site Name
Odense University Hospital (Svendborg)
Department Name
Internal Medicine
Contact Person Name
Sandra Dröse
Contact Person Email
Sandra.Droese@rsyd.dk
Site Name
Hospital Sønderjylland
Department Name
Emergency department
Contact Person Name
Christian Backer Mogensen
Contact Person Email
cbm1@rsyd.dk
Site Name
Herlev Hospital
Department Name
Emergency department
Contact Person Name
Kasper Karmark Iversen
Site Name
Lillebaelt Hospital
Department Name
Internal Medicine
Contact Person Name
Lone Wulff Madsen
Contact Person Email
Lone.Wulff.Madsen@rsyd.dk
Site Name
Hvidovre Hospital
Department Name
Dept. of infectious diseases
Contact Person Name
Thomas Benfield
Site Name
Odense University Hospital (Odense C)
Department Name
Dept. of infectious diseases
Contact Person Name
Isik Somuncu Johansen
Contact Person Email
Isik.Somuncu.Johansen@rsyd.dk

Sponsor

Primary sponsor

Full Name
Odense University Hospital
Organisation Type
Hospital/Clinic/Other health care facility
Country Of Registered Address
Denmark

Third parties

  • {"country":"Denmark","full_name":"Odense University Hospital","duties_or_roles":"sponsorDuties codes: 1,7,8","organisation_type":"Hospital/Clinic/Other health care facility"}

Investigational products

Investigational Product Name
PIVMECILLINAM
Active Substance
PIVMECILLINAM HYDROCHLORIDE
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Authorisation Status
2
Starting Dose
800 mg every 8 hours (oral) as used in trial arm
Dose Levels
max daily amount 2400 mg (doseUom mg)
Frequency
Every 8 hours (three times daily)
Maximum Dose
2400 mg/day
Investigational Product Name
GENTAMICIN
Active Substance
GENTAMICIN SULFATE
Modality
Small molecule
Routes Of Administration
INTRAVENOUS ADMINISTRATION
Route
INTRAVENOUS
Authorisation Status
2
Starting Dose
5 mg/kg IV (single dose in pivmecillinam arm); in ampicillin arm: 5 mg/kg first dose, adjusted thereafter, every 24 hours for up to 3 days
Dose Levels
max daily amount 5 mg/kg (doseUom mg/kg)
Frequency
Single dose or every 24 hours (adjusted) up to 3 days
Maximum Dose
5 mg/kg (per dosing guidance)
Investigational Product Name
AMPICILLIN
Active Substance
AMPICILLIN SODIUM
Modality
Small molecule
Routes Of Administration
INTRAVENOUS ADMINISTRATION
Route
INTRAVENOUS
Authorisation Status
2
Starting Dose
2 g IV every 6 hours (as used in trial arm, given with gentamicin)
Dose Levels
max daily amount 8 g (doseUom g)
Frequency
Every 6 hours
Maximum Dose
8 g/day
Investigational Product Name
PIPERACILLIN AND BETA-LACTAMASE INHIBITOR
Active Substance
PIPERACILLIN SODIUM / TAZOBACTAM SODIUM
Modality
Small molecule
Routes Of Administration
INTRAVENOUS ADMINISTRATION
Route
INTRAVENOUS
Authorisation Status
2
Starting Dose
4.0/0.5 g IV every 8 hours
Dose Levels
max daily amount 16 g (doseUom g)
Frequency
Every 8 hours
Maximum Dose
16 g/day
Combination Treatment
Yes

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