Overview
Sponsor-declared trial summary
Phase
Therapeutic exploratory (Phase II)
Status
Ongoing, recruiting
Participants planned
560
Countries
2
Sites
13
febrile Urinary Tract Infection (fUTI)
The primary objective is to investigate if the clinical response with oral follow-up treatment with pivmecillinam 400 mg QID is non-inferior to standard of care in patients with E. coli fUTI 7 (+/-2) days after end of treatment (EOT).
Key facts
- Sponsor
- Uppsala Universitet
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Bacterial Infections and Mycoses [C01]
- Trial duration
- 13 Nov 2025 → ongoing
- Decision date (initial)
- 2025-10-08
- Transition trial
- No
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- No
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Safety, Efficacy
The primary objective is to investigate if the clinical response with oral follow-up treatment with pivmecillinam 400 mg QID is non-inferior to standard of care in patients with E. coli fUTI 7 (+/-2) days after end of treatment (EOT).
Secondary objectives 7
- Sustained clinical response
- Microbiological response
- Sustained microbiological response
- Adverse events
- Disturbances in the intestinal microbiome
- Pharmacokinetics of mecillinam in plasma and urine
- Cost effectiveness of pivmecillinam
Conditions and MedDRA coding
febrile Urinary Tract Infection (fUTI)
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 6
- ≥18 years of age.
- Diagnosis of fUTI, defined as i) fever ≥ 38°C measured in a healthcare institution 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.
- Signed informed consent.
Exclusion criteria 17
- 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.
- If consenting to microbiome analysis: i) contraindication for ciprofloxacin (e.g. allergy), ii) unlikely to be able to provide fecal samples per protocol, iii) treatment with antibiotics in the past 3 months before the current fUTI episode, iv) chronic intestinal disease or previous surgery in the gastrointestinal tract.
- If consenting to pharmacokinetic analysis: expected difficulties in taking blood and urine samples per protocol.
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- 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 EOT.
Secondary endpoints 7
- Sustained clinical response: i) no new healthcare contacts or antibiotic treatments for suspected or proven UTI, ii) no recurrent fever (≥ 38°C), and iii) no recurrent UTI symptoms after completion of the initial therapy and until 28 (+/- 2) days after EOT.
- Microbiological response: no detectable growth of E. coli in urine sampled at TOC, 7 (+/-2) days after EOT.
- Sustained microbiological response; no detectable growth of E. coli in urine sampled at the second follow-up 28 (+/- 2) days after EOT.
- Occurrence and severity of AEs from start of study treatment until TOC: recorded by the participating patients in a diary, documented in the medical records, or reported at the TOC follow-up.
- Disturbances in the intestinal microbiome: analysed by repeated collection of fecal samples from 30 patients treated with pivmecillinam or ciprofloxacin, respectively.
- Pharmacokinetics of mecillinam in plasma and urine and PK/PD target attainment; assessed by blood and urine sampling from 30 patients treated with pivmecillinam.
- Cost-effectiveness of pivmecillinam as compared with standard of care.
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
SCP192300 · ATC
- Active substance
- Pivmecillinam Hydrochloride
- Route of administration
- ORAL USE
- Max daily dose
- 1.6 g gram(s)
- Max total dose
- 12.8 g gram(s)
- Max treatment duration
- 8 Day(s)
- Authorisation status
- Authorised
- ATC code
- J01CA08 — PIVMECILLINAM
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Comparator 17
SCP108746144 · ATC
- Active substance
- Amikacin Sulfate
- Substance synonyms
- AMIKACIN SULPHATE
- Route of administration
- INFUSION
- Max daily dose
- 30 mg/kg milligram(s)/kilogram
- Max total dose
- 30 mg/kg milligram(s)/kilogram
- Max treatment duration
- 12 Day(s)
- Authorisation status
- Authorised
- ATC code
- J01GB06 — AMIKACIN
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP1153878 · ATC
- Active substance
- Piperacillin Sodium
- Route of administration
- INFUSION
- Max daily dose
- 18 g gram(s)
- Max total dose
- 216 g gram(s)
- Max treatment duration
- 12 Day(s)
- Authorisation status
- Authorised
- ATC code
- J01CR05 — PIPERACILLIN AND BETA-LACTAMASE INHIBITOR
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP1143957 · ATC
- Active substance
- Cefotaxime
- Route of administration
- INFUSION
- Max daily dose
- 12 g gram(s)
- Max total dose
- 144 g gram(s)
- Max treatment duration
- 12 Day(s)
- Authorisation status
- Authorised
- ATC code
- J01DD01 — CEFOTAXIME
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP18113964 · ATC
- Active substance
- Aztreonam
- Route of administration
- INFUSION
- Max daily dose
- 8 g gram(s)
- Max total dose
- 96 g gram(s)
- Max treatment duration
- 12 Day(s)
- Authorisation status
- Authorised
- ATC code
- J01DF01 — AZTREONAM
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP109545371 · ATC
- Active substance
- Amoxicillin Sodium
- Route of administration
- ORAL USE
- Max daily dose
- 3.38 g gram(s)
- Max total dose
- 40.56 g gram(s)
- Max treatment duration
- 12 Day(s)
- Authorisation status
- Authorised
- ATC code
- J01CR02 — AMOXICILLIN AND BETA-LACTAMASE INHIBITOR
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP10319265 · ATC
- Active substance
- Fosfomycin Calcium
- Route of administration
- INFUSION
- Max daily dose
- 24 g gram(s)
- Max total dose
- 288 g gram(s)
- Max treatment duration
- 12 Day(s)
- Authorisation status
- Authorised
- ATC code
- J01XX01 — FOSFOMYCIN
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
—
SCP101105926 · ATC
- Route of administration
- INFUSION
- Max daily dose
- 7 mg/kg milligram(s)/kilogram
- Max total dose
- 7 mg/kg milligram(s)/kilogram
- Max treatment duration
- 12 Day(s)
- Authorisation status
- Authorised
- ATC code
- J01GB01 — TOBRAMYCIN
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP1166462 · ATC
- Active substance
- Cilastatin Sodium
- Route of administration
- INFUSION
- Max daily dose
- 4 g gram(s)
- Max total dose
- 48 g gram(s)
- Max treatment duration
- 12 Day(s)
- Authorisation status
- Authorised
- ATC code
- J01DH51 — IMIPENEM AND CILASTATIN
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP12479042 · ATC
- Active substance
- Ciprofloxacin Hydrochloride
- Route of administration
- ORAL USE
- Max daily dose
- 1.5 g gram(s)
- Max total dose
- 18 g gram(s)
- Max treatment duration
- 12 Day(s)
- Authorisation status
- Authorised
- ATC code
- J01MA02 — CIPROFLOXACIN
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP106376770 · ATC
- Active substance
- Cefuroxime Axetil
- Substance synonyms
- CEFUROXIMAXETIL, CEFUROXIM-AXETIL, CEFUROXIMUM AXETILUM
- Route of administration
- INFUSION
- Max daily dose
- 4.5 g gram(s)
- Max total dose
- 54 g gram(s)
- Max treatment duration
- 12 Day(s)
- Authorisation status
- Authorised
- ATC code
- J01DC02 — CEFUROXIME
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP12505097 · ATC
- Active substance
- Betamethasone Valerate
- Substance synonyms
- BETAMETHASONE 17-VALERATE
- Route of administration
- INFUSION
- Max daily dose
- 7 mg/kg milligram(s)/kilogram
- Max total dose
- 7 mg/kg milligram(s)/kilogram
- Max treatment duration
- 12 Day(s)
- Authorisation status
- Authorised
- ATC code
- J01GB03 — GENTAMICIN
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP10330863 · ATC
- Active substance
- Amoxicillin Sodium
- Route of administration
- ORAL USE
- Max daily dose
- 3 g gram(s)
- Max total dose
- 36 g gram(s)
- Max treatment duration
- 12 Day(s)
- Authorisation status
- Authorised
- ATC code
- J01CA04 — AMOXICILLIN
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP106362797 · ATC
- Active substance
- Ampicillin Sodium
- Route of administration
- INFUSION
- Max daily dose
- 12 g gram(s)
- Max total dose
- 144 g gram(s)
- Max treatment duration
- 12 Day(s)
- Authorisation status
- Authorised
- ATC code
- J01CA01 — AMPICILLIN
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP107121969 · ATC
- Active substance
- Ceftriaxone Sodium
- Route of administration
- INFUSION
- Max daily dose
- 2 g gram(s)
- Max total dose
- 24 g gram(s)
- Max treatment duration
- 12 Day(s)
- Authorisation status
- Authorised
- ATC code
- J01DD04 — CEFTRIAXONE
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP101876674 · ATC
- Active substance
- Linezolid
- Route of administration
- INFUSION
- Max daily dose
- 3 g gram(s)
- Max total dose
- 36 g gram(s)
- Max treatment duration
- 12 Day(s)
- Authorisation status
- Authorised
- ATC code
- J01DH02 — MEROPENEM
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP1166649 · ATC
- Active substance
- Bromhexine Hydrochloride
- Route of administration
- ORAL USE
- Max daily dose
- 2.88 g gram(s)
- Max total dose
- 34.56 g gram(s)
- Max treatment duration
- 12 Day(s)
- Authorisation status
- Authorised
- ATC code
- J01EE01 — SULFAMETHOXAZOLE AND TRIMETHOPRIM
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP109549648 · ATC
- Active substance
- Ertapenem Sodium
- Substance synonyms
- ERTAPENEM MONOSODIUM
- Route of administration
- INFUSION
- Max daily dose
- 1 g gram(s)
- Max total dose
- 12 g gram(s)
- Max treatment duration
- 12 Day(s)
- Authorisation status
- Authorised
- ATC code
- J01DH03 — ERTAPENEM
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Uppsala Universitet
- Sponsor organisation
- Uppsala Universitet
- Address
- P. O. Box 256
- City
- Uppsala
- Postcode
- 751 05
- Country
- Sweden
Scientific contact point
- Organisation
- Uppsala Universitet
- Contact name
- Department of Medical Sciences, Section for Infection Medicine, Thomas Tängdén
Public contact point
- Organisation
- Uppsala Universitet
- Contact name
- Department of Medical Sciences, Section for Infection Medicine, Thomas Tängdén
Locations
2 EU/EEA countries · 13 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Norway | Authorised, recruitment pending | 50 | 2 |
| Sweden | Ongoing, recruiting | 510 | 11 |
| Rest of world | — | 0 | — |
Investigational sites
Oslo University Hospital HF
Dept. of Infectious Diseases, P. O. Box 4953, 0424, Oslo
Helse Bergen HF
Dept. of Infectious Diseases, Haukelandsveien 22, 5021, Bergen
Region Skane Skanes Universitetssjukhus
Infektionsklinken, Entregatan 7, 222 42, Lund
Soedra Aelvsborg Hospital Vaestra Goetalandsregionen
Infektionskliniken, Bramhultsvagen 53, Boras Gustav Adolf, Boras
Region Vaesternorrland
Länssjukhuset Sundsvall-Härnösand, Infektionskliniken, Lasarettsvagen 21, 856 43, Sundsvall
Sahlgrenska University Hospital-Vaestra Goetalandsregionen
Verksamhet Infektion, Diagnosvagen 11, Harlanda, Gothenburg
Region Vaesterbotten
Norrlands Universitetssjukhus, Infektionskliniken, Daniel Naezens Vag, 907 37, Umea
Malarsjukhuset Eskilstuna
Infektionskliniken, Kungsvagen 42, Tunafors, Eskilstuna
Region Kronoberg
Centrallasarettet Växjö, Infektionskliniken, Nygatan 20, Vaxjo Stads- Och Domkyrkofors., Vaxjo
Region Oerebro Laen
Universitetssjukhuset Örebro, VO Infektion, Sodra Grev Rosengatan, 701 85, Orebro
Uppsala University Hospital
Infektionskliniken, Akademiska Sjukhuset, 751 85, Uppsala
Region Blekinge
Blekingesjukhuset, Infektionskliniken, Lasarettsvagen, 371 85, Karlskrona
Karolinska University Hospital
Medicinska Enheten för infektionssjukdomar, Eugeniavagen 3, 171 64, Solna
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Sweden | 2025-11-13 | 2026-02-13 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 41 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol_PIVOT_2023-503447-33 | 3 |
| Protocol (for publication) | D4_Patient Facing Material Pasientdagbok_ PIVOT studie_NOR | 1 |
| Protocol (for publication) | D4_Patient Facing Material Patient diary_ENG | 1 |
| Protocol (for publication) | D4_Patient Facing Material Questionnaire_ENG_ | 1 |
| Protocol (for publication) | D4_Patient Facing material_ENG intag mat och dryck | 1 |
| Protocol (for publication) | D4_Patient Facing_SWE Intag mat och dryck | 1 |
| Protocol (for publication) | D4_Provtagningsinstruktion avf PIVOT ENG | 1 |
| Protocol (for publication) | D4_Provtagningsinstruktion avf PIVOT SWE | 1 |
| Protocol (for publication) | D4_Provtagningsinstruktion urinprov PIVOT ENG | 1 |
| Protocol (for publication) | D4_Provtagningsinstruktion urinprov PIVOT NOR | 1 |
| Protocol (for publication) | D4_Provtagningsinstruktion urinprov PIVOT SWE | 1 |
| Recruitment arrangements (for publication) | K1_Recruitment Arrangements | 1 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements_Norway_OUH Ulleval_ | 2 |
| Subject information and informed consent form (for publication) | L1_PIVOT_Subject Information NOR | 2 |
| Subject information and informed consent form (for publication) | L1_PIVOT_Subject Information_Norway_ENG_ | 1 |
| Subject information and informed consent form (for publication) | L1_Subject information sheet and consent_ Main Study | 1 |
| Subject information and informed consent form (for publication) | L1_Subject information sheet and consent_ Main Study_ENG | 1 |
| Subject information and informed consent form (for publication) | L1_Subject information sheet and consent_ SubStudy Mikrobiota | 1 |
| Subject information and informed consent form (for publication) | L1_Subject information sheet and consent_ SubStudy Mikrobiota_ENG | 1 |
| Subject information and informed consent form (for publication) | L1_Subject information sheet and consent_ SubStudy PK | 1 |
| Subject information and informed consent form (for publication) | L1_Subject information sheet and consent_ SubStudy PK_ENG_ | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_amikacin | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_amoxicillin | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_amoxicillin clavulanic acid | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_ampicillin_NO | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_aztreonam_NO | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_cefotaxim | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_ceftriaxon | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_cefuroxim | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_ciprofloxacin_NO | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_ertapenem | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_fosfomycin_SE | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_gentamicin | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_imipenem_NO | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_meropenem | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_piperacillin tazobactam | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_pivmecillinam_SE | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_tobramycin_NO | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_trimethoprim sulfamethoxazole_NO | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol Synopsis_NOR_PIVOT-2023-503447-33 | 3 |
| Synopsis of the protocol (for publication) | D1_Protocol_Synopsis SWE PIVOT-2023-503447-33 | 3 |
Application history
1 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2025-06-23 | Sweden | Acceptable 2025-10-06
|
2025-10-06 |