Alternative antibiotics to multidrug-resistant UTIs

Start 17 Apr 2023 · Status Ongoing, recruiting · 1 EU/EEA countries · 21 sites · Protocol TPLBIS20

Overview

Sponsor-declared trial summary

Phase Therapeutic use (Phase IV)

Status Ongoing, recruiting

Participants planned 330

Countries 1

Sites 21

Urinary tract infection and/or bacteremia caused by extended spectrum beta-lactamases-producing Enterobacterales

A non-inferiority trial to find a safe per oral step down treatment regimen other than ciprofloxacin and Trimetoprim-sulfamethoxazole in febrile UTIs caused by ESBL-producing Enterobacterales (EPE).

Key facts

Sponsor: Region Skane
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: 17 Apr 2023 → ongoing
Decision date (initial): 2024-10-28
Transition trial: Yes
Low-intervention: No
Rare-disease indication: No
Vulnerable population: No
Funding sources: Swedish Society of Medicine · Tegger foundation · Stig and Ragna Gorthon foundations

External identifiers

EU CT number: 2024-513294-41-00
EudraCT number: 2020-005738-13
ClinicalTrials.gov: NCT05224401

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

A non-inferiority trial to find a safe per oral step down treatment regimen other than ciprofloxacin and Trimetoprim-sulfamethoxazole in febrile UTIs caused by ESBL-producing Enterobacterales (EPE).

Secondary objectives 3

Growth of EPE in follow up urine culture (microbiological endpoint) at TOC.
Faecal culture positive for EPE at follow up at TOC.
Death from all causes within 28 days.

Conditions and MedDRA coding

Urinary tract infection and/or bacteremia caused by extended spectrum beta-lactamases-producing Enterobacterales

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

Adult men and women (> 18 years) with urine and/or blood culture positive for EPE. Thus, intravenous antibiotics must have been started for patients to be included.
Patient has received in patient care with 1-5 days of intravenous treatment with empirical antibiotics. The treating physician has considered per oral treatment safe.
Fever (≥ 38.0 C at least once at home or at hospital) at the emergency room (ER). Per oral therapy can be initiated regardless of temperature.
Clinical suspicion of UTI at the ER. The latter is suspected due to at least one of the following symptoms: flank pain, dysuria, positive dipstick analysis, or percussion tenderness over kidneys.
Informed consent is signed by patient.
Discontinuing parenteral treatment and starting treatment with per oral antibiotics is considered safe according to treating physician.

Exclusion criteria 4

Known/suspected beta-lactam allergy.
Clinical isolate of EPE is pivmecillinam-resistant
Pregnancy
Other reason, according to treating physician, to which patient is unfit to be included in the study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

Clinical response 7 to 10 days (test of cure, TOC) after antibiotic treatment has been discontinued. The primary endpoint is met if the patient has no symptoms (i.e. resolution of fever and dysuria > 24 h) and no further antibiotic treatment is necessary, as determined by treating physician.

Secondary endpoints 3

Growth of EPE in follow up urine culture (microbiological endpoint) at TOC.
Faecal culture positive for EPE at follow up at TOC.
Death from all causes within 28 days.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Selexid 400 mg filmdragerade tabletter

PRD7199131 · Product

Active substance: Pivmecillinam Hydrochloride
Pharmaceutical form: FILM-COATED TABLET
Route of administration: ORAL
Max daily dose: 1200 mg milligram(s)
Max total dose: 10800 mg milligram(s)
Max treatment duration: 9 Week(s)
Authorisation status: Authorised
ATC code: J01CA08 — PIVMECILLINAM
Marketing authorisation: 43371
MA holder: KARO PHARMA AB
MA country: Sweden
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Amoxicillin/Clavulanic acid Aurobindo 500 mg/125 mg filmdragerade tabletter

PRD5677405 · Product

Active substance: Amoxicillin
Pharmaceutical form: FILM-COATED TABLET
Route of administration: ORAL
Max daily dose: 1500 mg milligram(s)
Max total dose: 13500 mg milligram(s)
Max treatment duration: 9 Day(s)
Authorisation status: Authorised
ATC code: J01CR02 — AMOXICILLIN AND ENZYME INHIBITOR
Marketing authorisation: 42590
MA holder: AUROBINDO PHARMA (MALTA) LIMITED
MA country: Sweden
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Comparator 3

Ciprofloxacin Orion 500 mg filmdragerade tabletter

PRD1644875 · Product

Active substance: Ciprofloxacin
Pharmaceutical form: FILM-COATED TABLET
Route of administration: ORAL
Max daily dose: 1000 mg milligram(s)
Max total dose: 9000 mg milligram(s)
Max treatment duration: 9 Day(s)
Authorisation status: Authorised
ATC code: J01MA02 — CIPROFLOXACIN
Marketing authorisation: 23576
MA holder: ORION CORPORATION
MA country: Finland
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Eusaprim forte 160 mg/800 mg tabletter

PRD981331 · Product

Active substance: Sulfamethoxazole
Pharmaceutical form: TABLET
Route of administration: ORAL
Max daily dose: 1600 mg milligram(s)
Max total dose: 14400 mg milligram(s)
Max treatment duration: 9 Day(s)
Authorisation status: Authorised
ATC code: J01EE01 — SULFAMETHOXAZOLE AND TRIMETHOPRIM
Marketing authorisation: 9263
MA holder: ASPEN PHARMA TRADING LIMITED
MA country: Sweden
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Ertapenem Fresenius Kabi 1 g pulver till koncentrat till infusionsvätska, lösning

PRD9228830 · Product

Active substance: Ertapenem
Pharmaceutical form: SOLUTION FOR INFUSION
Route of administration: INTRAVENOUS
Max daily dose: 1 g gram(s)
Max total dose: 9 g gram(s)
Max treatment duration: 9 Week(s)
Authorisation status: Authorised
ATC code: J01DH03 — -
Marketing authorisation: 33989
MA holder: FRESENIUS KABI AB
MA country: Finland
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Region Skane

Sponsor organisation: Region Skane
Address: Dockplatsen 26, Malmo S:t Petri Malmo S:t Petri
City: Malmo
Postcode: 211 74
Country: Sweden

Scientific contact point

Organisation: Region Skane
Contact name: Oskar Ljungquist

Public contact point

Organisation: Region Skane
Contact name: Oskar Ljungquist

Third parties 1

Organisation	City, country	Duties
Region Skane Skanes Universitetssjukhus ORG-100011290	Lund, Sweden	On site monitoring, Data management

Locations

1 EU/EEA country · 21 investigational sites

By country

Country	MS status	Planned subjects	Sites
Sweden	Ongoing, recruiting	330	21
Rest of world	—	0	—

Investigational sites

Sweden

21 sites · Ongoing, recruiting

Region Skane Helsingborg Hospital

Infektionsenheten, Charlotta Yhléns gata 10, Helsingborg, Charlotte Yhlens Gata 10, Helsingborgs Maria, Helsingborg

Region Skane Skanes Universitetssjukhus

VO infektion, Ruth Lundskogs gata 3, Malmö, St. Johns, Fritz Bauers Gata 5, Malmo

Region Skane Skanes Universitetssjukhus

VO Infektion, Hälsogatan 3, SUS, 221 85 Lund, Entregatan 7, 222 42, Lund

Region Vaermland

Infektionskliniken, Centralsjukhuset Karlstad, Rosenborgsgatan 50, 652 33, Karlstad

Region Vaestmanland

Infektionsenheten, Sigtunagatan, Västmanlands sjukhus Västerås, Sigtunagatan, 721 89, Vasteras

Malarsjukhuset Eskilstuna

Infektion, Entré 11, Björnströmsgatan 6, Mälarsjukhuset Eskilstuna, Kungsvagen 42, Tunafors, Eskilstuna

Laenssjukhuset I Kalmar Region Kalmar Laen

Infektionsmottagning, Lasarettsvagen 8, Kalmar S:t Johannes, Kalmar

Capio S:t Goerans Sjukhus AB

Infektion, S:t Göransplan 1, Stockholm, Sankt Goransplan 1, Vastermalm, Stockholm

Region Skane Kristianstad Central Hospital

VO Infektion, Infektionsmottagning, Ambulansvägen 4, 29185 Kristianstad, J A Hedlunds Vag 5, Kristianstads Heliga Trefaldighet, Kristianstad

Region Jaemtland Haerjedalen

Östersunds sjukhus, Kyrkgatan 12, 831 50 Östersund, Infektionskliniken, Kyrkgatan 12, 831 50, Ostersund

Region Gaevleborg

Gävle sjukhus, Infektion, Lasarettsvägen 1, 801 88 Gävle, Rektorsgatan 1, 802 50, Gavle

Sodra Alvsborg Hospital Vastra Gotalandsregionen

Infektionsenheten, Södra Älvsborgs sjukhus, Samaritvägen 1, Borås, Bramhultsvagen 53, Boras Gustav Adolf, Boras

Skaraborg Hospital-Vastra Gotalandsregionen

Infektionsmottagning, Lövängsvägen 10, Skövde, Lovangsvagen 1, 541 42, Skovde

Region Halland

Infektion, Hallands Sjukhus Halmstad, 30185 Halmstad, Lasarettsvagen 1, 302 33, Halmstad

Region Norrbotten

Infektionskliniken, Sunderby sjukhus, Sjukhusvägen 10, 971 80 Luleå, Robertsviksgatan 7, Lulea Domkyrkofors., Lulea

Region Gotland

Infektion, Visby lasarett, S:t Goransgatan 5, Visby Domkyrkofors., Visby

Region Oestergoetland

Infektionskliniken i Östergötland, Universitetssjukhuset I, 58185, Linkoping

Vrinnevisjukhuset I Norrkoeping Region Oestergoetland

Infektionskliniken i Östergötland, S Borg, Gamla Ovagen 25, Norrkoping

Region Vaesternorrland

Sundsvalls sjukhus, Lasarettsvägen 21, 856 43 Sundsvall, Infektionskliniken, Lasarettsvagen 21, 856 43, Sundsvall

NU Hospital Group-Vaestra Goetalandsregionen

Uddevalla Sjukhus, Infektionskliniken, Larketorpsvagen, 461 85, Trollhattan