Treating Pyelonephritis an Urosepsis With Pivmecillinam

NCT03282006 — Phase 4, Completed, 53 participants, Sykehuset i Vestfold HF

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The Efficacy and Safety of Pivmecillinam in Treating Bacteriemic Urosepsis Caused by E.Coli

Registry	NCT03282006, acronym MePUr
Status	Completed
Phase	Phase 4
Study type	Interventional; na, single group, masking: none, treatment
Enrollment	53 (Actual)
Sponsor	Sykehuset i Vestfold HF (Other); collaborators: University of Oslo
Conditions	Pyelonephritis, Urinary Tract Infections
Interventions	pivmecillinam (Drug)
Dates	start 2017-09-29, primary completion 2020-04-21, completion 2020-04-21, first posted 2017-09-13, last updated 2020-04-22
Locations	1 site in Norway

-Summary

Febrile urinary tract infections and urosepsis are common and potentially serious infections that require effective antimicrobial treatment. The duration of parenteral treatment depends on oral alternatives. These alternatives are few and due to antimicrobial resistance, quinolones are "standard of care". The increased use of quinolones is concerning because of its negative ecological aspects and it is confirmed an increasing incidence of resistant E.coli to quinolones in Norwegian isolates.

Pivmecillinam is an antibiotic with high susceptibility to E.coli but the evidence for treating febrile urinary tract infections is insufficient. This trial will investigate the efficacy and safety of pivmecillinam in treating pyelonephritis and urosepsis caused by E.coli.

The hypothesis is that urosepsis can safely be treated with pivmecillinam when it is given after 2-3 days with empirical i.v. antibiotics.

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+Detailed description

This trial will be conducted at Vestfold Hospital, Norway, and is a prospective observational study with intention to treat. Participants will be consecutively included among hospitalized patients suffering from urosepsis - see eligibility criteria. After 3 days with parenteral antibiotics, when clinical improvement and absence of fever/leukocytosis is confirmed, the participants will start on pivmecillinam 400mg four times daily and be discharged. Pivmecillinam is to be taken for one week. The participants will be contacted by phone on day 4, 10 and 33 (days after admission). On day 17 (test of cure, TOC) they will meet for physical examination. They will report symptom score (standardized schema) on day 0, and 17. Urine samples will be collected on day 10 and 17. Blood samples on day 17. All data will be stored anonymously. The trial will be monitored by extern resources.

+Arms and interventions

Arm	Type	Interventions	Description
Pivmecillinam	Experimental	Drug: pivmecillinam	Patients treated with pivmecillinam

pivmecillinam (Drug), also known as Selexid, Penomax: Oral treatment of bacteremic pyelonephritis following standard initial parenteral treatment

+Outcome measures

Primary outcomes

Clinical efficacy [Day 17]: Defined as abscence of fever, no need for other antibiotics than prescribed and improvement of symptoms (self-reported improvement and EQ 5D VAS-scale).

Secondary outcomes

C-reactive protein-level (CRP) [Day 17]: Compare CRP-level on day 0 with day 17.
Readmission due to urinary tract infection (UTI) [Day 33]: Check if participants are readmitted due to UTI.
Readmission - any cause [Day 33]: Check if participants have been readmitted to hospital
Adverse effects [Day 33]: Registrate frequency of rash/skin problems, abdominal pain, clostridium difficile associated diarrhea
Microbial efficacy [Day 17]: Defined as <1.000 CFU E.coli in urine

+Eligibility

Sex: All, ages: 18 Years to 110 Years

Inclusion Criteria:

* E.coli in blood culture
* AND identical isolate in urine sample (>= 1.000 CFU) OR relevant clinical signs of UTI

Exclusion Criteria:

* Bacterial infection origin from another organ (e.g. pneumonia)
* Severe sepsis with multiorgan failure
* Perinephritic abscess
* Pyonephrosis requiring drainage
* Allergy to pivmecillinam
* E.coli isolate resistant to pivmecillinam
* Pregnancy/breastfeeding
* Severe neutropenia
* Prostatitis
* Severe kidney failure (eGFR<15 ml/min)
* Using valproate

+Locations (1)

Facility	City	Country	Status
Vestfold Hospital Trust	Tønsberg, Vestfold	Norway

+Publications

Results publication: Hansen BA, Grude N, Lindbaek M, Stenstad T. The efficacy of pivmecillinam in oral step-down treatment in hospitalised patients with E. coli bacteremic urinary tract infection; a single-arm, uncontrolled treatment study. BMC Infect Dis. 2022 May 19;22(1):478. doi: 10.1186/s12879-022-07463-7. PMID 35590284

+Investigators

Tore Stenstad, MD, PhD, Principal investigator, The Hospital of Vestfold

+Funding

NIH grants: 2016

My Notes

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