Three versus five days of pivmecillinam for community-acquired uncomplicated lower urinary tract infection: A randomised, double-blind, placebo-controlled superiority trial

Filip Jansåker; Sara Thønnings; Frederik Boëtius Hertz; Thomas Kallemose; Jan Værnet; Lars Bjerrum; Thomas Benfield; Niels Frimodt-Møller; Jenny Dahl Knudsen

doi:10.1016/j.eclinm.2019.06.009

Three versus five days of pivmecillinam for community-acquired uncomplicated lower urinary tract infection: A randomised, double-blind, placebo-controlled superiority trial

EClinicalMedicine. 2019 Jul 20:12:62-69. doi: 10.1016/j.eclinm.2019.06.009. eCollection 2019 Jul.

Authors

Filip Jansåker^{1

2

3}, Sara Thønnings^{1

3}, Frederik Boëtius Hertz¹, Thomas Kallemose⁴, Jan Værnet⁵, Lars Bjerrum⁶, Thomas Benfield^{2

7}, Niels Frimodt-Møller^{1

8}, Jenny Dahl Knudsen^{1

8}

Affiliations

¹ Department of Clinical Microbiology, Hvidovre Hospital, Copenhagen University Hospital, Kettegård Allé 30, 2650 Hvidovre, Denmark.
² Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.
³ Analytical BioSciences, Department of Pharmacy, University of Copenhagen, Copenhagen, 2200 Copenhagen, Denmark.
⁴ Clinical Research Centre, Copenhagen University Hospital, Kettegård Allé 30, 2650 Hvidovre, Denmark.
⁵ General Practice, AmagerCentrets Læger, Reberbanegade 3, 2300, Copenhagen, Denmark.
⁶ Section of General Practice and Research Unit of General Practice, Department of Public Health, University of Copenhagen, Oester Farimagsgade 5, 1014, Copenhagen, Denmark.
⁷ Department of Infectious Diseases, Hvidovre Hospital, Copenhagen University Hospital, Kettegård Allé 30, 2650 Hvidovre, Denmark.
⁸ Department of Clinical Microbiology, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark.

Abstract

Background: To investigate if a 5-day course pivmecillinam (amdinocillin pivoxil) 400 mg three times daily is superior to a 3-day course in women with uncomplicated urinary tract infection (UTI).

Methods: A randomised, double-blind, placebo-controlled trial conducted at nine primary care centres in Denmark. 368 women (18-70 years) with symptoms compatible with UTI were randomised to blinded therapy of 5 days [5d] or 3 days followed by 2 days of placebo [3d] from May 2015 to November 2017. Clinical data were assessed using a validated questionnaire at inclusion (day-0), daily the following 7 days and once again within the 2nd to 6th week after intervention. Bacteriological data were collected prior to intervention and twice between day 7 and 42. Main clinical endpoints were days to symptom resolution within 7 days after inclusion and proportions with clinical success at the end of intervention. Main bacteriological endpoint was proportion of participants with significant reduction of bacteriuria (≥ 10² CFU/mL) in 1st control urine sample. ClinicalTrialsRegister.eu: 2014-001321-32.

Findings: 180 (5d) and 188 (3d) participants were included in the study (mean age: 35.4 [5d] and 34.9 [3d]). Of these, 125 (70% [5d]) and 122 (66% [3d]) had a positive baseline urine culture. Forty-four participants were lost to follow-up, leaving 161 [5d] and 163 [3d] participants for analysis, respectively. Mean time to symptom resolution was 2.91 (SD 1.46; [5d]) days and 2.94 (SD 1.42; [3d]) days (P = .894). Clinical success at the end of treatment occurred for 117 of 153 (76%) receiving the 5d-course and for 115 of 157 (73%) receiving the 3d course (difference 3.2% [95% CI -7.1% - 13.5%]; P = .601). Bacteriological success was seen in 92 of 104 (88%) participants given the 5d course and in 86 of 99 (87%) given the 3d course (difference 1.6% [95% CI -8.4%-11.6%]; P = .895).

Interpretations: A 5-day course of pivmecillinam was not superior to a 3-day course in clinical or bacteriological outcomes for UTI.

Primary funding source: The Danish Regions [no. 14/217].

Keywords: AUC; Amdinocillin pivoxil; Cystitis; Pivmecillinam; RCT; UTI.