Clinical Trial Results:
Three versus five days of pivmecillinam 400 mg three times daily for community-acquired uncomplicated lower urinary tract infection: A randomised, double-blind, placebo-controlled superiority trial
Summary
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EudraCT number |
2014-001321-32 |
Trial protocol |
DK |
Global end of trial date |
22 Dec 2017
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Results information
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Results version number |
v1(current) |
This version publication date |
18 Dec 2019
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First version publication date |
18 Dec 2019
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Other versions |
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Summary report(s) |
Summary |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
198809
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Department of Clinical Microbiology
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Sponsor organisation address |
Kettegård allé, Hvidovre, Denmark, 2650
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Public contact |
Department of Clinical Microbiology, Department of Clinical Microbiology, Hvidovre Hospital, 0045 36322428, Inge.Jenny.Dahl.Knudsen@regionh.dk
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Scientific contact |
Department of Clinical Microbiology, Department of Clinical Microbiology, Hvidovre Hospital, 0045 36322428, Inge.Jenny.Dahl.Knudsen@regionh.dk
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
12 Apr 2018
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
31 Oct 2017
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Global end of trial reached? |
Yes
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Global end of trial date |
22 Dec 2017
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
Identify and compare the efficacy of pivmecillinam 400 mg t.i.d in a 3-day respectively 5-day regimen, against community acquired lower urinary tract infections i.e. in women at the age of 18-70 years old.
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Protection of trial subjects |
Diagnosis, treatment and management according to national guidelines for uncomplicated cystitis in primary care settings.
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Background therapy |
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Evidence for comparator |
- | ||
Actual start date of recruitment |
01 Jul 2015
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Denmark: 368
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Worldwide total number of subjects |
368
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EEA total number of subjects |
368
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
366
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From 65 to 84 years |
2
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85 years and over |
0
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Recruitment
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Recruitment details |
See open acces protocol and open acces manuscript publication: MANUSCRIPT: https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(19)30102-6/fulltext Jansaker F, et al. 2019. eClinicalMedicine PROTOCOL: https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-016-2022-0 Jansaker F, et al. 2016. BMC inf dis. | |||||||||||||||
Pre-assignment
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Screening details |
PROTOCOL: https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-016-2022-0 Jansaker F, et al. 2016. BMC inf dis. | |||||||||||||||
Period 1
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Period 1 title |
12-05-2015 to 31-10-2017 (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Data analyst, Carer, Assessor | |||||||||||||||
Blinding implementation details |
See open acces protocol and open acces manuscript publication:
MANUSCRIPT: https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(19)30102-6/fulltext
Jansaker F, et al. 2019. eClinicalMedicine
PROTOCOL: https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-016-2022-0
Jansaker F, et al. 2016. BMC inf dis.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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3-day | |||||||||||||||
Arm description |
3 days of pivmecillinam 400 mg three times daily followed by two days of placebo (identical to pivmecillinam i coat, packing, color and look). Danish guidelines at the time. | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
pivmecillinam
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Investigational medicinal product code |
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Other name |
pivmecillinam
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
400 mg tablet three times daily every 8th hour
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Arm title
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5-day | |||||||||||||||
Arm description |
5 days of pivmecillinam 400 mg three times daily | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
pivmecillinam
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Investigational medicinal product code |
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Other name |
pivmecillinam
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
400 mg tablet three times daily every 8th hour
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Baseline characteristics reporting groups
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Reporting group title |
3-day
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Reporting group description |
3 days of pivmecillinam 400 mg three times daily followed by two days of placebo (identical to pivmecillinam i coat, packing, color and look). Danish guidelines at the time. | ||||||||||||||||||||||||||||||||||||||||
Reporting group title |
5-day
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Reporting group description |
5 days of pivmecillinam 400 mg three times daily | ||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Analysed
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Subject analysis set type |
Per protocol | ||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
368 women (18–70 years)
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End points reporting groups
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Reporting group title |
3-day
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Reporting group description |
3 days of pivmecillinam 400 mg three times daily followed by two days of placebo (identical to pivmecillinam i coat, packing, color and look). Danish guidelines at the time. | ||
Reporting group title |
5-day
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Reporting group description |
5 days of pivmecillinam 400 mg three times daily | ||
Subject analysis set title |
Analysed
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
368 women (18–70 years)
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End point title |
Primary Clinical Outcome, Bacterial Outcome [1] | |||||||||
End point description |
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).
Mean time to symptom resolution was 2.91 (SD 1.46; [5d]) days and 2.94 (SD 1.42; [3d]) days (P = .894).
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).
Please see final publication in open access journal for full details, supplementary data och RAW data fully available.
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End point type |
Primary
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End point timeframe |
Clinical cure after end of intervention (i.e. five days therapy).
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: For correct and to minimize risk of incorrect translation, please see statistical plan and statistical method under open access publication, which is done and written by professional statistican, which the uploader is not. https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(19)30102-6/fulltext (full article) https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(19)30102-6/fulltext#secst0215 (here you find the statistical descriptions; supplementary data to article) |
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
See open acces protocol and open acces manuscript publication:
MANUSCRIPT: https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(19)30102-6/fulltext
Jansaker F, et al. 2019. eClinicalMedicine
PROTOCOL: https://bmcinfectdis.biomedcentral.com/
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Adverse event reporting additional description |
Appendix Table 8 in open acces manuscript publication:
MANUSCRIPT: https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(19)30102-6/fulltext
Jansaker F, et al. 2019. eClinicalMedicine
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
Selexid label 2015 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
1
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Reporting groups
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Reporting group title |
Adverse events
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Reporting group description |
Appendix Table 8 in open acces manuscript publication: MANUSCRIPT: https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(19)30102-6/fulltext Jansaker F, et al. 2019. eClinicalMedicine "A total of 306 participants reported on adverse events in the diary (Appendix Table 8). There were no serious adverse events and no reported cases of Clostridium difficile associated diarrhoea" | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
See discuss section in open acces manuscript publication: MANUSCRIPT: https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(19)30102-6/fulltext Jansaker F, et al. 2019. eClinicalMedicine | |||
Online references |
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http://www.ncbi.nlm.nih.gov/pubmed/31388664 |