Clinical Trial Results:
Carriage of 3GCREB in patients at risk for relapsing infection: randomized controlled trial of intestinal decolonization with colistin plus rifaximin.
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Summary
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EudraCT number |
2014-000180-41 |
Trial protocol |
DE |
Global end of trial date |
02 Dec 2016
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Results information
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Results version number |
v1(current) |
This version publication date |
03 Sep 2020
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First version publication date |
03 Sep 2020
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Other versions |
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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 |
P000176
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
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Other trial identifiers |
German Clinical Trials Register: DRKS00006330 | ||
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Sponsors
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Sponsor organisation name |
Medical Center - University of Freiburg
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Sponsor organisation address |
Breisacher Str. 153, Freiburg, Germany, 79110
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Public contact |
Clinical Trial Information, Clinical Trials Unit of the Medical Center - University of Freiburg, 49 761270-73800, andrea.kunzmann@uniklinik-freiburg.de
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Scientific contact |
Clinical Trial Information, Clinical Trials Unit of the Medical Center - University of Freiburg, 49 761270-73800, andrea.kunzmann@uniklinik-freiburg.de
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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 |
02 Dec 2016
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
02 Dec 2016
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Global end of trial reached? |
Yes
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Global end of trial date |
02 Dec 2016
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
To assess whether decolonization treatment with oral non-absorbable drugs is superior to watch & wait in eradicating 3GCREB from the intestinal tract and prevent infection
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Protection of trial subjects |
The underlying principles for the independent Data Safety Monitoring Committee are ethical and safety aspects for the patients. The DSMC examines, whether the conduct of the trial is still ethically justifiable, whether security of the patients is ensured, and whether the process of the trial is acceptable. The DSMC will be informed about the adherence to the protocol, the patient recruitment, and the observed serious adverse events. This clinical trial was designed, shall be implemented and reported in accordance with the ICH Harmonized Tripartite Guidelines for Good Clinical Practice, with applicable local regulations (including European Directive 2001/20/EC and with the ethical principles laid down in the Declaration of Helsinki.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
16 Nov 2015
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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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 |
Germany: 4
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Worldwide total number of subjects |
4
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EEA total number of subjects |
4
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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) |
1
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From 65 to 84 years |
3
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85 years and over |
0
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Recruitment
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Recruitment details |
Six patients were enrolled to the trial within 12 months, 4 of them were randomized (3 to placebo/control group, 1 to interventional group) and evaluated in this CSR; two patients were screening failures, one of them due to planned pregnancy. First patient in: 16.11.2015, last patient out: 04.02.2017 | |||||||||
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Pre-assignment
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Screening details |
Patients with relapsing infection and gut colonization with 3GCREB of both genders | |||||||||
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Period 1
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Period 1 title |
Overall (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | |||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Colistin and rifaximin | |||||||||
Arm description |
4 x 2 million units per day colistin and 2 x 400 mg rifaximin | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Colistin
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
4 x 2 million units per day, daily during 3 weeks
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Investigational medicinal product name |
Rifaximin
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Film-coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
2 x 400 mg per day, daily during 3 weeks
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Arm title
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Watch and wait | |||||||||
Arm description |
- | |||||||||
Arm type |
No intervention | |||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Baseline characteristics reporting groups
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Reporting group title |
Colistin and rifaximin
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Reporting group description |
4 x 2 million units per day colistin and 2 x 400 mg rifaximin | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Watch and wait
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Colistin and rifaximin
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Reporting group description |
4 x 2 million units per day colistin and 2 x 400 mg rifaximin | ||
Reporting group title |
Watch and wait
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Reporting group description |
- | ||
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End point title |
3GCREB eradication [1] | |||||||||
End point description |
No evidence for colonization with 3GCREB by rectal swab (preferably; alternatively stool cultures) performed at visit 3 (EOT)
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End point type |
Primary
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End point timeframe |
Visit 3 (EOT)
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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: No formal statistical analysis could be performed due to the small number of patients. |
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| No statistical analyses for this end point | ||||||||||
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End point title |
Early 3GCREB decolonization | |||||||||
End point description |
Early 3GCREB decolonization on days 8-12 after treatment initiation (visit 2)
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End point type |
Secondary
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End point timeframe |
8-12 days after treatment initiation (Visit 2)
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| Notes [2] - antibiotics use for urinary infection |
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| No statistical analyses for this end point | ||||||||||
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End point title |
Late 3GCREB decolonization | |||||||||
End point description |
Late 3GCREB decolonization 9 weeks after EOT (visit 5)
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End point type |
Secondary
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End point timeframe |
9 weeks after EOT (visit 5)
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| Notes [3] - unclear, visit not performed |
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| No statistical analyses for this end point | ||||||||||
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End point title |
Any infection which requires antibiotic therapy | |||||||||
End point description |
Any infection which requires antibiotic therapy until 9 weeks after EOT visit (visit 5)
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End point type |
Secondary
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End point timeframe |
Until 9 weeks after EOT (visit 5)
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| No statistical analyses for this end point | ||||||||||
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End point title |
Infection originating from gastrointestinal tract microflora | |||||||||
End point description |
Infection originating from gastrointestinal tract microflora (including urinary tract infection) which requires antibiotic therapy until 9 weeks after EOT visit (visit 5)
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End point type |
Secondary
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End point timeframe |
Until 9 weeks after EOT visit (visit 5)
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| No statistical analyses for this end point | ||||||||||
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End point title |
Intestinal carriage of colistin- and rifaximin-resistant 3GCREB | |||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
9 weeks after EOT (visit 5)
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| Notes [4] - unclear, visit not performed |
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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 |
Until 9 weeks after EOT visit (visit 5)
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
20
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Reporting groups
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Reporting group title |
Colistin plus rifaximin
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Reporting group description |
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Reporting group title |
Watch and wait
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||
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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? Yes | |||
Date |
Amendment |
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02 Oct 2015 |
The background of the first amendment was the discussion which has arisen after completion of the study protocol, which sample is the optimal starting material for the detection of multidrugresistant
bacteria. Therefore, both materials, rectal swab and stool sample, were included as study material. In the former versions of the protocol, only rectal swab is mentioned. |
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02 Feb 2016 |
The background of the second amendment was to simplify the inclusion and exclusion criteria in order to enhance the recruitment. Therefore inclusion criteria number 3 was edited as follows: a second infection WITHOUT microbiological documentation can be accepted if it can be considered as relapsing infection with the same clinical focus based on clinical judgement and there has been no other relevant pathogen for this episode and the episode required antibiotic treatment considered adequate and clinically effective). |
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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. | |||
| The study has been early terminated by the Sponsor. The main reason for premature study termination was the lower than expected patient recruitment. | |||
