randomized controlled trial of intestinal decolonization with colistin plus rifaximin.

Phase 1

Conditions: Intestinal carriage of 3GCREB responsible for relapsing infection
Therapeutic area: Diseases [C] - Bacterial Infections and Mycoses [C01]

Registration Number: EUCTR2014-000180-41-DE

Lead Sponsor: Medical Center - University of Freiburg

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: Not specified

Inclusion Criteria

1. Written informed consent obtained according to international guidelines and local laws
2. Male or female patients aged 18 or older
3. Patients with at least two episodes of infection
- during the last 12 months,
- each time requiring specific antibiotic therapy and
- due to the same species of 3GCREB (ESBL and/or AmpC enterobacteria) but not necessarily with identical susceptibility test results.
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
4. Patients with current colonization with the same species of 3GCREB as in (3)
- on two occasions within three weeks before day 0 of the study (i.e. day -21 to -1).
- proven by two cultures taken at least one week apart from each other, with the second culture taken within one week before day 0 of the study (i.e. day -7 to -1)
- with the first culture taken from any site (e.g. sputum, wound, urinary tract, rectal swab, stool) *
- and the second being a rectal swab, alternatively stool) **
- absence of antibiotic therapy, except
- if treatment stop is planned before day 0 of the trial
- short-term therapy for uncomplicated urinary tract infection (oral fosfomycin, norfloxacin, trimethoprim or trimethoprim-sulfamethoxazole for 3 days or less, or nitrofurantoin for no more than 5 days)
5. Known status concerning urinary tract colonisation before day 0 of the study. Result of urine culture which was routinely performed during medical care of a patient will be accepted.
6. Ability to understand the nature of the trial and the trial related procedures and to comply with them.

* Result of culture which was routinely performed during medical care of a patient will be accepted
** To obtain at least one baseline culture sample for analysis in the Microbiology Reference Center (see section
7.6.11), results of cultures routinely performed cannot be accepted
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 154
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20

Exclusion Criteria

1. Patients with rapidly fatal underlying disease (i.e. McCabe category 3)
2. Patients with severe diarrhea (defined as >5 bowel movements per day with loose stools) in the last three days
3. Patients with severe nausea/vomiting
4. Patients with inability to swallow
5. Patients who received recent (last 3 weeks) treatment with oral colistin and/or rifaximin
6. Patients with expected low compliance with drug regimen
7. Simultaneous participation in other interventional trials which could interfere with this trial and/or participation before the end of a required restriction period;
8. Patients with contraindications to the study drugs such as known intolerance of the study drugs (including other rifamycin derivatives like rifampin/rifampicin, rifabutin and rifapentine)
9. Co-medication with ibrutinib (recently approved tyrosine kinase inhibitor for treatment of patients with B cell lymphomas)
10. Known or persistent abuse of medication, drugs or alcohol
11. Persons who are in a relationship of dependence/employment with the sponsor or the investigator.

Specific exclusion criteria for female patients:
1. Current or planned pregnancy, nursing period;
2. Failure to use one of the following safe methods of contraception: female condoms, diaphragm or coil, each used in combination with spermicides; intra-uterine device; hormonal contraception in combination with a mechanical method of contraception