Carriage of 3GCREB in patients at risk for relapsing infection: randomizedcontrolled trial of intestinal decolonization with colistin plus rifaximi

Phase 2

• Conditions: A04.9; Bacterial intestinal infection, unspecified

• Registration Number: DRKS00006330
• Lead Sponsor: niversitätsklinikum Freiburg

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2015-05-18
• Last Update Posted: 19 August 2024

Recruitment & Eligibility

• Status: Recruiting stopped after recruiting started
• Sex: All
• Target Recruitment: 3

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. Specific inclusion criteria for patients with a history of recurrent urinary tract infections: Result of a current urine culture (done 3 weeks before day 0 of the study) has to be on hand. 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

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 within the last 30
days before the start of this trial (except for registry and diagnostic trials);
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.

Study & Design

• Study Type: interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
3GCREB eradication defined as: no evidence for colonization with 3GCREB by preferably rectal swab and/or stool cultures performed at end of treatment visit (=visit 3) and at 1-2 weeks after end of treatment visit (=visit 4).

Secondary Outcome Measures

Name	Time	Method
- early (rapid) 3GCREB decolonization (days 8-12 after treatment initiation=visit 2); <br>- late (sustained) 3GCREB decolonization (week 9 after end of treatment visit =visit 5); <br>- any infection which requires antibiotic therapy<br>- infection originating from gastrointestinal tract microflora (including urinary tract infection) which requires antibiotic therapy; <br>- intestinal carriage of colistin- and rifaximin-resistant 3GCREB;