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Controling Intestinal Colonization With Extended Spectrum ß-Lactamase Producing Enterobacteriaceae ESBL-E (CLEAR)

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ClinicalTrials.gov Identifier: NCT01931592
Recruitment Status : Terminated (One of the study drugs was no longer available on a worldwide level.)
First Posted : August 29, 2013
Last Update Posted : May 8, 2017
Sponsor:
Information provided by (Responsible Party):
Maria J.G.T. Vehreschild, University of Cologne

Brief Summary:

Rapid and rational health-care interventions are of great importance to efficiently combat the emergence of resistant and virulent bacteria. In recent years, spread of ESBL-E on a global level has been observed.

For ESBL-E, effective eradication regimens are not yet available. The current study therefore aims to assess a new approach to ESBL-E eradication. To avoid administration of the eradication regimen to patients at low risk of subsequent BSI with ESBL-E, the study population will be restricted to immunocompromised high-risk patients.


Condition or disease Intervention/treatment Phase
Cancer Drug: ESBL eradication regimen Drug: Placebo ESBL eradication Phase 2 Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 29 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Controling Intestinal Colonization of High Risk Patients With Extended Spectrum ß-Lactamase Producing Enterobacteriaceae (ESBL-E) - A Randomized Trial (CLEAR)
Study Start Date : January 2014
Actual Primary Completion Date : October 2016
Actual Study Completion Date : December 2016

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: ESBL eradication regimen
Fosfomycin-trometamol (3 g granules dissolved in 200 ml of water for oral administration every 72h) and colistin (2x106 IU oral solution dissolved in 50-100 ml of water given orally every 6 hours) and gentamicin (an 80 mg oral solution dissolved in 50-100 ml of water given orally every 6 hours) will be administered in a double-blind fashion for a total duration of 7 days (day 1-7). The placebo treatment will be identical in taste, consistency, colour and packaging. To include the oral cavity into the eradication regimen, all medications should be gargled for at least 10 seconds before being swallowed.
Drug: ESBL eradication regimen
Fosfomycin-trometamol (3 g granules dissolved in 200 ml of water for oral administration every 72h) and colistin (2x106 IU oral solution dissolved in 50-100 ml of water given orally every 6 hours) and gentamicin (an 80 mg oral solution dissolved in 50-100 ml of water given orally every 6 hours) will be administered in a double-blind fashion for a total duration of 7 days (day 1-7). The placebo treatment will be identical in taste, consistency, colour and packaging. To include the oral cavity into the eradication regimen, all medications should be gargled for at least 10 seconds before being swallowed.
Other Names:
  • fosfomycin-trometamol 3 g
  • colistin (2x106 IU
  • gentamicin (an 80 mg

Placebo Comparator: Placebo ESBL eradication
Placebo preparations of fosfomycin, gentamicin and colisitin, identical in taste, texture and color will be administered at the same rate as the active comparator medication.
Drug: Placebo ESBL eradication
Placebo preparations of fosfomycin, gentamicin and colisitin, identical in taste, texture and color will be administered at the same rate as the active comparator medication.
Other Name: placebo preparations




Primary Outcome Measures :
  1. Short-term intestinal eradication [ Time Frame: 11 days ]
    Short-term intestinal eradication, defined as a fecal sample , negative for ESBL-E on day 6+/-1 and day 11+/-2


Secondary Outcome Measures :
  1. Long-term intestinal eradication d28 [ Time Frame: 28 days ]
    Long-term intestinal eradication d28, defined as a fecal sample1, negative for ESBL-E on day 28+/-4

  2. Long-term intestinal eradication d42 [ Time Frame: 42 days ]
    Long-term intestinal eradication d42, defined as a fecal sample1, negative for ESBL-E on day 42+/-4

  3. Short-term non-intestinal eradication [ Time Frame: 11 days ]
    Short-term non-intestinal eradication, defined as a combination of ESBL-E negative samples from urine and throat on day 6+/-1 and day 11+/-2

  4. Long-term non-intestinal eradication d28 [ Time Frame: 28 days ]
    Long-term non-intestinal eradication d28, defined as a combination of ESBL-E negative samples from urine and throat on day 28+/-4

  5. Long-term non-intestinal eradication d42 [ Time Frame: 42 days ]
    Long-term non-intestinal eradication d42, defined as a combination of ESBL-E negative samples from urine and throat on day 42+/-4

  6. Emerging presence of non-ESBL multi-drug resistant bacteria [ Time Frame: 42 days ]
    Emerging presence of non-ESBL multi-drug resistant bacteria in the intestine, defined as identification of vancomycin resistant Enterococci (VRE), carbapenem- resistant gram negative rods (4MRGN according to the KRINKO definition) or colistin-resistant enterobacteria (except Proteus and Serratia spp.) in a fecal sample on day 6+/-1, day 11+/-2, day 28+/-4 or day 42+/-4

  7. Intestinal microbiome [ Time Frame: 42 days ]
    Association between the intestinal microbiome pattern and the outcome of eradication on baseline, day 6+/-1, day 11+/-2, day 28+/-4 or day 42+/-4

  8. Quantitative assessment of intestinal ESBL-E burden [ Time Frame: 42 days ]
    Quantitative assessment of intestinal ESBL-E burden on baseline, day 6+/-1, day 11+/-2, day 28+/-4 or day 42+/-4

  9. Incidence and severity of AEs [ Time Frame: 42 days ]
    Incidence and severity of AEs

  10. Rate of AE-related study drug discontinuations [ Time Frame: 42 days ]
    Rate of AE-related study drug discontinuations



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Fecal colonization with ESBL-E, as confirmed by a positive sample (rectal swab or stool sample) obtained within 14 days prior to study enrolment
  • Ongoing or scheduled immunosuppression:

    • allogeneic or autologous hematopoietic stem cell transplantation within 14 days after enrollment or
    • chemotherapy with an expected duration of chemotherapy-associated neutropenia of at least 7 days within 14 days after enrollment or
    • solid organ transplantation within 14 days after enrollment or
    • administration of high-dose corticosteroids or other immunosuppressants for acute rejection of a solid organ transplant or for graft versus host disease after stem cell transplantation
  • Age of at least 18 years
  • Subject is not legally incapacitated
  • Written informed consent from the trial subject has been obtained

Exclusion Criteria:

  • Current or scheduled administration of ESBL-E active antibiotic treatment after receipt of the most recent sample showing intestinal ESBL-E colonization and within 10 days after randomization
  • Planned selective digestive tract decolonization within 42 days following randomization
  • Known hypersensitivity or allergy to any of the components of the study treatment
  • Moderate or severe liver dysfunction at baseline, defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels greater than three times the upper limit of normal (ULN), AND a total bilirubin level greater than two times the ULN
  • Serum creatinine > 2 x the upper limit of the ULN
  • Inability to take oral medication
  • Concurrent participation in another clinical trial with an investigational drug is not permitted, unless the drug under study is related to the treatment of the underlying condition or a transplantation
  • Current pregnancy or nursing period
  • In female study participants, failure to use highly-effective contraceptive methods. The following contraceptive methods with a Pearl Index lower than 1% are regarded as highly-effective:

    • Oral hormonal contraception ('pill')
    • Dermal hormonal contraception
    • Vaginal hormonal contraception (NuvaRing®)
    • Contraceptive plaster
    • Long-acting injectable contraceptives
    • Implants that release progesterone (Implanon®)
    • Tubal ligation (female sterilization)
    • Intrauterine devices that release hormones (hormone spiral)
    • Double barrier methods This means that the following are not regarded as safe: condom plus spermicide, simple barrier methods (vaginal pessaries, condom, female condoms), copper spirals, the rhythm method, basal temperature method, and the withdrawal method (coitus interruptus).
  • Patient has any other condition that, in the opinion of the investigator, would jeopardize the safety or rights of the patient participating in the study, would make it unlikely for the patient to complete the study, or would confound the results of the study
  • Persons with any kind of dependency on the investigator or employed by the sponsor or investigator
  • Persons held in an institution by legal or official order

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01931592


Locations
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Germany
University hospital Hamburg Eppendorf
Hamburg, HH, Germany, 20149
University Hospital Cologne
Cologne, NRW, Germany, 50931
Sponsors and Collaborators
Maria J.G.T. Vehreschild
Investigators
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Principal Investigator: Maria J Vehreschild, MD University Hospital Cologne
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Maria J.G.T. Vehreschild, Dr. med., University of Cologne
ClinicalTrials.gov Identifier: NCT01931592    
Other Study ID Numbers: Uni-Koeln-1667
First Posted: August 29, 2013    Key Record Dates
Last Update Posted: May 8, 2017
Last Verified: May 2017
Keywords provided by Maria J.G.T. Vehreschild, University of Cologne:
ESBL
neutropenia
eradication
bloodstream infection
immunosuppression
Additional relevant MeSH terms:
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Gentamicins
Colistin
Fosfomycin
Anti-Bacterial Agents
Anti-Infective Agents
Protein Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action