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

NCT01931592 | Terminated Phase 2

• 1 other identifier: Uni-Koeln-1667
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 2

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.

Conditions

Cancer

Keywords

ESBL; neutropenia; eradication; bloodstream infection; immunosuppression

Outcome Measures

Primary Outcomes (1)

• Short-term intestinal eradication

  Short-term intestinal eradication, defined as a fecal sample , negative for ESBL-E on day 6+/-1 and day 11+/-2

  11 days

Secondary Outcomes (10)

• Long-term intestinal eradication d28

  28 days

• Long-term intestinal eradication d42

  42 days

• Short-term non-intestinal eradication

  11 days

• Long-term non-intestinal eradication d28

  28 days

• Long-term non-intestinal eradication d42

  42 days

Study Arms (2)

ESBL eradication regimen

ACTIVE COMPARATOR

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

Placebo ESBL eradication

PLACEBO COMPARATOR

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

Interventions

ESBL eradication regimen DRUG

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.

Also known as: fosfomycin-trometamol 3 g, colistin (2x106 IU, gentamicin (an 80 mg

ESBL eradication regimen

Placebo ESBL eradication DRUG

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.

Also known as: placebo preparations

Placebo ESBL eradication

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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®)

Sponsors & Collaborators

• Maria J.G.T. Vehreschild: lead

Study Sites (2)

University hospital Hamburg Eppendorf

Hamburg, Hamburg, 20149, Germany

Location

University Hospital Cologne

Cologne, North Rhine-Westphalia, 50931, Germany

Location

Related Publications (1)

• Dimitriou V, Biehl LM, Hamprecht A, Vogel W, Dorfel D, Peter S, Schafhausen P, Rohde H, von Lilienfeld-Toal M, Klassert TE, Slickers P, Ehricht R, Slevogt H, Christ H, Hellmich M, Farowski F, Tsakmaklis A, Higgins PG, Seifert H, Vehreschild MJGT. Controlling intestinal colonization of high-risk haematology patients with ESBL-producing Enterobacteriaceae: a randomized, placebo-controlled, multicentre, Phase II trial (CLEAR). J Antimicrob Chemother. 2019 Jul 1;74(7):2065-2074. doi: 10.1093/jac/dkz124.

  PMID: 31220256 DERIVED

MeSH Terms

Conditions

Neoplasms; Neutropenia; Sepsis

Interventions

Colistin; Gentamicins

Condition Hierarchy (Ancestors)

Agranulocytosis; Leukopenia; Cytopenia; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukocyte Disorders; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Polymyxins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Lipopeptides; Lipids; Antimicrobial Cationic Peptides; Peptides; Amino Acids, Peptides, and Proteins; Antimicrobial Peptides; Pore Forming Cytotoxic Proteins; Membrane Proteins; Proteins; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Maria J Vehreschild, MD

  University Hospital Cologne

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Dr. med.

Study Record Dates

• First Submitted: August 26, 2013
• First Posted: August 29, 2013
• Study Start: January 1, 2014
• Primary Completion: October 1, 2016
• Study Completion: December 1, 2016
• Last Updated: May 8, 2017

Record last verified: 2017-05

Locations

DE (2)