CLEAR

Assessment of the efficacy of an antimicrobial regimen in the short-term and long-term eradication of ESBL-E from the intestinal flora of haematological high-risk patients.

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

• Long-term intestinal eradication d28, defined as a fecal sample, negative for ESBL-E on day 28+/-4

•  Long-term intestinal eradication d42, defined as a fecal sample, negative for ESBL-E on day 42+/-4

•  Short-term non-intestinal eradication, defined as a combination of ESBL-E negative samples from skin, urine and the throat on day 6+/-1 and day 11+/-2

• Long-term non-intestinal eradication d30, defined as a combination of ESBL-E negative samples from skin, urine and the throat on day 28+/-4

• Long-term non-intestinal eradication d60, defined as a combination of ESBL-E negative samples from skin, urine and the throat on day 42+/-4

[...]

• Fecal colonization with ESBL-E coli or ESBL-K.pneumoniae, as confirmed by a positive sample (rectal swab or stool sample) obtained within 14 days prior to study enrolment
• Scheduled  allogeneic or autologous hematopoietic stem cell transplantation or
• chemotherapy with an expected duration of chemotherapy-associated neutropenia (<500 neutrophils/mL or white blood count <1,000 leukocytes/mL) of at least 7 days within 14 days after enrolment
• solid organ transplantation within 14 days after enrolment 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 or for a rheumatologic disease or
• expected neutropenia (<500 neutrophils/mL or white blood count <1,000 leukocytes/mL) of at least 7 days due to an underlying condition, including functional neutropenia (<500 functional neutrophils/mL or functional white blood count <1,000 leukocytes/mL)
• Age of at least 18 years
• Subject is not legally incapacitated
• Written informed consent from the trial subject has been obtained

• Current or scheduled administraton of ESBL-E active antibiotic treatment¹ 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 AST or 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 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
• [...]

Fosfomycin (3 g granules for oral administration every 72h) and colistin (2x106 IU in granules, given orally every 6 hours) and gentamicin (an 80 mg oral solution 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.