E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Immunocompromised patients at high risk of bloodstream infections with colonizing bacteria. |
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E.1.1.1 | Medical condition in easily understood language |
Patients with an compromised immune system and an increased risk of contracting infections in their bloodstream due to bacteria colonizing their gut. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Bacterial Infections and Mycoses [C01] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10066481 |
E.1.2 | Term | Hematological malignancy |
E.1.2 | System Organ Class | 100000004864 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10067862 |
E.1.2 | Term | Allogeneic stem cell transplantation |
E.1.2 | System Organ Class | 100000004865 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10054990 |
E.1.2 | Term | Immunodeficiency secondary to organ transplantation |
E.1.2 | System Organ Class | 100000004870 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10021458 |
E.1.2 | Term | Immunodeficiency secondary to transplantation chemotherapy |
E.1.2 | System Organ Class | 100000004870 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10021452 |
E.1.2 | Term | Immunodeficiency secondary to chemotherapy (excl corticosteroids) |
E.1.2 | System Organ Class | 100000004870 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Assessment of efficacy and safety of an antimicrobial regimen in the short-term and long-term eradication of ESBL-E from the intestinal flora of immunocompromised high-risk patients. |
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E.2.2 | Secondary objectives of the trial |
See secondary endpoints (section E 5.2) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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: o allogeneic or autologous hematopoietic stem cell transplantation within 14 days after enrolment or o chemotherapy with an expected duration of chemotherapy-associated neutropenia of at least 7 days within 14 days after enrolment or o solid organ transplantation within 14 days after enrolment or o 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
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E.4 | Principal exclusion criteria |
• Current or scheduled administraton of ESBL-E active antibiotic treatment or prophylaxis after receipt of the most recent sample showing intestinal ESBL-E colonization and within 10 days after randomization • Planned selective digestive tract decolonization (SDD) 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 ULN • Current pregnancy or nursing period • Failure to use highly-effective contraceptive methods • 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, transplantation or immunosuppression
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E.5 End points |
E.5.1 | Primary end point(s) |
• Short-term intestinal eradication, defined as a fecal sample, negative for ESBL-E on day 6+/-1 and day 11+/-2 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
on day 6+/-1 and day 11+/-2 |
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E.5.2 | Secondary end point(s) |
• 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 d28, defined as a combination of ESBL-E negative samples from skin, urine and the throat on day 28+/-4 • Long-term non-intestinal eradication d42, defined as a combination of ESBL-E negative samples from skin, urine and the throat on day 42+/-4 • Short-term overall eradication, defined as a combination of ESBL-E negative samples from feces, skin, urine and the throat on day 6+/-1 and day 11+/-2 • Long-term overall eradication d28, defined as a combination of ESBL-E negative samples from feces, skin, urine and the throat on day 28+/-4 • Long-term overall eradication d42, defined as a combination of ESBL-E negative samples from feces, skin, urine and the throat on day 42+/-4 • Emerging presence of non-ESBL multi-drug resistant bacteria in the intestine, defined as identification of vancomycin resistant Enterococci (VRE), 4 multi-drug-resistant gram negative rods (MRGN) according to the KRINKO definition or colistin-resistant bacteria in a fecal sample on day 6+/-1, day 11+/-2, day 28+/-4 or day 42+/-4 • 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 • Quantitative assessment of intestinal ESBL-E burden on baseline, day 6+/-1, day 11+/-2, day 28+/-4 or day 42+/-4 • Incidence and severity of AEs • Rate of AE-related study drug discontinuations
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
day 6+/-1, day 11+/-2, day 28+/-4 or day 42+/-4 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Premature termination of the trial will be considered if: • The risk-benefit balance for the trial subject changes markedly • It is no longer ethical to continue treatment with the IMP • The sponsor considers that the trial must be discontinued for safety reasons • An interim analysis or results of other research show that one of the trial treatments is superior or inferior to another • It is no longer practicable to complete the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | 0 |