Clostridium difficile associated diarrhoea (CDAD)
Conditions
Interventions
Trade Name: Mutaflor® Suspension
Pharmaceutical Form: Oral suspension
INN or Proposed INN: ESCHERICHIA COLI STRAIN NISSLE 1917
Other descriptive name: ESCHERICHIA COLI STRAIN NISSLE 1917
Concentration
Sponsors
Ardeypharm GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: o Signed informed consent form by the patient o C. difficile associated diarrhoea (illnesses of mild to moderate severity) o Age = 18 years with life expectancy of 3 months or more o Positive detection of C. difficile protein GDH and toxin A and / or B and diarrhoea (definition: = 3 liquid or watery stools per day or = 8 in 48 h) Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 18 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 90
Exclusion criteria
Exclusion criteria: o Non-fulfilment of at least one inclusion criterion o Participation in an interventional clinical trial according to the German medicines act (AMG) within the last 30 days or simultaneously o Expectable lack of cooperation/compliance o Women of childbearing potential without conceptual protection o Pregnancy and breast feeding period o Abuse of alcohol (daily intake of 20 g of pure alcohol in women and 30 g of pure alcohol in men), medications or drugs o Limited legal capacity o Housing in an institution as a result of official or court orders o Dependency of a person on sponsor, trial site or investigator o Incompatibility with study medication o Necessity of intake of other antidiarrhoeals, especially antimotility agents o Other reasons that, in the opinion of the examiner, speak against inclusion of the patient to the trial o The presence of more than 2 of the following predictors of increased risk of a severe CDAD progression: ? Fever > 38.5 °C ? Leucocytosis > 15 × 10^9/L ? Left shift > 20% rod meaty granulocytes ? Hypoalbuminemia 50% of initial value ? Lactate boost = 5mmol/l ? Age > 75 years ? Significant morbidity (e.g. renal failure, immune suppression, etc.) o Severe form of the CDAD/ C. difficile infection (CDI): Severe CDAD/CDI is defined as an episode of CDAD/CDI with (one or more specific signs and symptoms of) severe colitis or a complicated course of disease, with significant systemic toxin effects and shock, resulting in need for intensive care unit (ICU) admission, colectomy or death o Enterocolitis that is not associated with C. difficile infection, such as active Crohn's disease*, active ulcerative colitis*, colitis caused by radiation or other pathogen-induced colitis o Positive TPER-Test (test will only be performed on patients with community acquired CDAD) o Other serious comorbidities, which, in the opinion of the investigator, call into question the protocol-compliant implementation of the study. This applies in particular to comorbidities, which could worsen if there is an aggravation of the CDAD. o Non-deductibility of a current antibiotic treatment of a disease other than the CDAD. o Intake of more than three 400 mg-doses of metronidazole (daily dose) or longer than 24 hours of metronidazole therapy to treat the acute CDAD episode before enrolment into the study. o Intake of more than four 125 mg-doses of vancomycin (daily dose) or longer than 24 hours of vancomycin therapy to treat the acute CDAD episode before enrolment into the study. o Taking more than three doses or longer than 24 hours of a probiotic drug to treat the acute CDAD episode before enrolment into the study. * Patients in remission are not excluded from the study!
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Main objective of this study is to show that the administration of E. coli strain Nissle 1917 (EcN) results in a non-inferior CDAD healing rate compared to vancomycin treatment.;Secondary Objective: oShowing that the administration of EcN results in a non-inferior CDAD relapse rate compared to vancomycin treatment oShowing that the administration of EcN results in a non-inferior CDAD healing rate without recurrence 30 days after treatment compared to vancomycin treatment oShowing that the administration of EcN results in a non-inferior CDAD healing rate without recurrence 90 days after treatment compared to vancomycin treatment oAnalyses of the development of patients´ inflammatory markers oAssessment of safety and tolerability of the study medication oPresentation of the course of diarrhoea symptoms during the therapy phase oPresentation of the course of the abdominal pain related to CDAD during the therapy phase ;Primary end point(s): Primary end point of this study is the CDAD healing rate after 14 days of treatment. Healing is defined as: o< 3 liquid/mushy or watery stools per day AND oAssessment of abdominal pain related to CDAD is 0 or 1 AND oAssessment of the investigator, that the patient does not need further therapy to treat CDAD Classification: oAssessment of abdominal pain (strongest pain episode of the day related to CDAD) by the patient: None=0 ; Mild=1 ; Moderate= 2 ; Severe= 3 ;Timepoint(s) of evaluation of this end point: after 14 days of treatment with IMP | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): o Rate of CDAD relapse for different treatment groups o Rate of CDAD healing and CDAD recurrence rate within 30 or 90 days after treatment, respectively o Values of different inflammatory markers o Reports of adverse events (AEs) and adverse drug reactions (ADRs) o The entries of the patients in the diary regarding defecation frequency and consistency of the faeces o The entries of the patients in the diary regarding abdominal pain related to CDAD ;Timepoint(s) of evaluation of this end point: o Rate of CDAD relapse for different treatment groups: within/after an observation period of not longer than 13 weeks after treatment period o Rate of CDAD healing and CDAD recurrence rate within 30 or 90 days after treatment, respectively: after treatment period and 30 or 90 days after treatment, respectively o Values of different inflammatory markers: over the entire course of the supject participation o Reports of adverse events (AEs) and adverse drug reactions (ADRs): over the entire course of the subject participation o The entries of the patients in the diary regarding defecation frequency and consistency of the faeces: after 14 days of treatment with IMP o The entries of the patients in the diary regarding abdominal pain related to CDAD: after 14 days of treatment with IMP | — |
Countries
Germany
Contacts
Public ContactClinical research
Ardeypharm GmbH
Outcome results
None listed