recurrent C. difficile infection MedDRA version: 20.0 Level: PT Classification code 10009657 Term: Clostridium difficile colitis System Organ Class: 10021881 - Infections and infestations MedDRA version: 20.0 Level: LLT Classification code 10012748 Term: Diarrhoea, Clostridium difficile System Organ Class: 10021881 - Infections and infestations MedDRA version: 20.0 Level: LLT Classification code 10012734 Term: Diarrhea, Clostridium difficile System Organ Class: 10021881 - Infections and infes
Conditions
Interventions
Trade Name: Zinplava
Pharmaceutical Form: Concentrate for solution for infusion
Sponsors
Leiden University Medical Center
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - 18-90 years old - diarrhea (3 or more unformed stools per 24h for two consecutive days; or >= 8 unformed stools per 48h) - positive PCR test for toxin A/B genes and/or positive toxin EIA for current and previous episodes (low PCR cycle threshold value when only PCR performed) - a minimum of two prior CDI episodes - previous episode is maximum of 3 months prior to the current episode - the current episode responds well to Standard of Care treatment (vancomycin or fidaxomicin orally). - Assessment of the severity of the disease will be performed according to the ESCMID recommendations. - Both mild and severe CDI will be included 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 66 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 66
Exclusion criteria
Exclusion criteria: - Severe complicated CDI, i.e presence of: hypotension, septic shock, elevated serum lactate, ileus, toxic megacolon, bowel perforation, or any fulminant course of disease. - ICU admission for underlying disease - pregnancy or current desire for pregnancy - breastfeeding - (prolonged) use of antibiotics (other than for treatment of CDI) during the study period or directly after the intervention - previous use of bezlotoxumab or fecal microbiota transplantation - a history of underlying congestive heart failure (potential safety signal phase-III trail bezlotoxumab). - Diagnosis of inflammatory bowel disease in medical history.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate whether a treatment strategy offering bezlotoxumab before FMT in patients suffering from multiple recurrent CDI results in equal efficacy compared with a treatment strategy with initial FMT. Strategy A includes bezlotoxumab as ancillary treatment as first option, and FMT in case of failure. Option B includes FMT as ancillary treatment as first option, and antibiotic treatment with fidaxomicin in case of failure.;Secondary Objective: To provide: A. a point estimate of CDI recurrence (i.e. relapse within 12 weeks after initial cure,), after standard CDI ABx plus either bezlotoxumab or FMT (as initial treatment). To determine B. the initial cure rate of standard CDI ABx plus either bezlotoxumab or FMT (as initial treatment) C. the sustained cure rate, i.e. cure without relapse within 12 weeks, of standard CDI ABx plus either bezlotoxumab or FMT (as initial treatment). D. adverse events E. development of post-treatment irritable bowel syndrome like symptoms associated with bezlotoxumab treatment or FMT treatment F. duration of hospitalization G. use of antibiotics H. eradication of toxicogenic C. difficile after treatment I. changes in gut microbiota profiles pre- and post-treatment J. patient well-being before and after treatment;Primary end point(s): Global cure of the treatment strategy. Global cure is defined as cure without relapse of CDI within 12 weeks after completion of the treatment strategy in the study arm, i.e. after completion of secondary treatment in case of failure on initial treatment. ;Timepoint(s) of evaluation of this end point: 12 weeks after completion of the treatment strategy. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Initial cure after treatment with bezlotoxumab or FMT. Defined as cure after completion of the primary CDI treatment in the study arm. Initial cure is assessed at day 2 after end of treatment. - Recurrence after initial treatment with bezlotoxumab or FMT. Defined as CDI relapse within 12 weeks, after initial cure. - Sustained cure after initial treatment with bezlotoxumab or FMT. Defined as cure without CDI relapse within 12 weeks. - Adverse events. Throughout the entire study all adverse events will be noted. After the final study procedure of the last patient, all adverse events will be categorized: 1. Most likely related to ancillary CDI treatment (bezlotoxumab or FMT) 2. May be related to ancillary CDI treatment 3. Not related to ancillary CDI treatment - Development of post-treatment irritable bowel syndrome like symptoms associated with bezlotoxumab treatment or FMT treatment after treatment during 12 weeks of follow-up - Duration of hospitalization - (Rate of) use of antibiotics after treatment during 12 weeks of follow-up - Eradication of toxigenic C. difficile 3 weeks and 12 weeks after end of treatment assessed by PCR - Fecal microbiota profile pre-treatment and 3 weeks and 12 weeks after end of treatment assessed by 16S rRNA amplicon sequencing. - Costs per cured patient (global and sustained cure) and costs per QALY gained using the EQ-5D-5L health questionnaire The following data will also be collected: - Patients’ characteristics, i.e. age, medical history, comorbidities, comedication - Presence of risk factors for severe and recurrent CDI - Patient wellbeing as assessed by questionnaire - Defecation pattern during treatment and follow-up;Timepoint(s) of evaluation of this end point: - 12 weeks follow-up - Initial cure is assessed at day 2 after end of treatment. - Global cure is assessed 12 weeks after completion of the treatment strategy in the study arm - Eradication of toxigenic C. difficile 3 weeks and 12 | — |
Countries
Netherlands
Contacts
Public ContactDepartment of Medical Microbiology
Leiden University Medical Center
Outcome results
None listed