Clostridium Difficile
Conditions
Keywords
Recurrence, Infection
Brief summary
The purpose of the study is to investigate if treatment with fecal microbiota transplantation or rectal bacteriotherapy is superior to standard vancomycin in patients with recurrent Clostridium Difficile infections.
Detailed description
Clostridium difficile infection (CDI) is the most common nosocomial infection in the western world. CDI is associated with high morbidity and mortality and is a great burden for the health care system leading Center of Disease Control and Prevention (CDC) to identify it as one of three most important/urgent threats to public health. Despite antimicrobial treatment of CDI, 20% of the patients have recurrence of CDI. Due to a dysbiosis in the gut microbiota the antimicrobial treatment seems to be less effective. Fecal microbiota transplantation (FMT) is an alternative treatment for recurrent CDI. Studies have shown a cure rate up to 90% in patients with recurrent CDI. One alternative to FMT is rectal bacteriotherapy (RBT) which is a standardized bacterial culture made in the laboratory consisting of 12 different bacteria. RBT has never been investigated in a clinical trial. The project is a randomized controlled trial including 450 patients with recurrent CDI will be, after accepting participation, allocated to receive vancomycin alone or vancomycin followed by either FMT or RBT. The patients will be followed up for 180 days. Cure is defined as resolution of CDI symptoms 90 days after treatment.
Interventions
DRUGVancomycin
Already incl. in arm description
DRUGFecal microbiota transplantation
Already incl. in arm description
DRUGRectal bacteriotherapy
Already incl. in arm description
Sponsors
Hvidovre University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years * Verified recurrent CDI with symptoms of CDI and microbiological verification (PCR). * Previously treated for CDI with at least 10 days of vancomycin or metronidazole. * Be able to read and understand Danish.
Exclusion criteria
* Life expectancy \< 3 months. * Allergy toward vancomycin * Other infection in the GI tract with clinical symptoms similar to CDI. * Other illness in the GI tract with clinical symptoms similar to CDI. * Use of antibiotics for more than 14 days treating other infections * Planning pregnancy, pregnancy or breast feeding. * Severe immune suppression which makes FMT/RBT relatively contraindicated
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical cure of recurrent Clostridium difficile infection defined as patient-reported abscence of Clostridium difficile infection 90 days after treatment. | 90 days | Clinical cure defined as patient-reported abscence of Clostridium difficile infection 90 days after treatment. The investigator will call the patient by telephone and fill out af digital questionnaire. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Days with diarrhea | 1, 4, 8 and 12 days after ended treatment | — |
| CDI-associated hospital admission and hospital admission of other causes in the follow-up period | 180 days after ended treatment | — |
| CDI-associated hospital outpatient contact and hospital outpatient contact of other causes in the follow-up period | 180 days after ended treatment | — |
| CDI-associated mortality and all-cause mortality | 30, 90 and 180 days after ended treatment | — |
| Compare numbers of patients with clinical cure after study treatment divided into two groups depending on numbers of recurrences of CDI. | 90 days after ended treatment | Clinical cure is defined as patient-reported abscence of Clostridium difficile infection 90 days after treatment. The investigator will call the patient by telephone and fill out a digital questionnaire. Number of patients with clinical cure of recurrent Clostridium difficile infection will be divided into two groups according to numbers of recurrences of CDI; * Group 1; patients with one recurrence * Group 2; patients with 2 or more recurrences. The division will be done based on patient records and the questionnaire. The information will be aggregated in the digital journal unique to this trial. The numbers of patients with clinical cure in the two groups will be compared to see if one group response better to study treatment than the other. |
| Effect of the treatment depending on the CD strain - i.e. toxin B CDI cases, toxin B plus binary toxin CDI cases and CD027 CDI cases. | 90 days after ended treatment | The investigator will call the patient by telephone and fill out af digital questionnaire. The lab result will give the investigator information about which strain the patient was infected with and this will be aggregated in the digital patient journal. |
| Effect of the treatment depending on the patients serum-level of antibodies towards toxin A and B at the time of inclusion. | 90 days after ended treatment | At inclusion the investigator will collect a blood sample to analysis for toxin A and B antibodies. The lab result will be aggregated in the digital patient journal. |
| Early or late recurrence of CDI after the end of treatment defined as recurrence of symptoms of CDI and a positive stool sample with Clostridium difficile (PCR). | 30 and 180 days after ended treatment | Patient with recurrence of CDI in the follow up period will be categorized as an early recurrence if the recurrence is in the first 30 days after treatment and as a late recurrence if the recurrence is after 180 days after treatment. The investigator will call the patient by telephone and fill out af digital questionnaire and thereafter categorize the patient. |
| Characterisation of the gut microbiota before and after treatment with FMT/RBT in conjunction with characterisation of the donor's microbiota or the RBT bacterial mix. | 180 days after ended treatment | Performed in a subgroup of patients. |
| Other antibiotic treatments associated with new recurrences of CDI | Within 180 days after ended treatment | The investigator will call the patient by telephone and fill out af digital questionnaire. Furthermore the investigator has access to a database with all prescription drugs incl. antibiotics. These informations will be collected and aggregated in the digital patient journal unique for this study. |
| Evaluation of the composition of bile acids before and after treatment with FMT/RBT. | 90 days after ended treatment | Analyzed in conjunction with the microbiota composition and the treatment effect. Performed in a subgroup of patients. |
| Characterisation of the CD strains by whole genome sequencing | 90 days after ended treatment | Characterisation of the CD strains involved to determine if a potential recurrence is a true recurrence or a reinfection with another strain. Whole genome sequencing will be performed by the department of Clinical Microbiology in Hvidovre Hospital. This information will be collected by the investigator and aggregated in the digital patient journal unique for this trial. |
| Identification of age as a risk factor for treatment success/failure | 90 days after ended treatment | The investigator will call the patient by telephone for information about abscence of CDI and fill out af digital questionnaire. This information and the patient's age will be aggregated in the digital patient journal. |
| Identifying if Charlson comorbidity index is associated to treatment success/failure. | 90 days after ended treatment | At inclusion the patient's Charlson Comorbidity index will be calculated and put in the patient's record unique to this trial. |
| Side effects in the three treatment arms | 14 days after ended treatment | — |
Countries
Denmark
Contacts
Primary ContactAndreas M Petersen, MD, PhD
Outcome results
None listed