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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
450
Already incl. in arm description
Already incl. in arm description
Already incl. in arm description
Hvidovre Hospital
Hvidovre, Denmark
RECRUITINGKøge sygehus
Køge, Denmark
RECRUITINGClinical cure of recurrent Clostridium difficile infection defined as patient-reported abscence of Clostridium difficile infection 90 days after treatment.
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.
Time frame: 90 days
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).
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.
Time frame: 30 and 180 days after ended treatment
Days with diarrhea
Time frame: 1, 4, 8 and 12 days after ended treatment
CDI-associated hospital admission and hospital admission of other causes in the follow-up period
Time frame: 180 days after ended treatment
CDI-associated hospital outpatient contact and hospital outpatient contact of other causes in the follow-up period
Time frame: 180 days after ended treatment
CDI-associated mortality and all-cause mortality
Time frame: 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.
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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.
Time frame: 90 days after ended treatment
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.
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.
Time frame: 90 days after ended treatment
Effect of the treatment depending on the patients serum-level of antibodies towards toxin A and B at the time of inclusion.
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.
Time frame: 90 days after ended treatment
Side effects in the three treatment arms
Time frame: 14 days after ended treatment
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.
Performed in a subgroup of patients.
Time frame: 180 days after ended treatment
Other antibiotic treatments associated with new recurrences of CDI
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.
Time frame: Within 180 days after ended treatment
Evaluation of the composition of bile acids before and after treatment with FMT/RBT.
Analyzed in conjunction with the microbiota composition and the treatment effect. Performed in a subgroup of patients.
Time frame: 90 days after ended treatment
Characterisation of the CD strains by whole genome sequencing
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.
Time frame: 90 days after ended treatment
Identification of age as a risk factor for treatment success/failure
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.
Time frame: 90 days after ended treatment
Identifying if Charlson comorbidity index is associated to treatment success/failure.
At inclusion the patient's Charlson Comorbidity index will be calculated and put in the patient's record unique to this trial.
Time frame: 90 days after ended treatment