Rectal Bacteriotherapy, Fecal Microbiota Transplantation or Oral Vancomycin Treatment of Recurrent Clostridium Difficile Infections

Hvidovre University Hospital

Status and phase: Unknown; Phase 3

Conditions: Clostridium Difficile

Treatments: Drug: Vancomycin; Drug: Fecal microbiota transplantation; Drug: Rectal bacteriotherapy

Study type: Interventional

Funder types: Other

Identifiers

NCT02774382

SJ-478

Details and patient eligibility

About

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.

Full 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.

Enrollment: 450 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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450 participants in 3 patient groups

Vancomycin

Active Comparator group

Description:

Oral vancomycin according to number of recurrences (Danish guidelines): First recurrence: Capsule vancomycin 125 mg x 4 p.o. times daily for 14 days ≥2 recurrences: * capsule vancomycin 125 mg x 4 times daily p.o. for 14 days followed by * capsule vancomycin 125 mg x 2 times daily p.o. for 7 days followed by * capsule vancomycin 125 mg x 1 times daily p.o. for 7 days followed by * capsule vancomycin 125 mg x 1 p.o. every second day for 7 days followed by * capsule vancomycin 125 mg x 1 p.o. every third day for 14 days

Treatment:

Drug: Vancomycin

Vancomycin + fecal microbiota transplantation

Experimental group

Description:

Capsule vancomycin 125 mg x 4 times daily p.o. for 7-14 days followed by Fecal Microbiota Transplantation with 200 ml fecal suspension administrated with a rectal catheter.

Treatment:

Drug: Vancomycin

Drug: Fecal microbiota transplantation

Vancomycin + rectal bacteriotherapy

Experimental group

Description:

Capsule vancomycin 125 mg x 4 times daily p.o. for 7-14 days followed by Rectal bacteriotherapy with 200 ml suspension of a fixed mixture of bacterial strains administrated with a rectal catheter.

Treatment:

Drug: Vancomycin

Drug: Rectal bacteriotherapy