Fecal Microbiota Transplantation by Colonoscopy for Recurrent C. Difficile Infection

NCT ID: NCT02148601

Last Updated: 2020-07-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 39 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-07-31
• Study Completion Date: 2014-11-30

Brief Summary

In the recent past, a deep change in the epidemiology of C. difficile infection has occurred, with a rise in its frequency, severity, and mortality. Both the refractoriness of the infection to standard therapy and its probability of recurrence have also increased, representing a main clinical issue. Fecal microbiota transplantation (FMT) refers to the introduction of a liquid filtrate of stools from a healthy donor into the gastrointestinal tract of a patient for the treatment of specific diseases. FMT has shown outstanding results in the treatment of recurrent C. difficile infection. It can be performed through various routes: nasogastric or nasojejunal tube, upper endoscopy, retention enema, colonoscopy. In a recent systematic review of studies using FMT for the treatment of recurrent C. difficile infection, Cammarota et al. observed that lower gastrointestinal route (colonoscopy, enema) led to the achievement of higher eradication rates than upper delivery (gastroscopy, naso-gastric or naso-jejunal tube) (81-86% vs 84-93%, respectively). In a randomized clinical trial, Van Nood et al. showed the efficacy of FMT by nasojejunal tube in recurrent C. difficile infection. Up to now, data on FMT by lower route come out only by case series and case reports.

The investigators' aim is to compare the efficacy of colonoscopic FMT and standard antibiotic therapy for the treatment of C. difficile infection in a randomized clinical trial

Detailed Description

In the recent past, a deep change in the epidemiology of C. difficile infection has occurred, with a rise in its frequency, severity, and mortality. Both the refractoriness of the infection to standard therapy and its probability of recurrence have also increased, representing a main clinical issue. Fecal microbiota transplantation (FMT) refers to the introduction of a liquid filtrate of stools from a healthy donor into the gastrointestinal tract of a patient for the treatment of specific diseases. FMT has shown outstanding results in the treatment of recurrent C. difficile infection. It can be performed through various routes: nasogastric or nasojejunal tube, upper endoscopy, retention enema, colonoscopy. In a recent systematic review of studies using FMT for the treatment of recurrent C. difficile infection, Cammarota et al. observed that lower gastrointestinal route (colonoscopy, enema) led to the achievement of higher eradication rates than upper delivery (gastroscopy, naso-gastric or naso-jejunal tube) (81-86% vs 84-93%, respectively). In a randomized clinical trial, Van Nood et al. showed the efficacy of FMT by nasojejunal tube in recurrent C. difficile infection. Up to now, data on FMT by lower route come out only by case series and case reports.

The investigators' aim is to compare the efficacy of colonoscopic FMT and standard antibiotic therapy for the treatment of C. difficile infection in an open-label randomized clinical trial The investigators' trial should confirm the clinical results obtained by Van Nood et al. by using a colonoscopy approach.

The investigators' study is an open-label randomized controlled trial, enrolling patients with recurrent C. difficile infection, who are candidates for further antibiotic treatment in accordance with guidelines. Recurrent C. difficile infection is meant as the reappearance of clinical symptoms and positivity of C. difficile toxin test within 8 weeks after the end of the previous therapy. Patients' stool will be screened for detection of parasites and enteric bacterial pathogens to exclude other infective pathogens. Patients with severe clinical features (sepsis, severe dehydration, major co-morbidities), former colectomy, high-risk of endoscopic complications, inflammatory bowel diseases (IBD), irritable bowel syndrome (IBS), viral hepatitis, AIDS or syphilis will be excluded.

Patients will be instructed and invited to signal recurrent symptoms and diarrhea after treatment. Monthly clinical and lab checks will be performed for a period of six months after the treatment.

Treatment procedures:

All patients will start therapy with vancomycin for four days before of stratification, with random allocation (1 to 1) to one of the two treatment schemes: 1) FMT, with the infusion in the cecum - through the biopsy channel - of 60-120 gr (depending on production) of donated feces, obtained from the donor within 6 hours from transplantation, and manually homogenized in 100/200 ml of physiological solution; or 2) standard vancomycin-based therapy according to the international recommendations. Colonoscopy will be performed by an expert endoscopist, with mucosal biopsy (when possible) for histology examination. Patients allocated to FMT arm will undergo preparation for colonoscopy (four liters of a solution with saline laxatives). All patient will be instructed on hygiene rules to be followed at the patient's domicile to avoid re-infections at home. Stool donors should preferably be patient's relatives or intimates, must not have taken antibiotics in the last 6 months, should not present significant intestinal symptoms of other intestinal diseases and must result negative at the serum screening for viral hepatitis, AIDS or syphilis. Their stool will be tested for C. difficile, enteric bacteria, intestinal protozoa and helminthes pathogens.

Conditions

Clostridium Difficile

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Fecal Microbiota Transplantation

Fecal microbiota transplantation from healthy donors will be infused by colonoscopy

Group Type: EXPERIMENTAL

Fecal Microbiota Transplantation

Intervention Type: OTHER

Vancomycin (before randomization)

Intervention Type: DRUG

Vancomycin will be administered in all patients for 5 days before randomization. Then, patients will be randomized in FMT Group or Standard Antibiotic therapy Group. Patients in the FMT Group will stop vancomycin 24 hours before the fecal microbiota transplantation. Patients in the Standard Antibiotic Therapy Group will continue vancomycin.

Standard Antibiotic Therapy

Standard antibiotic therapy according to European Guidelines (vancomycin and metronidazole) will be administered to the patients

Group Type: ACTIVE_COMPARATOR

Standard Antibiotic Therapy

Intervention Type: DRUG

Vancomycin (before randomization)

Intervention Type: DRUG

Vancomycin will be administered in all patients for 5 days before randomization. Then, patients will be randomized in FMT Group or Standard Antibiotic therapy Group. Patients in the FMT Group will stop vancomycin 24 hours before the fecal microbiota transplantation. Patients in the Standard Antibiotic Therapy Group will continue vancomycin.

Interventions

Fecal Microbiota Transplantation

Intervention Type: OTHER

Standard Antibiotic Therapy

Intervention Type: DRUG

Vancomycin (before randomization)

Vancomycin will be administered in all patients for 5 days before randomization. Then, patients will be randomized in FMT Group or Standard Antibiotic therapy Group. Patients in the FMT Group will stop vancomycin 24 hours before the fecal microbiota transplantation. Patients in the Standard Antibiotic Therapy Group will continue vancomycin.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Symptomatic recurrent C. difficile infection identified by positivity of C. difficile toxin in stools (ELISA)
• Possibility to undergo standard antimicrobial therapy for recurrent C. difficile infection
• Approval of informed consent
• Possibility to undergo protocol diagnostic and therapeutic procedures
• Stool negativity for parasites
• Stool negativity for Salmonella spp., Shigella spp., Yersinia enterocolitica, Campylobacter, Streptococcus agalactiae, Staphylococcus aureus, enteropathogenic Escherichia coli and other microorganisms except for C. difficile
• Blood negativity for: Hepatitis A virus-Immunoglobulin M, HBsAg, Anti-Hepatitis C Virus, Anti-Human Immunodeficiency Virus1-2, venereal disease reaction level (VDRL).

Exclusion Criteria

• Subjects <18 years old
• Main comorbidities
• Prior colectomy
• Negativity of C. difficile toxin in stools
• High risk of post-colonoscopy complications
• Other main gastrointestinal diseases (es. Crohn's disease or ulcerative colitis)
• Stool positivity for parasites
• Stool positivity for Salmonella spp., Shigella spp., Yersinia enterocolitica, Campylobacter, Streptococcus agalactiae, Staphylococcus aureus, enteropathogenic Escherichia coli and other microorganisms except for C. difficile
• Blood positivity for: Hepatitis A virus-Immunoglobulin M, HBsAg, Anti-Hepatitis C Virus, Anti-Human Immunodeficiency Virus1-2, venereal disease reaction level (VDRL).
• Pregnancy or breastfeeding.
• Inability to follow protocol procedures

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 95 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Catholic University of the Sacred Heart

OTHER

Sponsor Role: lead

Responsible Party

Giovanni Cammarota

Prof. Giovanni Cammarota

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Catholic University of Sacred Heart - "A. Gemelli" University Hospital

Rome, , Italy

Countries

Italy

References

Cammarota G, Ianiro G, Bibbo S, Gasbarrini A. Gut microbiota modulation: probiotics, antibiotics or fecal microbiota transplantation? Intern Emerg Med. 2014 Jun;9(4):365-73. doi: 10.1007/s11739-014-1069-4. Epub 2014 Mar 25.

Reference Type: BACKGROUND

PMID: 24664520 (View on PubMed)

Cammarota G, Ianiro G, Gasbarrini A, Masucci L, Sanguinetti M. Faecal transplantation for Clostridium difficile infection. Three cases treated in Italy. Dig Liver Dis. 2014 May;46(5):475. doi: 10.1016/j.dld.2013.12.011. Epub 2014 Jan 20. No abstract available.

Reference Type: BACKGROUND

PMID: 24457126 (View on PubMed)

Cammarota G, Ianiro G, Gasbarrini A. Fecal microbiota transplantation for the treatment of Clostridium difficile infection: a systematic review. J Clin Gastroenterol. 2014 Sep;48(8):693-702. doi: 10.1097/MCG.0000000000000046.

Reference Type: BACKGROUND

PMID: 24440934 (View on PubMed)

Other Identifiers

A1192013

Identifier Type: -

Identifier Source: org_study_id