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

NCT02774382 | Unknown Phase 3 DMC

• 1 other identifier: SJ-478
• Study Type: interventional
• Target: 450
• Locations: 1 country
• Sites: 2

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.

Conditions

Clostridium Difficile

Keywords

Recurrence; Infection

Outcome Measures

Primary Outcomes (1)

• Clinical 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.

  90 days

Secondary Outcomes (15)

• 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

• 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

Study Arms (3)

Vancomycin

ACTIVE COMPARATOR

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

Drug: Vancomycin

Vancomycin + fecal microbiota transplantation

EXPERIMENTAL

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.

Drug: Vancomycin; Drug: Fecal microbiota transplantation

Vancomycin + rectal bacteriotherapy

EXPERIMENTAL

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.

Drug: Vancomycin; Drug: Rectal bacteriotherapy

Interventions

Vancomycin DRUG

Already incl. in arm description

Vancomycin; Vancomycin + fecal microbiota transplantation; Vancomycin + rectal bacteriotherapy

Fecal microbiota transplantation DRUG

Already incl. in arm description

Vancomycin + fecal microbiota transplantation

Rectal bacteriotherapy DRUG

Already incl. in arm description

Vancomycin + rectal bacteriotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Hvidovre University Hospital: lead

Study Sites (2)

Hvidovre Hospital

Hvidovre, 2650, Denmark

RECRUITING

Køge sygehus

Køge, 4600, Denmark

RECRUITING

Related Publications (6)

• Kelly CP, LaMont JT. Clostridium difficile--more difficult than ever. N Engl J Med. 2008 Oct 30;359(18):1932-40. doi: 10.1056/NEJMra0707500. No abstract available.

  PMID: 18971494 BACKGROUND

• Lessa FC, Mu Y, Bamberg WM, Beldavs ZG, Dumyati GK, Dunn JR, Farley MM, Holzbauer SM, Meek JI, Phipps EC, Wilson LE, Winston LG, Cohen JA, Limbago BM, Fridkin SK, Gerding DN, McDonald LC. Burden of Clostridium difficile infection in the United States. N Engl J Med. 2015 Feb 26;372(9):825-34. doi: 10.1056/NEJMoa1408913.

  PMID: 25714160 BACKGROUND

• Olsen MA, Yan Y, Reske KA, Zilberberg MD, Dubberke ER. Recurrent Clostridium difficile infection is associated with increased mortality. Clin Microbiol Infect. 2015 Feb;21(2):164-70. doi: 10.1016/j.cmi.2014.08.017. Epub 2014 Oct 12.

  PMID: 25658560 BACKGROUND

• van Nood E, Vrieze A, Nieuwdorp M, Fuentes S, Zoetendal EG, de Vos WM, Visser CE, Kuijper EJ, Bartelsman JF, Tijssen JG, Speelman P, Dijkgraaf MG, Keller JJ. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med. 2013 Jan 31;368(5):407-15. doi: 10.1056/NEJMoa1205037. Epub 2013 Jan 16.

  PMID: 23323867 BACKGROUND

• Cammarota G, Masucci L, Ianiro G, Bibbo S, Dinoi G, Costamagna G, Sanguinetti M, Gasbarrini A. Randomised clinical trial: faecal microbiota transplantation by colonoscopy vs. vancomycin for the treatment of recurrent Clostridium difficile infection. Aliment Pharmacol Ther. 2015 May;41(9):835-43. doi: 10.1111/apt.13144. Epub 2015 Mar 1.

  PMID: 25728808 BACKGROUND

• Tvede M, Tinggaard M, Helms M. Rectal bacteriotherapy for recurrent Clostridium difficile-associated diarrhoea: results from a case series of 55 patients in Denmark 2000-2012. Clin Microbiol Infect. 2015 Jan;21(1):48-53. doi: 10.1016/j.cmi.2014.07.003. Epub 2014 Oct 12.

  PMID: 25636927 BACKGROUND

MeSH Terms

Conditions

Recurrence; Infections

Interventions

Vancomycin; Fecal Microbiota Transplantation

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Glycopeptides; Glycoconjugates; Carbohydrates; Peptides; Amino Acids, Peptides, and Proteins; Biological Therapy; Therapeutics

Study Officials

• Andreas M Petersen, MD PhD

  Hvidovre University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Andreas M Petersen, MD, PhD

CONTACT

+4538625960; andreasmunkpetersen@regionh.dk

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: April 4, 2016
• First Posted: May 17, 2016
• Study Start: May 1, 2017
• Primary Completion: December 1, 2018
• Study Completion: January 1, 2019
• Last Updated: September 27, 2017

Record last verified: 2017-09

Locations

DK (2)