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IMT for Primary Clostridium Difficile Infection

Information source: Oslo University Hospital
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Clostridium Difficile Infection

Intervention: Intestinal microbiota therapy (Biological); Metronidazole (Drug)

Phase: N/A

Status: Recruiting

Sponsored by: Oslo University Hospital

Official(s) and/or principal investigator(s):
Michael Bretthauer, Ph.d., Study Chair, Affiliation: University of Oslo

Overall contact:
Kjetil K Garborg, MD, Email: k.k.garborg@medisin.uio.no

Summary

This is a randomized controlled trial to compare the effect of a 10-day course of per oral Metronidazole versus a one-time rectal instillation of an anaerobically cultivated human intestinal microbiota for the treatment of a first occurrence of clostridium difficile infection (CDI). Recurrent CDI is common after standard antibiotic treatment. We hypothesize that the instillation of a healthy intestinal microbiota will be more effective in inducing a durable cure than Metronidazole for primary CDI.

Clinical Details

Official title: Intestinal Microbiota Therapy Versus Metronidazole for Primary Clostridium Difficile Infection: a Randomized Controlled Trial

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Treatment

Primary outcome: Number of participants with cure without recurrence

Secondary outcome:

Number of participants without diarrhea

Number of participants in which there was a need to change treatment

Detailed description: Up to one third of patients with clostridium difficile infection treated with antibiotics experience recurrent or relapsing symptoms within a few weeks. Even with subsequent antibiotic treatment, multiple recurrences/relapses are frequent. Fecal microbiota transplantation (FMT) has been shown to be significantly more effective in curing recurrent CDI than repeated antibiotic treatment. In current guidelines, FMT is proposed as a treatment option after multiple recurrences/relapses of CDI. The rationale to reserve transplantation of donor feces for recurrent and difficult cases of CDI is a possible risk of pathogen transmittance and the cumbersome and costly process of finding a donor and screen for communicable disease. The effect of FMT for recurrent CDI, however, suggests that this therapy may be more effective than antibiotics in inducing a durable cure also for primary CDI. We aim to use an anaerobically cultivated human intestinal microbiota (ACHIM) that has been extensively tested for pathogens, from a donor screened for communicable diseases, to avoid the need for a case-by-case donor screening. The term Intestinal Microbiota Therapy (IMT) will be used to describe the ACHIM treatment. Patients with a first occurrence of CDI defined by diarrhea, as defined by the World Health Organization, and a positive stool test for Clostridium difficile toxin A or B will be randomized 1: 1 to either a 10-day course of Metronidazole 500 mg t. i.d. or a rectal instillation of 60 ml ACHIM suspension. Patients will be contacted on day 4 by an unblinded study investigator and on days 35 and 70 by a blinded study investigator to evaluate the treatment effect. In addition, the patients will register the frequency of bowel movements on days 1-4, 7, 14 and 21. In the case of clinical deterioration, appropriate measures will be undertaken according to current guidelines. A second instillation of ACHIM suspension will be considered on day 4 in the absence of clinical improvement. The primary endpoint is the rate of primary cure from CDI and no sign of relapse/recurrence within 70 days, or persistent diarrhea that could be explained by other causes with three consecutive negative stool tests for C. difficile toxin A or B. Treatment failure is defined as persistent diarrhea with a positive stool test for C. difficile toxin A or B. Relapsing or recurrent CDI is defined as diarrhea and a positive stool test for C. difficile toxin within 70 days of treatment initiation after an initial resolution of diarrhea. Preliminary sample size is estimated from a hypothesis of a primary cure rate without recurrence within 70 days of 75 % with Metronidazole vs. 87. 5 % with IMT. An interim analysis is planned after inclusion of the first 40 patients to guide the final sample size estimation. Patients will be recruited at six hospitals in South-East Norway.

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Diarrhea as defined by the World Health Organization (passage of 3 or more loose or

liquid stools (i. e. taking the shape of the receptacle or corresponding to Bristol stool chart types 5-7) per day, or more frequently than is normal for the individual, and

- Positive fecal clostridium difficile toxin A or B test, and

- No evidence of CDI during the previous year.

Exclusion Criteria:

- Known presence of other stool pathogens known to cause diarrhea.

- Pregnancy and nursing.

- Patients with ongoing antibiotic treatment for other infections that cannot be

stopped for at least 12 hours.

- Inflammatory bowel disease.

- Patients incapable of providing informed consent.

- Patients with <3 months life expectancy.

- Serious immunodeficiency caused by chemotherapy or other medication.

- Active immunocompromising disease.

- Patients unable to comply with protocol requirements.

- Patients in need of intensive care who are American Society of Anesthesiologists

(ASA) Physical Status classification IV and V.

- Known hypersensitivity to Metronidazole

Locations and Contacts

Kjetil K Garborg, MD, Email: k.k.garborg@medisin.uio.no

Vestre Viken HF, Bærum Hospital, Bærum, Norway; Not yet recruiting
Øystein Rose, MD

Sørlandet Hospital HF, Kristiansand, Norway; Not yet recruiting
Håvard Wiig, MD

Diakonhjemmet Hospital, Oslo, Norway; Not yet recruiting
Jonas Koch, MD

Oslo University Hospital, Oslo, Norway; Recruiting
Kjetil K Garborg, MD, Email: k.k.garborg@medisin.uio.no
Siv Furholm, RN, Email: siv.furholm@medisin.uio.no

Telemark Hospital HF, Skien, Norway; Recruiting
Hilde Skudal, MD

Additional Information

Related publications:

van Nood E, Dijkgraaf MG, Keller JJ. Duodenal infusion of feces for recurrent Clostridium difficile. N Engl J Med. 2013 May 30;368(22):2145. doi: 10.1056/NEJMc1303919.

Kassam Z, Lee CH, Yuan Y, Hunt RH. Fecal microbiota transplantation for Clostridium difficile infection: systematic review and meta-analysis. Am J Gastroenterol. 2013 Apr;108(4):500-8. doi: 10.1038/ajg.2013.59. Epub 2013 Mar 19. Review.

Jorup-Rönström C, Håkanson A, Sandell S, Edvinsson O, Midtvedt T, Persson AK, Norin E. Fecal transplant against relapsing Clostridium difficile-associated diarrhea in 32 patients. Scand J Gastroenterol. 2012 May;47(5):548-52. doi: 10.3109/00365521.2012.672587. Epub 2012 Apr 2.

Lund-Tønnesen S, Berstad A, Schreiner A, Midtvedt T. [Clostridium difficile-associated diarrhea treated with homologous feces]. Tidsskr Nor Laegeforen. 1998 Mar 10;118(7):1027-30. Norwegian.

Garborg K, Waagsbø B, Stallemo A, Matre J, Sundøy A. Results of faecal donor instillation therapy for recurrent Clostridium difficile-associated diarrhoea. Scand J Infect Dis. 2010 Dec;42(11-12):857-61. doi: 10.3109/00365548.2010.499541. Epub 2010 Jul 22.

Midtvedt T, Norin E, Benno P, Dahlgren AL. Response to Surawicz et al. Am J Gastroenterol. 2013 Dec;108(12):1931-2. doi: 10.1038/ajg.2013.280.

Starting date: November 2014
Last updated: February 4, 2015

Page last updated: August 23, 2015

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