FMT Versus Antimicrobials for Initial Treatment of Recurrent CDI

NCT02255305 | Terminated Phase 2 Results DMC

• 1 other identifier: EH 14-331
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to determine the safety and efficacy of Fecal Microbiota Transplant (FMT) for the treatment of the recurrence of Clostridium difficile infection (CDI) as compared to standard antibiotic therapy. Patients who have tested positive for CDI within 90 days of an admission for relapse of CDI will be approached to participate in this open-label, randomized controlled trial. Patients will either be randomized to the intervention group (receive FMT via retention enema) or the control group (receive antimicrobials targeting CDI).

Conditions

Clostridium Difficile Infection

Keywords

CDI; C difficile; C diff; Clostridium difficile

Outcome Measures

Primary Outcomes (1)

• Number of Patients With Clinical Resolution of Diarrhea

  Number of patients with resolution of diarrhea and other abdominal symptoms or return to baseline symptoms that were present prior to C. difficile diagnosis

  90 days

Secondary Outcomes (4)

• Time to Clinical Resolution of Symptoms

  90 days

• Hospital Length of Stay

  90 days

• Number of Patients With Hospital Readmission

  90 days

• Mortality

  90 days

Study Arms (2)

FMT Group (Intervention Arm)

EXPERIMENTAL

Patients randomized to the FMT group will have antimicrobials targeting C. difficile discontinued at least 6 hours prior to undergoing an FMT via retention enema. A second FMT via retention enema will be administered at 24 hours if diarrhea persists.

Biological: FMT

Antimicrobial Group (Control Arm)

ACTIVE COMPARATOR

Patients randomized to the antimicrobial group will be treated with antibiotics targeting C. difficile according to the Society for Healthcare Epidemiology of America (SHEA) Clinical Practice Guidelines for CDI. FMT will be offered to this group after 90 days if they experience relapsing CDI.

Drug: Antimicrobials

Interventions

FMT BIOLOGICAL

Patients in the FMT group will receive \~50 grams of fecal material suspended in bacteriostatic normal saline and glycerol.

Also known as: Fecal Microbiota Transplant, Stool Transplant

FMT Group (Intervention Arm)

Antimicrobials DRUG

Patients randomized to the control group will receive antimicrobials targeting C. difficile.

Antimicrobial Group (Control Arm)

Eligibility Criteria

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

You may qualify if:

• Diagnosis of active C. difficile infection, defined as \> 3 diarrheal stools per day and a positive C. difficile PCR assay
• Hospitalized patient presenting with first relapse of CDI occuring between 15 and 90 days after an index episode of CDI

You may not qualify if:

• Pregnancy
• Neutropenia (absolute neutrophil count \<1000/microliters)
• Contraindication for retention enema
• Food allergy not controlled in the donor diet

Sponsors & Collaborators

• Endeavor Health: lead

Study Sites (1)

NorthShore University HealthSystem

Evanston, Illinois, 60201, United States

Location

Related Publications (16)

• Dallal RM, Harbrecht BG, Boujoukas AJ, Sirio CA, Farkas LM, Lee KK, Simmons RL. Fulminant Clostridium difficile: an underappreciated and increasing cause of death and complications. Ann Surg. 2002 Mar;235(3):363-72. doi: 10.1097/00000658-200203000-00008.

  PMID: 11882758 BACKGROUND

• Dubberke ER, Reske KA, Olsen MA, McDonald LC, Fraser VJ. Short- and long-term attributable costs of Clostridium difficile-associated disease in nonsurgical inpatients. Clin Infect Dis. 2008 Feb 15;46(4):497-504. doi: 10.1086/526530.

  PMID: 18197759 BACKGROUND

• Kuijper EJ, Coignard B, Tull P; ESCMID Study Group for Clostridium difficile; EU Member States; European Centre for Disease Prevention and Control. Emergence of Clostridium difficile-associated disease in North America and Europe. Clin Microbiol Infect. 2006 Oct;12 Suppl 6:2-18. doi: 10.1111/j.1469-0691.2006.01580.x.

  PMID: 16965399 BACKGROUND

• Loo VG, Poirier L, Miller MA, Oughton M, Libman MD, Michaud S, Bourgault AM, Nguyen T, Frenette C, Kelly M, Vibien A, Brassard P, Fenn S, Dewar K, Hudson TJ, Horn R, Rene P, Monczak Y, Dascal A. A predominantly clonal multi-institutional outbreak of Clostridium difficile-associated diarrhea with high morbidity and mortality. N Engl J Med. 2005 Dec 8;353(23):2442-9. doi: 10.1056/NEJMoa051639. Epub 2005 Dec 1.

  PMID: 16322602 BACKGROUND

• McDonald LC, Owings M, Jernigan DB. Clostridium difficile infection in patients discharged from US short-stay hospitals, 1996-2003. Emerg Infect Dis. 2006 Mar;12(3):409-15. doi: 10.3201/eid1205.051064.

  PMID: 16704777 BACKGROUND

• Musher DM, Aslam S, Logan N, Nallacheru S, Bhaila I, Borchert F, Hamill RJ. Relatively poor outcome after treatment of Clostridium difficile colitis with metronidazole. Clin Infect Dis. 2005 Jun 1;40(11):1586-90. doi: 10.1086/430311. Epub 2005 Apr 25.

  PMID: 15889354 BACKGROUND

• Pepin J, Valiquette L, Alary ME, Villemure P, Pelletier A, Forget K, Pepin K, Chouinard D. Clostridium difficile-associated diarrhea in a region of Quebec from 1991 to 2003: a changing pattern of disease severity. CMAJ. 2004 Aug 31;171(5):466-72. doi: 10.1503/cmaj.1041104.

  PMID: 15337727 BACKGROUND

• Brandt LJ, Aroniadis OC. An overview of fecal microbiota transplantation: techniques, indications, and outcomes. Gastrointest Endosc. 2013 Aug;78(2):240-9. doi: 10.1016/j.gie.2013.03.1329. Epub 2013 May 2. No abstract available.

  PMID: 23642791 BACKGROUND

• Konijeti GG, Sauk J, Shrime MG, Gupta M, Ananthakrishnan AN. Cost-effectiveness of competing strategies for management of recurrent Clostridium difficile infection: a decision analysis. Clin Infect Dis. 2014 Jun;58(11):1507-14. doi: 10.1093/cid/ciu128. Epub 2014 Mar 31.

  PMID: 24692533 BACKGROUND

• Chang JY, Antonopoulos DA, Kalra A, Tonelli A, Khalife WT, Schmidt TM, Young VB. Decreased diversity of the fecal Microbiome in recurrent Clostridium difficile-associated diarrhea. J Infect Dis. 2008 Feb 1;197(3):435-8. doi: 10.1086/525047.

  PMID: 18199029 BACKGROUND

• Gough E, Shaikh H, Manges AR. Systematic review of intestinal microbiota transplantation (fecal bacteriotherapy) for recurrent Clostridium difficile infection. Clin Infect Dis. 2011 Nov;53(10):994-1002. doi: 10.1093/cid/cir632.

  PMID: 22002980 BACKGROUND

• 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.

  PMID: 23511459 BACKGROUND

• Hamilton MJ, Weingarden AR, Sadowsky MJ, Khoruts A. Standardized frozen preparation for transplantation of fecal microbiota for recurrent Clostridium difficile infection. Am J Gastroenterol. 2012 May;107(5):761-7. doi: 10.1038/ajg.2011.482. Epub 2012 Jan 31.

  PMID: 22290405 BACKGROUND

• Youngster I, Sauk J, Pindar C, Wilson RG, Kaplan JL, Smith MB, Alm EJ, Gevers D, Russell GH, Hohmann EL. Fecal microbiota transplant for relapsing Clostridium difficile infection using a frozen inoculum from unrelated donors: a randomized, open-label, controlled pilot study. Clin Infect Dis. 2014 Jun;58(11):1515-22. doi: 10.1093/cid/ciu135. Epub 2014 Apr 23.

  PMID: 24762631 BACKGROUND

• Kelly CR, Kunde SS, Khoruts A. Guidance on preparing an investigational new drug application for fecal microbiota transplantation studies. Clin Gastroenterol Hepatol. 2014 Feb;12(2):283-8. doi: 10.1016/j.cgh.2013.09.060. Epub 2013 Oct 6.

  PMID: 24107393 BACKGROUND

• Cohen SH, Gerding DN, Johnson S, Kelly CP, Loo VG, McDonald LC, Pepin J, Wilcox MH; Society for Healthcare Epidemiology of America; Infectious Diseases Society of America. Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the society for healthcare epidemiology of America (SHEA) and the infectious diseases society of America (IDSA). Infect Control Hosp Epidemiol. 2010 May;31(5):431-55. doi: 10.1086/651706.

  PMID: 20307191 BACKGROUND

MeSH Terms

Conditions

Clostridium Infections

Interventions

Fecal Microbiota Transplantation; Anti-Infective Agents

Condition Hierarchy (Ancestors)

Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Biological Therapy; Therapeutics; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses

Limitations and Caveats

Study ended early due to personnel needed for study completion (enrollment, follow-up, FMT procedure) and did not reach enrollment goals.

Results Point of Contact

• Title: Jennifer Grant
• Organization: NorthShore UH

jgrant@northshore.org

847-570-2420

Study Officials

• Becky Smith, MD

  Endeavor Health

  PRINCIPAL INVESTIGATOR

• Jennifer Grant, MD

  Endeavor Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Hospital Epidemiologist

Study Record Dates

• First Submitted: September 30, 2014
• First Posted: October 2, 2014
• Study Start: January 1, 2015
• Primary Completion: January 1, 2020
• Study Completion: January 1, 2020
• Last Updated: March 3, 2023
• Results First Posted: March 3, 2023

Record last verified: 2023-02

Locations

US (1)