Efficacy and Safety of Fecal Microbiota Transplantation for Severe Clostridium Difficile Associated Colitis
Primary Purpose
Clostridium Difficile
Status
Terminated
Phase
Not Applicable
Locations
Israel
Study Type
Interventional
Intervention
fecal microbiota transplantation
Sponsored by
About this trial
This is an interventional treatment trial for Clostridium Difficile focused on measuring Clostridium difficile associated disease, fecal microbiota transplantation
Eligibility Criteria
Inclusion Criteria:
- Both genders are eligible for study
- Age 18 years and older
- Able to provide written, informed consent
- Confirmed diagnosis of severe CDAD as defined above
Exclusion Criteria:
(If any of the following apply, the subject MUST NOT enter the study):
- Pregnant or lactating women
- Need for prolonged antibiotics for other cause
- Other known etiology for diarrhea, or clinical infection with other known enteric pathogens
- Active, chronic conditions such as: Inflammatory bowel disease, Crohn's disease, Short bowel syndrome, Ulcerative or ischemic colitis
- Laxatives or motility-altering drugs within 12 hours of enrolment
- Clinically unstable. Hemodynamic instability defined as hypotension (mean arterial pressure < 60) not responsive to fluids.
- Any condition that, in the opinion of the investigator, would preclude safe participation in the trial or compromise the quality of the data obtained.
- Immune suppression, HIV, hematological or solid malignancy (chemotherapy in the past 3 months).
- Prior colon surgery
Sites / Locations
- Hadassah Medical Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
fecal microbiota transplant
Arm Description
fecal microbiota transplantation
Outcomes
Primary Outcome Measures
Number of Participants With Resolution of Severe CDAD
Resolution of diarrhea, time to decrease in elevated WBC count
Number of Participants With Relapse of CDAD
Number of Participants with evidence of relapse of C. diff. associated diarrhea
Secondary Outcome Measures
All Cause Mortality
Need for Colectomy
Number of Participants who undergo colectomy due to CDAD
Morbidity
immediate colonoscopy-related complications, secondary infection
Full Information
NCT ID
NCT01959048
First Posted
October 7, 2013
Last Updated
August 7, 2019
Sponsor
Hadassah Medical Organization
1. Study Identification
Unique Protocol Identification Number
NCT01959048
Brief Title
Efficacy and Safety of Fecal Microbiota Transplantation for Severe Clostridium Difficile Associated Colitis
Official Title
Efficacy and Safety of Fecal Microbiota Transplantation for Severe Clostridium Difficile Associated Colitis
Study Type
Interventional
2. Study Status
Record Verification Date
August 2019
Overall Recruitment Status
Terminated
Why Stopped
FMT for study indication has been permitted by Israeli Ministry of Health
Study Start Date
April 2014 (Actual)
Primary Completion Date
January 2016 (Actual)
Study Completion Date
January 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Hadassah Medical Organization
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
Clostridium difficile has become one of the leading causes of hospital acquired infections, and is associated with increased mortality. Patients with C. difficile associated disease (CDAD) possess deficiencies in 'normal' fecal microbial composition, most likely as a result of earlier antibiotic usage. The current standard of care treatment for severe C. difficile, which consists of antibiotics, does not restore the microbiota. Restoration of the normal colonic microbiota by fecal microbiota transplantation (FMT) may enable reversion colonic microbial population to a more 'normal'state and lead to cure.
A few patients develop severe CDAD which may be complicated by adynamic ileus, or toxic megacolon. The management in this context is based on limited data, and for some the only available option is sub-total colectomy.
Although FMT is by no means a new therapeutic modality, there is limited information on its use for the treatment of acute CDAD, including severe CDAD. Because of the high morbidity and mortality associated with treatment of patients with severe CDAD, and because the evidence supporting the current recommendations is weak and based upon the demonstration that FMT is an effective strategy to re-establish a balanced intestinal microbiota with resultant cure of recurrent CDAD, we propose to study the efficacy and safety of FMT for severe CDAD.
Patients with severe CDAD can be divided into two operational groups; those that have diarrhea and those that suffer from adynamic ileus. We propose to apply FMT through colonoscopy for all patients because current data suggest that the overall success rate of FMT for recurrent CDAD with lower gastrointestinal tract FMT was higher than FMT through the upper gastrointestinal tract. In addition, for patients with adynamic ileus and toxic megacolon (i.e., the population with the highest CDAD-associated morbidity and mortality), intra-colonic FMT administration is the preferred alternative.
Detailed Description
Screening and Consent - Index cases:
Hospitalized patient with the diagnosis of severe CDAD
At screening visit the study investigator(s) will explain the study in detail, answer any questions the candidate may have, and give the candidate a consent form to read and sign.
After signing the consent form, the candidate subject will be asked to provide a complete medical history and undergo a physical examination.
Blood will be drawn for a complete blood count (CBC) and bacterial culture
Stool will be collected and archived for use for further analysis as deemed necessary by the principal investigator. All analyses will be performed in an anonymous coded method, without any disclosure of the patient identifiers.
Screening and Consent - Donors:
Identified by recipients, generally an intimate partner or adult family member
Willing to donate stool
Exclusion criteria (per questionnaire):
Had taken antibiotics within 90 days of the planned procedure
Fever, diarrhea, vomiting, or any other symptoms of infection, which occurred within the two weeks prior to the day of the procedure.
Known exposure to HIV or viral hepatitis (within the previous 12 months)
High-risk sexual behaviors (examples: sexual contact with anyone with HIV/AIDS or hepatitis, men who have sex with men, sex for drugs or money)
Use of illicit drugs
Tattoo or body piercing within 6 months
Incarceration within previous 12 months
Known current communicable disease
Risk factors for variant Creutzfeldt-Jakob disease
Gastrointestinal co-morbidities
History of inflammatory bowel disease
History of irritable bowel syndrome, idiopathic chronic constipation, or chronic diarrhea
History of gastrointestinal malignancy
Recent ingestion of a potential allergen (eg, nuts) where recipient has a known allergy to this agent
Systemic autoimmunity, for example, multiple sclerosis, connective tissue disease
Exclusion criteria (per laboratory assays):
Positive HIV, hepatitis C virus, hepatitis B virus, Syphilis antibodies
Stool culture positive for the enteropathogenic bacteria Salmonella, Shigella, or Campylobacter
Stool stain positive for Ova and Parasites
Stool positive for Giardia- and Entamoeba histolytica-specific antigens
Stool positive for C. difficile toxins
Fecal Microbiota Transplantation Protocol Donor
Provide informed consent (laxative administration)
Report symptoms of infection, which occur between screening and the day of the procedure
Take a single dose of osmotic laxative (one tablet of "Laxadin") on the evening before the procedure
Provide fresh stool, at least 50 grams
Recipient 1. Provide informed consent
Fecal solution preparation
Universal precautions (gown, gloves, eye protection) during stool processing
Fresh (<6 h) donor stool specimen
About 50 grams of donor stool, diluted and shaken vigorously in sterile Saline 0.9% to homogeneity.
Filter stool through gauze if necessary to remove large debris
Stool suspension drawn up into 50 mL slip-tip syringes
Procedure
Informed consent for colonoscopy obtained including the additional theoretical risk of infection related to fecal transfusion
Document that examination of the colon is not adequate for cancer screening purposes (stool infusion interferes with visualization)
Colonoscopy performed aiming to reach the cecum with or without decompression without bowel inflation. If the cecum is not reachable the injection will be performed at the most distal site.
No biopsies taken
Upon withdrawal, injection of the fecal suspension via the biopsy channel of a colonoscope, majority into the right colon. Deliver between 300-500 ml.
Post procedure
1. Patient encouraged to retain stool (if possible) for 4 hours
Clinical and laboratory follow up
A blood culture will be drawn immediately following the procedure
Subjects will be followed during hospitalization and after discharge for at least 30 days. Data on symptoms of CDAD, on-going medical history review, physical examination, and laboratory tests as described in Table 1 will be collected.
Safety will be assessed by monitoring the subjects for adverse events.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Clostridium Difficile
Keywords
Clostridium difficile associated disease, fecal microbiota transplantation
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
3 (Actual)
8. Arms, Groups, and Interventions
Arm Title
fecal microbiota transplant
Arm Type
Experimental
Arm Description
fecal microbiota transplantation
Intervention Type
Drug
Intervention Name(s)
fecal microbiota transplantation
Primary Outcome Measure Information:
Title
Number of Participants With Resolution of Severe CDAD
Description
Resolution of diarrhea, time to decrease in elevated WBC count
Time Frame
2 weeks
Title
Number of Participants With Relapse of CDAD
Description
Number of Participants with evidence of relapse of C. diff. associated diarrhea
Time Frame
2 weeks
Secondary Outcome Measure Information:
Title
All Cause Mortality
Time Frame
30 days
Title
Need for Colectomy
Description
Number of Participants who undergo colectomy due to CDAD
Time Frame
30 days
Title
Morbidity
Description
immediate colonoscopy-related complications, secondary infection
Time Frame
1 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Both genders are eligible for study
Age 18 years and older
Able to provide written, informed consent
Confirmed diagnosis of severe CDAD as defined above
Exclusion Criteria:
(If any of the following apply, the subject MUST NOT enter the study):
Pregnant or lactating women
Need for prolonged antibiotics for other cause
Other known etiology for diarrhea, or clinical infection with other known enteric pathogens
Active, chronic conditions such as: Inflammatory bowel disease, Crohn's disease, Short bowel syndrome, Ulcerative or ischemic colitis
Laxatives or motility-altering drugs within 12 hours of enrolment
Clinically unstable. Hemodynamic instability defined as hypotension (mean arterial pressure < 60) not responsive to fluids.
Any condition that, in the opinion of the investigator, would preclude safe participation in the trial or compromise the quality of the data obtained.
Immune suppression, HIV, hematological or solid malignancy (chemotherapy in the past 3 months).
Prior colon surgery
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jacob Strahilevitz, MD
Organizational Affiliation
Hadassah Medical Organization
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hadassah Medical Center
City
Jerusalem
ZIP/Postal Code
91120
Country
Israel
12. IPD Sharing Statement
Learn more about this trial
Efficacy and Safety of Fecal Microbiota Transplantation for Severe Clostridium Difficile Associated Colitis
We'll reach out to this number within 24 hrs