Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT02112279 |
| Other study ID # |
PHC059 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
Phase 1
|
| First received |
April 9, 2014 |
| Last updated |
January 7, 2015 |
| Start date |
April 2014 |
| Est. completion date |
June 2015 |
Study information
| Verified date |
January 2015 |
| Source |
Providence Holy Cross Medical Center |
| Contact |
Robert B Moghimi, MD |
| Phone |
818-363-7120 |
| Email |
rbm10105[@]yahoo.com |
| Is FDA regulated |
No |
| Health authority |
United States: Food and Drug Administration |
| Study type |
Interventional
|
Clinical Trial Summary
Clostridium-difficile (C-difficile) is a gram positive anaerobic spore-forming bacterium
that can lead to severe diarrhea and pseudomembranous colitis. According to Schroeder
(2005), there are approximately 3 million cases annually with a mortality rate of 1-2.5 %.
It is most often associated with overuse of antibiotics. According to Bartlett & Gerding
(2008), 15-25% of anti-microbial-associated diarrhea is caused by C-difficile.
The purpose of this study is to determine if donor fecal microbiota transplant via
colonoscopy reduces refractory C-difficile infection better than current routine methods
such as continued antibiotic treatment. Specifically, we hypothesize that fecal microbiota
transplant via colonoscopy will result in a higher C-difficile cure rate in affected
patients versus care as usual in a retrospective cohort.
Description:
Background
Clostridium-difficile (C-difficile) is a gram positive anaerobic spore-forming bacterium
that can lead to severe diarrhea and pseudomembranous colitis. According to Schroeder
(2005), there are approximately 3 million cases annually with a mortality rate of 1-2.5 %.
It is most often associated with overuse of antibiotics. According to Bartlett & Gerding
(2008), 15-25% of anti-microbial-associated diarrhea is caused by C-difficile.
The purpose of this study is to determine if donor fecal microbiota transplant via
colonoscopy reduces refractory C-difficile infection better than current routine methods
such as continued antibiotic treatment. Specifically, we hypothesize that fecal microbiota
transplant via colonoscopy will result in a higher C-difficile cure rate in affected
patients versus care as usual in a retrospective cohort.
Current concerns with C-difficile
An increase in C-difficile exposure in hospital settings, especially for immune compromised
patients has been noted. The long life of C-difficile spores with poor ability for cleaning
agents to kill the spores is a particular concern for patients in critical care and oncology
units. In addition, although C-difficile has been considered a hospital acquired disease,
there has been an increase in community acquired C-difficile infection with the last few
years.
A concern was expressed by Muto, et al (2005) regarding the relationship between an
unexpected outbreak of C-difficile infection following an increase in fluoroquinalone use.
They found that exposure to levofloxacin was an independent risk factor for
C-difficile-associated diarrhea and appeared to contribute substantially to the outbreak.
They recommended restricted use of levofloxacin and the other implicated antibiotics to
control the outbreak. In 2005 the Center for Disease Control (CDC) issued a warning
regarding a new, highly toxic strain of C-difficile that was resistant to fluoroquinalone
antibiotics.
A study by Sethi, et al, (2010), demonstrated the difficulty in eradicating C-difficile
infections. In their study of fifty-two patients with C-difficile, the bacteria were
suppressed to undetectable levels in stool samples from most patients during treatment. At
1-4 weeks after treatment, 56% of patients who had samples tested were asymptomatic carriers
of C-difficile. They found that skin contamination and environmental shedding of C-difficile
often persist at the time of resolution of diarrhea, and recurrent shedding is common 1-4
weeks after therapy (58% for skin contamination and 50%, for environmental shedding).
Treatment with fecal microbiota Microbiotas are friendly, beneficial bacteria. Microbiotas
produce essential nutrients such as short-chain fatty acids; control epithelial cell growth;
prevent overgrowth of infectious organisms; boost intestinal immunity; and prevent
inflammation, diarrhea and other intestinal conditions. This essential ecosystem provides an
important balance between health and disease in the body. The goal for fecal microbial
transplant is to re-establish fecal microbial homeostasis with increased microbial
diversity.
Fecal microbiota transplants are a relatively new direction in treating C-difficile
infections (CDI) that are refractory to accepted antibiotic treatment. In a retrospective
medical record review of 70 patients with recurrent CDI who had undergone fecal
transplantation performed via colonoscopy, Matilla, et al (2011) concluded that fecal
transplantation through colonoscopy seems to be an effective treatment for recurrent CDI and
also for recurrent CDI caused by the virulent C-difficile 027 strain.
According to a systematic review of the literature, in 317 patients treated across 27 case
series and reports, intestinal microbiota transplant demonstrated disease resolution in 92%
of cases. Among the variables that determined procedural success were treatment prior to
procedure, relationship of the donor to the patient, route of fecal microbiota instillation
and amount of fecal microbiota solution delivered. (Gough, Shaikh & Manges, 2010).
A three-group study was conducted with 13 participants randomized to each group. Results
demonstrated resolution rates of C-difficile were (81%) for the vancomycin group with
subsequent donor fecal transplant via nasoduodenal tube; (31%) vancomycin only group; and
(23%) vancomycin with bowel lavage group; p<0.0001 (van Nood, et al; 2013).
In a published report of proceedings of a Canadian Working Group to discuss the issues of
fecal microbiota transplant, many important concerns were brought forward, including the
need for donor screening, standardization of the donor fecal transplant material and the use
of biologic material as an un-approved drug (Allen-Vercoe, et al, 2012). These issues must
be addressed in any study to ensure that patient safety and study reliability are at the
forefront in the determination of the effectiveness of fecal transplant to treat C-difficile
infections that are refractory to approved antibiotic treatment.
Methods
This study is a one-group convenience sample interventional study with a qualitative
component.
Recruitment Active recruitment will involve one-to-one explanations with in-patients at a
community hospital and out-patients presenting one of the study physicians for care of
refractory C-difficile infection.
Procedures I. Participants
A. Patient:
1. Patients must be 18 years of age or older
2. Patient must have a positive C. difficile test within the 10 days prior to the
procedure.
3. Continued symptoms of c-difficile infection
4. Patients must have failed at least two courses of appropriate antibiotic therapy for C.
diff to be a candidate for this procedure.
5. Informed consent must be obtained.
6. All antibiotics must be discounted at least 72 hours prior to the infusion. The patient
may continue on proton pump inhibitors (PPIs) but their use should be noted pre- and
post- transplant.
7. A standard colonoscopy prep will be given the day before the procedure (Laxative
regimen and clear liquids only).
8. Patient must provide a clean, dry blender that will be used to blend the stool mixture.
The blender will be discarded after use and will not be re-used.
B. Donor: if Familial versus purchased donor stool
1. The donor must be 18 years of age or older.
2. The closer the relationship between the donor and the recipient the better. Spouses and
partners, first degree relatives, or household members are preferred.
3. Donors must have no history of Hepatitis B or C, HIV, recent communicable disease,
incarceration, high-risk sexual behavior, inflammatory bowel disease, gastrointestinal
malignancy or colon polyps. They may not have traveled an area known to be endemic for
diarrheal illnesses in the past 6 months, taken antibiotics in the past 3 months for
any reason, or be on any immunosuppressive drugs or chemotherapy.
4. Donors must test negative for Hepatitis B and C and HIV, and have stool specimens
negative for C. Difficile, Campylobacter, Salmonella, Shigella, ova and parasites,
other pathogenic bacteria, giardia antigen and cryptosporidium antigen within 10 days
prior to the procedure.
5. Informed consent must be obtained from the donor.
II. Setting A. A Gastroenterology Laboratory in an acute care 377-bed non-teaching hospital.
III. Procedure A. Prior to Procedure
1. Verify physician order for Bowel Recolonization Therapy (or Fecal Bacteriotherapy) via
colonoscopy.
2. Stool from donor must be brought in to the hospital in an approved container, received
by hospital staff, labeled with the donors name, the recipients name and the recipients
medical record number and sent to Endoscopy for preparation for procedure.
a) The stool from donor should be formed and of adequate quantity. b) The stool from
donor should be collected as close in time to instillation as possible, preferably
within 6-8 hours of the procedure.
3. Informed consent must be obtained from the donor and the recipient. B. Preparation of
donor sample
1. Personal protective equipment (mask, eye protection, gown and gloves) must be worn
throughout the preparation procedure
2. Blend stool and non-bacteriostatic normal saline in a blender until stool reaches a
liquid slurry consistency. Add more non-bacteriostatic normal saline until desired
consistency achieved. The stool should be blended to the approximate consistency of a
milkshake.
3. Filter stool solution into a sterile container with 6 layers of gauze pads, removing as
much particulate matter as possible
4. Large volumes of 300-700 ml should be used for delivery through the colonoscope into
the cecum or terminal ileum.
5. Container with fecal slurry must be labeled with recipients identification information
and delivered immediately to bedside for instillation.
C. Instillation via Colonoscopy
1. Stool mixture is administered into the terminal ileum and cecum through the biopsy
channel of a colonoscope while the patient is sedated.
1. Equipment:
(1) 5 syringes (at least 60 cc each) (2) K-Y jelly or water-soluble lubricant (3) Chux
pads (4) Exam gloves
2. Complete hand hygiene.
3. Verify correct patient by using two patient identifiers.
4. Put on gloves and place a drape/chux under the patients buttocks.
5. Administer 300-700 ml of slurry through biopsy channel of colonoscope with a piston
syringe.
6. Dispose of any leftover slurry into toilet. Dispose of waste.
7. Remove gloves and complete hand hygiene.
8. Document
1. Date and time of procedure
2. Amount of fecal slurry administered.
3. Results and patients response to procedure.
4. Observe patient for at least 15-30 minutes, until VS are stable.
Measurement and data collection
1. All study patients will keep a stool diary for the 30 days following the
transplant noting number of stools, time of passage, character of stool, and any
changes in the patients quality of life.
2. All study patients will have a C. difficile toxin determination test at 14 days
and 28 days after the procedure per physician order. C. difficile testing may be
conducted using one of three methods: PCR, Illumegene, or EIA.
3. Recurrence of C. difficile is determined by C. difficile tests, signs and
symptoms, as well as the consistency of stools produced.
4. Study patients will be contacted at 7, 14 and 28 days following the procedure for
any concerns. A self-addressed envelope will be provided to the study participants
to return their completed post-procedures log to the research team after 28 days.
5. Records for patients who undergo this procedure will be maintained by the research
team in a secure location.
Analysis Data analysis will be completed using measures of central tendency and
raw percentages. Results of the post-procedure phone calls and the patient logs
will be analyzed using qualitative measures based on phenomenology and measures of
central tendency for quantitative aspects.
