Recurrent Clostridium Difficile InfectionPhase 2/3NCT01226992
Oral Vancomycin Followed by Fecal Transplant Versus Tapering Oral Vancomycin
A Phase 2/3 study testing Vancomycin and Fecal Transplant in people with Recurrent Clostridium Difficile Infection and Laboratory Confirmed Clostridium Difficile Infection, run by University Health Network, Toronto at 1 site in Canada.
Trial summary
Recurrent CDI is a growing problem with few treatment options that provide lasting effect. Fecal transplantation has been shown in several case series to be successful in controlling recurrent CDI. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Recurrent Clostridium Difficile Infection, Laboratory Confirmed Clostridium Difficile Infection
- What is being tested?
- Vancomycin and Fecal Transplant
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 81 participants
- Where
- 1 siteCanada
- Study dates
- Oct 2010to Oct 2014
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Laboratory or pathology-confirmed diagnosis of recurrent C. difficile infection (CDI) with symptoms within the previous 60 days. Recurrent CDI is defined as:
- >/=2 episodes of CDI. Eligible patients must have had at least one treatment course with oral vancomycin (minimum 10 days of 500 mg total daily oral vancomycin).
- Symptoms of CDI include:
- Diarrhea (see below) OR
- Abdominal pain AND abdominal distension/bloating AND fever, systemic illness with no other reason for these symptoms
- Diarrhea will be self-reported and is defined as:
Show all 13Show fewer
- at least 6 watery feces in 36 hours OR
- 3 unformed feces in 24 hours for minimum 2 days OR
- 8 unformed feces over 48 hours
- Age 18 years or older
- Signed informed consent
- Able to travel to clinic for follow-up visit and/or adhere to study procedures
- Agrees to abstain from taking probiotic supplementations for medicinal reasons for the duration of the study and follow-up period. To clarify, dietary intake is acceptable (e.g. non-supplemented yogurt).
Who cannot join
- Planned participation in another clinical trial
- Patients with conditions such as neutropenia, graft versus host disease or severe immunocompromise, in whom enemas are contraindicated
- More than one episode of CDI that has been severe or rapid in onset, resulting in:
- intensive care unit admission
- Evidence of active, severe colitis (ie. ongoing diarrhea not responsive to oral vancomycin; hemorrhagic colitis) such that an enema is contraindicated (note that such patients may be eligible once their colitis is under control)
- Unable to tolerate fecal transplantation procedure for any other reason
Show all 21Show fewer
- Hypersensitivity or intolerance to oral vancomycin
- Patients with underlying chronic gastrointestinal diseases that cause diarrhea, such as:
- Inflammatory bowel disease
- Short gut syndrome
- Severe motility disorders
- Severe diverticular disease
- Other chronic diarrhea NYD
- Unable to record frequency of bowel movements
- Receiving an investigational medication
- Planned therapy in the next 120 days that may cause diarrhea (example: chemotherapy)
- Planned surgery requiring perioperative antibiotics within 120 days
- Pregnancy
- Requires the regular use of medications that affect bowel motility before onset of CDI (example: metoclopramide, narcotics, loperamide)
- Serious bleeding disorder, anticoagulant use that cannot be stopped temporarily for procedure (in consultation with prescribing physician) or serious platelet disorder (platelet counts below 50).
- Any condition that, in the opinion of the investigator, would pose a health risk to the subject.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase II/III Randomized Controlled Trial of Oral Vancomycin Followed by Fecal Transplantation Versus Tapering Oral Vancomycin for Recurrent Clostridium Difficile Infection (CDI)
Recurrent CDI is a growing problem with few treatment options that provide lasting effect. Fecal transplantation has been shown in several case series to be successful in controlling recurrent CDI. The current study is a non-blinded, randomized controlled trial comparing fecal transplantation with a 6 week taper of oral vancomycin for the treatment of refractory CDI. Approximately 146 patients will be enrolled over one year. Participants in the study will be followed for 120 days, and will be given the opportunity to cross over to the alternative intervention arm if a relapse in symptoms occurs. The primary outcome measure will be recurrence of toxin-confirmed CDI within 120 days of starting the intervention. Secondary outcomes include: early recurrence of symptoms within 14 days, relapse within 120 days (same strain of C. difficile), attributable mortality, hospitalization and serious adverse events.
Read the detailed description
The proposed trial is a single-centre, phase II/III, open, parallel-group, randomized controlled trial. To have an evaluable population of 114 participants and assuming a 20% loss to follow-up, approximately 146 patients will be randomized in a 1:1 ratio to receive either approximately 2 weeks of oral vancomycin followed by a single fecal transplant via enema (hereon referred to as the "fecal transplant arm") or a 6-week taper of oral vancomycin (hereon referred to as the "vancomycin taper arm"). The 2 weeks of vancomycin pre-treatment in the fecal transplant arm will allow for a fecal transplant donor to be screened for potentially transmissible infectious diseases (clinically and through blood and stool tests), in order to ensure appropriateness and safety of donation.
If patients fail treatment during the follow-up period of 120 days, they will be offered the opportunity to cross over to the alternate treatment arm. Those who cross over will be followed for an additional 120 days from the second intervention.
Participants will be assessed clinically for recurrence in CDI symptoms and adverse events at the following time points after the intervention: 4 days, 7 days, 3 weeks, 6 weeks, 12 weeks and 16 weeks. All recurrences of CDI symptoms will be investigated with C. difficile laboratory testing to confirm the etiology of these symptoms.
Analysis will be intention to treat. An interim analysis may take place after completion of follow-up of 30 patients. This interim analysis is meant to establish the safety and feasibility of the study, not measure efficacy. Although there were no formal sample size calculations to assess safety of the procedure, with a sample size of 70 participants, an adverse event rate, for example of 2.5%, can be detected with a probability of 0.83 for the fecal transplantation group.
- Conditions
- Recurrent Clostridium Difficile Infection, Laboratory Confirmed Clostridium Difficile Infection
- Being tested
- Vancomycin, Fecal Transplant
- Keywords
- Clostridium difficile, Fecal Transplant, Recurrent Diarrhea, Abdominal distension/bloating, Fever
- Medical subject headings
- Clostridium Infections, Diarrhea, Fever
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VancomycinDrug
Oral Vancomycin:
Dose: 125 mg po qid x 2 weeks then 125 mg po bid x 1 week then 125 mg po od x 1 week then 125 mg po q every other day x 1 week then 125 mg po q every third day x 1 week then discontinue Route: oral
Fecal TransplantBiological
Fecal slurry 50 grams stool in 500ml normal saline
| Study group | Role | What they receive |
|---|---|---|
| Fecal Transplant | Experimental | 2 weeks of oral vancomycin pre-treatment followed by single dose fecal transplant administered by rectal enema. Fecal transplant (slurry) consists of 50 grams healthy donor stool blended in 500ml of Normal Saline. Receives: Biological: Fecal Transplant |
| Oral Vancomycin Taper | Active comparator | 2 weeks of oral vancomycin pre-treatment followed by 6-week taper of oral vancomycin Receives: Drug: Vancomycin |
What is being measured
The primary outcome is the main question the study is designed to answer.
A Randomized Controlled Trial of Oral Vancomycin Followed by Fecal Transplantation versus Tapering Oral Vancomycin Treatment for Recurrent Clostridium difficile Infection.
To assess the number of patients with recurrence of laboratory-confirmed CDI in the 120 days following completion of intervention with either oral vancomycin followed by fecal transplantation or a 6-week taper of oral vancomycin.
Measured: 3 years
Secondary outcomes (1)
A Randomized Controlled Trial of Oral Vancomycin Followed by Fecal Transplantation versus Tapering Oral Vancomycin Treatment for Recurrent Clostridium difficile Infection.
To evaluate the safety profile of fecal transplantation.
To characterize other outcomes of patients treated with fecal transplantation and oral vancomycin, as determined by the following:
- Early (within 14 days of treatment completion) and late (within 120 days of treatment) recurrence of symptoms compatible with CDI; ii. Days with diarrhea in the 120 days post-treatment; iii. CDI requiring hospital admission in the 120 days after treatment onset; iv. All-cause and CDI-attributable mortality; v. Recurrence of CDI in the 120 days after crossover to the alternate treatment arm.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Oct 2010 (estimated)
- Study startOct 2010
- Primary completionOct 2014
- Study completionOct 2014
Why it stopped: Unavailable study resources
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Recurrent Clostridium Difficile InfectionStudies of the same condition, open and under way.
- More trials run by University Health Network, TorontoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 81 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Susy Hota, MD FRCPC, Principal investigator, Infectious Disease, Infection Prevention and Control, EpidemiologistSusan Poutanen, MD MPH FRCPC, Study director, Infectious Disease, Microbiologist
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01226992
- Sponsor's protocol ID
- UHN # 08-0440
- Other IDs
- 9424-U0288/2-25C 124081
- Status last verified
- Oct 2014
- First submitted
- 20 Oct 2010
- Last updated
- 8 Dec 2014
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Hota SS, Sales V, Tomlinson G, Salpeter MJ, McGeer A, Coburn B, Guttman DS, Low DE, Poutanen SM. Oral Vancomycin Followed by Fecal Transplantation Versus Tapering Oral Vancomycin Treatment for Recurrent Clostridium difficile Infection: An Open-Label, Randomized Controlled Trial. Clin Infect Dis. 2017 Feb 1;64(3):265-271. doi: 10.1093/cid/ciw731. Epub 2016 Nov 9.
PubMed 28011612
Study at a glance
From the registry record, last updated by the sponsor on 8 Dec 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II/III Randomized Controlled Trial of Oral Vancomycin Followed by Fecal Transplantation Versus Tapering Oral Vancomycin for Recurrent Clostridium Difficile Infection (CDI)
- ClinicalTrials.gov ID
- NCT01226992
- Acronym / sponsor ID
- UHN # 08-0440
- Conditions
- Recurrent Clostridium Difficile Infection, Laboratory Confirmed Clostridium Difficile Infection
- Keywords
- Clostridium difficile, Fecal Transplant, Recurrent Diarrhea, Abdominal distension/bloating, Fever
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Unavailable study resources
- Enrolment
- 81 participants (actual)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Study start
- Oct 2010
- Primary completion
- Oct 2014 (actual)
- Study completion
- Oct 2014 (actual)
- First posted
- 22 Oct 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Recurrent CDI is a growing problem with few treatment options that provide lasting effect. Fecal transplantation has been shown in several case series to be successful in controlling recurrent CDI. The current study is a non-blinded, randomized controlled trial comparing fecal transplantation with a 6 week taper of oral vancomycin for the treatment of refractory CDI. Approximately 146 patients will be enrolled over one year. Participants in the study will be followed for 120 days, and will be given the opportunity to cross over to the alternative intervention arm if a relapse in symptoms occurs. The primary outcome measure will be recurrence of toxin-confirmed CDI within 120 days of starting the intervention. Secondary outcomes include: early recurrence of symptoms within 14 days, relapse within 120 days (same strain of C. difficile), attributable mortality, hospitalization and serious adverse events.
Detailed description
The proposed trial is a single-centre, phase II/III, open, parallel-group, randomized controlled trial. To have an evaluable population of 114 participants and assuming a 20% loss to follow-up, approximately 146 patients will be randomized in a 1:1 ratio to receive either approximately 2 weeks of oral vancomycin followed by a single fecal transplant via enema (hereon referred to as the "fecal transplant arm") or a 6-week taper of oral vancomycin (hereon referred to as the "vancomycin taper arm"). The 2 weeks of vancomycin pre-treatment in the fecal transplant arm will allow for a fecal transplant donor to be screened for potentially transmissible infectious diseases (clinically and through blood and stool tests), in order to ensure appropriateness and safety of donation.
If patients fail treatment during the follow-up period of 120 days, they will be offered the opportunity to cross over to the alternate treatment arm. Those who cross over will be followed for an additional 120 days from the second intervention.
Participants will be assessed clinically for recurrence in CDI symptoms and adverse events at the following time points after the intervention: 4 days, 7 days, 3 weeks, 6 weeks, 12 weeks and 16 weeks. All recurrences of CDI symptoms will be investigated with C. difficile laboratory testing to confirm the etiology of these symptoms.
Analysis will be intention to treat. An interim analysis may take place after completion of follow-up of 30 patients. This interim analysis is meant to establish the safety and feasibility of the study, not measure efficacy. Although there were no formal sample size calculations to assess safety of the procedure, with a sample size of 70 participants, an adverse event rate, for example of 2.5%, can be detected with a probability of 0.83 for the fecal transplantation group.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Fecal Transplant | Experimental | Biological: Fecal Transplant2 weeks of oral vancomycin pre-treatment followed by single dose fecal transplant administered by rectal enema. Fecal transplant (slurry) consists of 50 grams healthy donor stool blended in 500ml of Normal Saline. |
| Oral Vancomycin Taper | Active comparator | Drug: Vancomycin2 weeks of oral vancomycin pre-treatment followed by 6-week taper of oral vancomycin |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Laboratory or pathology-confirmed diagnosis of recurrent C. difficile infection (CDI) with symptoms within the previous 60 days. Recurrent CDI is defined as:
- Diarrhea (see below) OR
- Abdominal pain AND abdominal distension/bloating AND fever, systemic illness with no other reason for these symptoms
- at least 6 watery feces in 36 hours OR
- 3 unformed feces in 24 hours for minimum 2 days OR
Key exclusion criteria (21 listed)
- Planned participation in another clinical trial
- Patients with conditions such as neutropenia, graft versus host disease or severe immunocompromise, in whom enemas are contraindicated
- More than one episode of CDI that has been severe or rapid in onset, resulting in:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VancomycinOral Vancomycin: Dose: 125 mg po qid x 2 weeks then 125 mg po bid x 1 week then 125 mg po od x 1 week then 125 mg po q every other day x 1 week then 125 mg po q every third day x 1 week then discontinue Route: oral | Drug | Oral Vancomycin Taper |
| Fecal TransplantFecal slurry 50 grams stool in 500ml normal saline | Biological | Fecal Transplant |
Primary outcome
A Randomized Controlled Trial of Oral Vancomycin Followed by Fecal Transplantation versus Tapering Oral Vancomycin Treatment for Recurrent Clostridium difficile Infection.
Time frame: 3 years
To assess the number of patients with recurrence of laboratory-confirmed CDI in the 120 days following completion of intervention with either oral vancomycin followed by fecal transplantation or a 6-week taper of oral vancomycin.
1 secondary outcome
A Randomized Controlled Trial of Oral Vancomycin Followed by Fecal Transplantation versus Tapering Oral Vancomycin Treatment for Recurrent Clostridium difficile Infection.
Time frame: 3 years
Results and safety
The study was stopped early (reason given: Unavailable study resources). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Dec 2014.
- Derived from this study: PubMed 28011612Hota SS, Sales V, Tomlinson G, Salpeter MJ, McGeer A, Coburn B, Guttman DS, Low DE, Poutanen SM. Oral Vancomycin Followed by Fecal Transplantation Versus Tapering Oral Vancomycin Treatment for Recurrent Clostridium difficile Infection: An Open-Label, Randomized Controlled Trial. Clin Infect Dis. 2017 Feb 1;64(3):265-271. doi: 10.1093/cid/ciw731. Epub 2016 Nov 9.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Susy Hota, MD FRCPC principal investigator
Infectious Disease, Infection Prevention and Control, Epidemiologist
Susan Poutanen, MD MPH FRCPC study director
Infectious Disease, Microbiologist
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Vancomycin and Fecal Transplant in people with Recurrent Clostridium Difficile Infection and Laboratory Confirmed Clostridium Difficile Infection, run by University Health Network, Toronto at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 8 Dec 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Unavailable study resources). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
A Randomized Controlled Trial of Oral Vancomycin Followed by Fecal Transplantation versus Tapering Oral Vancomycin Treatment for Recurrent Clostridium difficile Infection. (time frame: 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01226992, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Dec 2014.