Clostridium DifficilePhase 2NCT03760484
Fecal Microbiota Transplant (FMT) Plus Fidaxomicin for Severe or Fulminant Clostridium Difficile Infection
A Phase 2 study testing Fidaxomicin 200 mg and fecal microbiota transplantation (FMT) in people with Clostridium Difficile, run by University of Alberta at 1 site in Canada.
Trial summary
Fecal microbiota transplantation (FMT) has been very effective for patients who suffer from mild C diff infection (CDI) which recurs but it is unclear how effective FMT alone is in treating severe and fulminant CDI. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Clostridium Difficile
- What is being tested?
- Fidaxomicin 200 mg and fecal microbiota transplantation (FMT)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 1 siteCanada
- Study dates
- 21 Jan 2019to 10 Mar 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age > 18 years with severe1 or fulminant2 CDI, without an adequate response to metronidazole IV 500 mg q8H and vancomycin 500 mg PO q6h for at least 2 days or after Fecal Microbiota Transplant (FMT). An adequate response is defined as a decrease in stool frequency or inflammatory markers (WBC or C reactive protein) by 10% over 48 hours
- Those with ability to provide informed consent or an alternative decision maker providing assent
Who cannot join
- Those with bowel perforation
- Those taking chemotherapy or radiation treatment with absolute neutrophil count of < 1000 cells/mm3
- Those with known colonic strictures
- Those with subtotal colectomy or planning to have a colectomy
- Those with significant ileus
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Serial Fecal Microbiota Transplant (FMT) Plus Fidaxomicin in the Treatment of Severe or Fulminant Clostridium Difficile Infection, With Detailed Characterization in Microbiota, Metabolomics and Host Immune Response
Fecal microbiota transplantation (FMT) has been very effective for patients who suffer from mild C diff infection (CDI) which recurs but it is unclear how effective FMT alone is in treating severe and fulminant CDI. Current evidence suggests that FMT in combination with vancomycin is required, and that multiple treatments are necessary. The investigators think fidaxomicin may be a better option in the context and may potentially reduce the number of FMT required. However, fidaxomicin has never been used to treat severe or fulminant CDI. In this pilot study, the investigators plan to use a combination of FMT plus fidaxomicin to determine efficacy and safety in treating patients with severe or fulminant CDI. The investigators want to see if this approach may reduce the number of FMT treatment required, and/or the length of hospital stay.
Read the detailed description
In this prospective, open -label, multi--center feasibility study, the investigators aim to determine the efficacy and safety of using combined serial FMT by enema plus fidaxomicin to treat patients who have severe or fulminant CDI not responding to maximal medical therapy. The hypothesis is the combination of FMT plus fidaxomicin can reduce the number of FMT required and/or hospital length of stay compared to FMT plus vancomycin.
Participants will receive FMT by enemas over 3 days which constitutes a single cycle with concurrent treatment with oral fidaxomicin. If participants do not show improvement biochemically or clinically, then a repeat FMT cycle will be administered to a maximum of 4 cycles.
- Conditions
- Clostridium Difficile
- Being tested
- Fidaxomicin 200 mg, fecal microbiota transplantation (FMT)
- Keywords
- Fecal microbiota transplantation, Fidaxomicin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fidaxomicin 200 mgDrug
Also called dificid
Each cycle consists of fidaxomicin 200 mg PO bid x 7-10 days till clinical efficacy is achieved, to a max of 4 cycles.
fecal microbiota transplantation (FMT)Biological
Also called biotherapy
Each cycle consists of FMT per rectum daily x 3 days till clinical efficacy is achieved to a max of 4 cycles
| Study group | Role | What they receive |
|---|---|---|
| fecal transplant with fidaxomicin | Experimental | FMT per rectum x 3 days in conjunction with fidaxomicin (dificid) PO 200 mg bid x 7-10 days Receives: Drug: Fidaxomicin 200 mg; Biological: fecal microbiota transplantation (FMT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
C Difficile Infection (CDI) Resolution- Short Term (Two Weeks After Final Fecal Microbiota Transplant (FMT))
Defined as <3 unformed bowel movements/24h or return to baseline bowel habit 2 weeks after final Fecal Microbiota Transplant (FMT)
Measured: 2 weeks after final Fecal Microbiota Transplant (FMT)
Secondary outcomes (6)
Sustained C Difficile Infection (CDI) Resolution (Eight Weeks After Final After Final Fecal Microbiota Transplant (FMT))
Sustained C difficile infection (CDI) resolution defined as lack of C difficile infection (CDI) recurrence 8 weeks after final Fecal Microbiota Transplant (FMT)
Measured: 8 weeks after final Fecal Microbiota Transplant (FMT)
Death
Reported death
Measured: 8 weeks after final Fecal Microbiota Transplant (FMT); up to 96 days
Perforation
Colonic perforation
Measured: 8 weeks after final Fecal Microbiota Transplant (FMT); up to 96 days
Infection
Proven infection related final Fecal Microbiota Transplant (FMT)
Measured: 8 weeks after final Fecal Microbiota Transplant (FMT); up to 96 days.
Hospitalization
Hospitalization due to C. difficile infection (CDI)
Measured: 8 weeks after final Fecal Microbiota Transplant (FMT); up to 96 days.
Colectomy
Surgical Intervention - Colectomy
Measured: 8 weeks after final Fecal Microbiota Transplant (FMT); up to 96 days.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Nov 2018
- Study start21 Jan 2019
- Primary completion10 Mar 2020
- Study completion10 Mar 2020
Why it stopped: Difficulty enrolling participants/COVID pandemic/lack of continued in-kind support from product manufacturer.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Clostridium DifficileStudies of the same condition, open and under way.
- More trials run by University of AlbertaThe 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Alberta
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Dina Kao, MD, Principal investigator, University of Alberta
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03760484
- Sponsor's protocol ID
- Pro00081229
- Status last verified
- Oct 2022
- First submitted
- 15 Nov 2018
- Last updated
- 13 Dec 2022
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Monaghan TM, Duggal NA, Rosati E, Griffin R, Hughes J, Roach B, Yang DY, Wang C, Wong K, Saxinger L, Pucic-Bakovic M, Vuckovic F, Klicek F, Lauc G, Tighe P, Mullish BH, Blanco JM, McDonald JAK, Marchesi JR, Xue N, Dottorini T, Acharjee A, Franke A, Li Y, Wong GK, Polytarchou C, Yau TO, Christodoulou N, Hatziapostolou M, Wang M, Russell LA, Kao DH. A Multi-Factorial Observational Study on Sequential Fecal Microbiota Transplant in Patients with Medically Refractory Clostridioides difficile Infection. Cells. 2021 Nov 19;10(11):3234. doi: 10.3390/cells10113234.
PubMed 34831456
Study at a glance
From the registry record, last updated by the sponsor on 13 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Serial Fecal Microbiota Transplant (FMT) Plus Fidaxomicin in the Treatment of Severe or Fulminant Clostridium Difficile Infection, With Detailed Characterization in Microbiota, Metabolomics and Host Immune Response
- ClinicalTrials.gov ID
- NCT03760484
- Acronym / sponsor ID
- Pro00081229
- Conditions
- Clostridium Difficile
- Keywords
- Fecal microbiota transplantation, Fidaxomicin
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Difficulty enrolling participants/COVID pandemic/lack of continued in-kind support from product manufacturer.
- Enrolment
- 4 participants (actual)
- Lead sponsor
- University of AlbertaUniversity, hospital or other
- Study start
- 21 Jan 2019 (actual)
- Primary completion
- 10 Mar 2020 (actual)
- Study completion
- 10 Mar 2020 (actual)
- First posted
- 30 Nov 2018 (actual)
- Results
- Posted 13 Dec 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Fecal microbiota transplantation (FMT) has been very effective for patients who suffer from mild C diff infection (CDI) which recurs but it is unclear how effective FMT alone is in treating severe and fulminant CDI. Current evidence suggests that FMT in combination with vancomycin is required, and that multiple treatments are necessary. The investigators think fidaxomicin may be a better option in the context and may potentially reduce the number of FMT required. However, fidaxomicin has never been used to treat severe or fulminant CDI. In this pilot study, the investigators plan to use a combination of FMT plus fidaxomicin to determine efficacy and safety in treating patients with severe or fulminant CDI. The investigators want to see if this approach may reduce the number of FMT treatment required, and/or the length of hospital stay.
Detailed description
In this prospective, open -label, multi--center feasibility study, the investigators aim to determine the efficacy and safety of using combined serial FMT by enema plus fidaxomicin to treat patients who have severe or fulminant CDI not responding to maximal medical therapy. The hypothesis is the combination of FMT plus fidaxomicin can reduce the number of FMT required and/or hospital length of stay compared to FMT plus vancomycin.
Participants will receive FMT by enemas over 3 days which constitutes a single cycle with concurrent treatment with oral fidaxomicin. If participants do not show improvement biochemically or clinically, then a repeat FMT cycle will be administered to a maximum of 4 cycles.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| fecal transplant with fidaxomicin | Experimental | Drug: Fidaxomicin 200 mg, Biological: fecal microbiota transplantation (FMT)FMT per rectum x 3 days in conjunction with fidaxomicin (dificid) PO 200 mg bid x 7-10 days |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Age > 18 years with severe1 or fulminant2 CDI, without an adequate response to metronidazole IV 500 mg q8H and vancomycin 500 mg PO q6h for at least 2 days or after Fecal Microbiota Transplant (FMT). An adequate response is defined as a decrease in stool frequency or inflammatory markers (WBC or C reactive protein) by 10% over 48 hours
- Those with ability to provide informed consent or an alternative decision maker providing assent
Key exclusion criteria (5 listed)
- Those with bowel perforation
- Those taking chemotherapy or radiation treatment with absolute neutrophil count of < 1000 cells/mm3
- Those with known colonic strictures
- Those with subtotal colectomy or planning to have a colectomy
- Those with significant ileus
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 |
|---|---|---|
| Fidaxomicin 200 mgAlso: dificidEach cycle consists of fidaxomicin 200 mg PO bid x 7-10 days till clinical efficacy is achieved, to a max of 4 cycles. | Drug | fecal transplant with fidaxomicin |
| fecal microbiota transplantation (FMT)Also: biotherapyEach cycle consists of FMT per rectum daily x 3 days till clinical efficacy is achieved to a max of 4 cycles | Biological | fecal transplant with fidaxomicin |
Primary outcome
C Difficile Infection (CDI) Resolution- Short Term (Two Weeks After Final Fecal Microbiota Transplant (FMT))
Time frame: 2 weeks after final Fecal Microbiota Transplant (FMT)
Defined as <3 unformed bowel movements/24h or return to baseline bowel habit 2 weeks after final Fecal Microbiota Transplant (FMT)
6 secondary outcomes
Sustained C Difficile Infection (CDI) Resolution (Eight Weeks After Final After Final Fecal Microbiota Transplant (FMT))
Time frame: 8 weeks after final Fecal Microbiota Transplant (FMT)
Death
Time frame: 8 weeks after final Fecal Microbiota Transplant (FMT); up to 96 days
Perforation
Time frame: 8 weeks after final Fecal Microbiota Transplant (FMT); up to 96 days
Infection
Time frame: 8 weeks after final Fecal Microbiota Transplant (FMT); up to 96 days.
Hospitalization
Time frame: 8 weeks after final Fecal Microbiota Transplant (FMT); up to 96 days.
Colectomy
Time frame: 8 weeks after final Fecal Microbiota Transplant (FMT); up to 96 days.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Dec 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 34831456Monaghan TM, Duggal NA, Rosati E, Griffin R, Hughes J, Roach B, Yang DY, Wang C, Wong K, Saxinger L, Pucic-Bakovic M, Vuckovic F, Klicek F, Lauc G, Tighe P, Mullish BH, Blanco JM, McDonald JAK, Marchesi JR, Xue N, Dottorini T, Acharjee A, Franke A, Li Y, Wong GK, Polytarchou C, Yau TO, Christodoulou N, Hatziapostolou M, Wang M, Russell LA, Kao DH. A Multi-Factorial Observational Study on Sequential Fecal Microbiota Transplant in Patients with Medically Refractory Clostridioides difficile Infection. Cells. 2021 Nov 19;10(11):3234. doi: 10.3390/cells10113234.
- Individual participant dataSharing planned: No
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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.
Dina Kao, MD principal investigator
University of Alberta
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Fidaxomicin 200 mg and fecal microbiota transplantation (FMT) in people with Clostridium Difficile, run by University of Alberta 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 2 inclusion and 5 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 13 Dec 2022. 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Dec 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
C Difficile Infection (CDI) Resolution- Short Term (Two Weeks After Final Fecal Microbiota Transplant (FMT)) (time frame: 2 weeks after final Fecal Microbiota Transplant (FMT)). 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 NCT03760484, 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 13 Dec 2022.