A Phase 2/3 interventional study of Fecal Microbiota Therapy (FMT) and Placebo in Clostridium Difficile Infection, sponsored by VA Office of Research and Development. Terminated at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-04-11.
Sponsored by VA Office of Research and Development · Phase 2/3, Interventional, and Prevention
The purpose of this study is to determine whether Fecal Microbiota Therapy (FMT) is effective vs. placebo in the prevention of C. difficile infection recurrence.
Clostridium difficile infection (CDI) is one of the most common nosocomial infections and is increasingly seen in non-hospitalized patients. Although more than 90% of patients have symptom resolution with a course of standard antimicrobial therapy, subsequent recurrence rates range from 15-30% (after the first CDI episode) to 40-50% (after the second and subsequent episodes). Fecal microbiota transplantation (FMT) has shown promise as an adjunct to standard antimicrobial therapy, reducing recurrence among FMT recipients to 15%.
The primary study goal is to assess the efficacy of FMT for the prevention of subsequent recurrent CDI, when administered after successful treatment of recurrent CDI with standard antimicrobial therapy. Secondary goals are to evaluate, the efficacy of FMT in terms of CDI severity, duration, the safety of FMT, and in the event of a positive study result, establish a mechanism for providing FMT within the VA system.
This study will enroll 390 participants. Participants will be randomized (1:1 ratio) to FMT or placebo, stratified by number of prior recurrent CDI episodes (1 versus >1). They will be assessed for symptoms of CDI, other study outcomes and any treatment-related adverse events at 2, 14, 28, 42, and 56 days, and month 3, 4, 5 and 6 after administration of the study treatment.
The primary outcome is recurrent CDI (definite or possible) or death within 56 days of randomization.
Definite recurrence is defined as any of the following: The new onset of more than three loose or watery stools in 24 hours for two consecutive days, not explained by another diagnosis; Other clinical symptoms including ileus, toxic megacolon, or colectomy; plus laboratory confirmation of C. difficile from a stool specimen by toxin Enzyme Immunoassays (EIA) test. Possible recurrence is defined as the same clinical manifestations as above, but without laboratory confirmation of C. difficile (stool test not sent, negative EIA toxin test result, or uninterpretable result).
310 studies on the registry are indexed under Clostridium Infections; 50 are open to participants now.
This study's enrollment of 153 is above the median of 65 across 233 interventional studies indexed under Clostridium Infections.
Browse Clostridium Infections studies →VA Office of Research and Development is the lead sponsor of 1,733 studies on the registry; 396 are open to participants now.
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Exclusion Criteria:
Fecal Microbiota Therapy (FMT)
Drug: Fecal Microbiota Therapy (FMT)
Placebo
Drug: Placebo
Oral capsule-delivered FMT
Oral capsule-delivered placebo
Possible or Definite Recurrent Clostridium Difficile Infection (CDI), or Death
The primary outcome is recurrent CDI (definite or possible) or death within 56 days of randomization. A possible CDI recurrence is defined as a new onset of more than three loose or watery stools in 24 hours for two consecutive days, not explained by another diagnosis, other clinical symptoms including ileus, toxic megacolon, or colectomy. As part of the protocol procedures, a possible CDI recurrence is adjudicated by the study's adjudication committee. A definite CDI recurrence is defined as a potential CDI recurrence with symptom (more than three loose or watery stools in 24 hours for two consecutive days, not explained by another diagnosis, other clinical symptoms including ileus, toxic megacolon, or colectomy) plus laboratory confirmation of C. difficile from a stool specimen by toxin Enzyme Immunoassays (EIA) test.
Time frame: Within 56 days of randomization
Recurrent CDI (Definite or Possible) or Death Within 6 Months of Randomization.
A possible CDI recurrence is defined as a new onset of more than three loose or watery stools in 24 hours for two consecutive days, not explained by another diagnosis, other clinical symptoms including ileus, toxic megacolon, or colectomy. As part of the protocol procedures, a possible CDI recurrence is adjudicated by the study's adjudication committee. A definite CDI recurrence is defined as a potential CDI recurrence with symptom (more than three loose or watery stools in 24 hours for two consecutive days, not explained by another diagnosis, other clinical symptoms including ileus, toxic megacolon, or colectomy) plus laboratory confirmation of C. difficile from a stool specimen by EIA toxin test.
Time frame: Within 6 months of randomization
Quality of Life at 56 Day
The investigators will use a brief assessment of both overall and gastrointestinal health status, a previously validated instrument called Gastrointestinal Quality of Life Index (GIQLI). GIQLI takes value between 0 and 144, with higher score associated with better quality of life.
Time frame: 56 days from randomization
Frequency of Possible CDI Recurrences Within 6 Months of Randomization
A possible CDI recurrence is defined as a new onset of more than three loose or watery stools in 24 hours for two consecutive days, not explained by another diagnosis, other clinical symptoms including ileus, toxic megacolon, or colectomy. As part of the protocol procedures, a possible CDI recurrence is adjudicated by the study's adjudication committee.
Time frame: Within 6 months of randomization
Diarrhea That is Negative for C. Difficile by EIA Toxin Test and Polymerase Chain Reaction (PCR)
This is similar to a possible recurrent CDI, but includes only episodes of diarrhea that are tested negative for C. difficile by EIA toxin test and PCR. A possible CDI recurrence is defined as a new onset of more than three loose or watery stools in 24 hours for two consecutive days, not explained by another diagnosis, other clinical symptoms including ileus, toxic megacolon, or colectomy. As part of the protocol procedures, a possible CDI recurrence is adjudicated by the study's adjudication committee.
Time frame: Within 56 days of randomization
Occurrence of Abdominal Pain Among All Possible CDI Recurrences.
A possible CDI recurrence is defined as a new onset of more than three loose or watery stools in 24 hours for two consecutive days, not explained by another diagnosis, other clinical symptoms including ileus, toxic megacolon, or colectomy. As part of the protocol procedures, a possible CDI recurrence is adjudicated by the study's adjudication committee. Participants were asked to report whether they experienced abdominal pain in each of their possible CDI recurrences.
Time frame: Within 6 months of randomization
Definite Recurrent CDI
The occurrence of definite recurrent CDI within 56 days of randomization. A definite CDI recurrence is defined as a potential CDI recurrence with symptom (more than three loose or watery stools in 24 hours for two consecutive days, not explained by another diagnosis, other clinical symptoms including ileus, toxic megacolon, or colectomy) plus laboratory confirmation of C. difficile from a stool specimen by EIA toxin test.
Time frame: Within 56 days of randomization
Possible Recurrent CDI
The occurrence of possible recurrent CDI within 56 days of randomization. A possible CDI recurrence is defined as a new onset of more than three loose or watery stools in 24 hours for two consecutive days, not explained by another diagnosis, other clinical symptoms including ileus, toxic megacolon, or colectomy. As part of the protocol procedures, a possible CDI recurrence is adjudicated by the study's adjudication committee.
Time frame: Within 56 days of randomization
Death
The occurrence of death within 56 days of randomization.
Time frame: Within 56 days of randomization
Diarrhea That is Negative for C. Difficile by EIA Toxin Testing But Positive by PCR
This is similar to possible recurrent CDI, but includes only episodes of diarrhea that are tested negative for C. difficile by EIA toxin test but positive by PCR. A possible CDI recurrence is defined as a new onset of more than three loose or watery stools in 24 hours for two consecutive days, not explained by another diagnosis, other clinical symptoms including ileus, toxic megacolon, or colectomy. As part of the protocol procedures, a possible CDI recurrence is adjudicated by the study's adjudication committee.
Time frame: Within 56 days of randomization
Occurrence of Urgency Among All Possible CDI Recurrences.
A possible CDI recurrence is defined as a new onset of more than three loose or watery stools in 24 hours for two consecutive days, not explained by another diagnosis, other clinical symptoms including ileus, toxic megacolon, or colectomy. As part of the protocol procedures, a possible CDI recurrence is adjudicated by the study's adjudication committee. Participants were asked to report whether they experienced urgency in each of their possible CDI recurrences. The urgency is defined as the urgent need to pass stool, feelings of incomplete bowel control, or inability to control defecation.
Time frame: within 6 months from randomization
Occurrence of Fecal Incontinence Among All Possible CDI Recurrences.
A possible CDI recurrence is defined as a new onset of more than three loose or watery stools in 24 hours for two consecutive days, not explained by another diagnosis, other clinical symptoms including ileus, toxic megacolon, or colectomy. As part of the protocol procedures, a possible CDI recurrence is adjudicated by the study's adjudication committee. Participants were asked to report whether they experienced fecal incontinence in each of their possible CDI recurrences. Fecal incontinence is defined as having unintentional passing of stool (liquid or solid).
Time frame: within 6 months from randomization
Occurrence of Altering Life Style Among All Possible CDI Recurrences
A possible CDI recurrence is defined as a new onset of more than three loose or watery stools in 24 hours for two consecutive days, not explained by another diagnosis, other clinical symptoms including ileus, toxic megacolon, or colectomy. As part of the protocol procedures, a possible CDI recurrence is adjudicated by the study's adjudication committee. Participants were asked to report whether they had to alter their life style (such as using pads) in each of the possible CDI recurrence.
Time frame: within 6 months of randomization
| Milestone | Fecal Microbiota Therapy | Placebo |
|---|---|---|
| Started | 76 | 77 |
| Completed | 76 | 76 |
| Not completed | 0 | 1 |
The primary outcome is recurrent CDI (definite or possible) or death within 56 days of randomization. A possible CDI recurrence is defined as a new onset of more than three loose or watery stools in 24 hours for two consecutive days, not explained by another diagnosis, other clinical symptoms including ileus, toxic megacolon, or colectomy. As part of the protocol procedures, a possible CDI recurrence is adjudicated by the study's adjudication committee. A definite CDI recurrence is defined as a potential CDI recurrence with symptom (more than three loose or watery stools in 24 hours for two consecutive days, not explained by another diagnosis, other clinical symptoms including ileus, toxic megacolon, or colectomy) plus laboratory confirmation of C. difficile from a stool specimen by toxin Enzyme Immunoassays (EIA) test.
| Participants | Fecal Microbiota Therapy (FMT) | Placebo |
|---|---|---|
| Possible or Definite Recurrent Clostridium Difficile Infection (CDI), or Death | 25 | 23 |
A possible CDI recurrence is defined as a new onset of more than three loose or watery stools in 24 hours for two consecutive days, not explained by another diagnosis, other clinical symptoms including ileus, toxic megacolon, or colectomy. As part of the protocol procedures, a possible CDI recurrence is adjudicated by the study's adjudication committee. A definite CDI recurrence is defined as a potential CDI recurrence with symptom (more than three loose or watery stools in 24 hours for two consecutive days, not explained by another diagnosis, other clinical symptoms including ileus, toxic megacolon, or colectomy) plus laboratory confirmation of C. difficile from a stool specimen by EIA toxin test.
| Participants | Fecal Microbiota Therapy (FMT) | Placebo |
|---|---|---|
| Recurrent CDI (Definite or Possible) or Death Within 6 Months of Randomization. | 32 | 31 |
The investigators will use a brief assessment of both overall and gastrointestinal health status, a previously validated instrument called Gastrointestinal Quality of Life Index (GIQLI). GIQLI takes value between 0 and 144, with higher score associated with better quality of life.
| units on a scale | Fecal Microbiota Therapy (FMT) | Placebo |
|---|---|---|
| Quality of Life at 56 Day | 111.42 ± 21.25 | 115.67 ± 19.15 |
A possible CDI recurrence is defined as a new onset of more than three loose or watery stools in 24 hours for two consecutive days, not explained by another diagnosis, other clinical symptoms including ileus, toxic megacolon, or colectomy. As part of the protocol procedures, a possible CDI recurrence is adjudicated by the study's adjudication committee.
| Participants | Fecal Microbiota Therapy (FMT) | Placebo |
|---|---|---|
| Have no possible CDI recurrence | 45 | 48 |
| Have one possible CDI recurrence | 23 | 19 |
| Have two possible CDI recurrences | 7 | 9 |
| Have three possible CDI recurrences | 1 | 1 |
This is similar to a possible recurrent CDI, but includes only episodes of diarrhea that are tested negative for C. difficile by EIA toxin test and PCR. A possible CDI recurrence is defined as a new onset of more than three loose or watery stools in 24 hours for two consecutive days, not explained by another diagnosis, other clinical symptoms including ileus, toxic megacolon, or colectomy. As part of the protocol procedures, a possible CDI recurrence is adjudicated by the study's adjudication committee.
| Participants | Fecal Microbiota Therapy | Placebo |
|---|---|---|
| Diarrhea That is Negative for C. Difficile by EIA Toxin Test and Polymerase Chain Reaction (PCR) | 9 | 8 |
A possible CDI recurrence is defined as a new onset of more than three loose or watery stools in 24 hours for two consecutive days, not explained by another diagnosis, other clinical symptoms including ileus, toxic megacolon, or colectomy. As part of the protocol procedures, a possible CDI recurrence is adjudicated by the study's adjudication committee. Participants were asked to report whether they experienced abdominal pain in each of their possible CDI recurrences.
| Recurrences | Fecal Microbiota Therapy | Placebo |
|---|---|---|
| Occurrence of Abdominal Pain Among All Possible CDI Recurrences. | 19 | 24 |
The occurrence of definite recurrent CDI within 56 days of randomization. A definite CDI recurrence is defined as a potential CDI recurrence with symptom (more than three loose or watery stools in 24 hours for two consecutive days, not explained by another diagnosis, other clinical symptoms including ileus, toxic megacolon, or colectomy) plus laboratory confirmation of C. difficile from a stool specimen by EIA toxin test.
| Participants | Fecal Microbiota Therapy | Placebo |
|---|---|---|
| Definite Recurrent CDI | 6 | 7 |
The occurrence of possible recurrent CDI within 56 days of randomization. A possible CDI recurrence is defined as a new onset of more than three loose or watery stools in 24 hours for two consecutive days, not explained by another diagnosis, other clinical symptoms including ileus, toxic megacolon, or colectomy. As part of the protocol procedures, a possible CDI recurrence is adjudicated by the study's adjudication committee.
| Participants | Fecal Microbiota Therapy | Placebo |
|---|---|---|
| Possible Recurrent CDI | 24 | 22 |
The occurrence of death within 56 days of randomization.
| Participants | Fecal Microbiota Therapy | Placebo |
|---|---|---|
| Death | 1 | 1 |
This is similar to possible recurrent CDI, but includes only episodes of diarrhea that are tested negative for C. difficile by EIA toxin test but positive by PCR. A possible CDI recurrence is defined as a new onset of more than three loose or watery stools in 24 hours for two consecutive days, not explained by another diagnosis, other clinical symptoms including ileus, toxic megacolon, or colectomy. As part of the protocol procedures, a possible CDI recurrence is adjudicated by the study's adjudication committee.
| Participants | Fecal Microbiota Therapy (FMT) | Placebo |
|---|---|---|
| Diarrhea That is Negative for C. Difficile by EIA Toxin Testing But Positive by PCR | 6 | 6 |
A possible CDI recurrence is defined as a new onset of more than three loose or watery stools in 24 hours for two consecutive days, not explained by another diagnosis, other clinical symptoms including ileus, toxic megacolon, or colectomy. As part of the protocol procedures, a possible CDI recurrence is adjudicated by the study's adjudication committee. Participants were asked to report whether they experienced urgency in each of their possible CDI recurrences. The urgency is defined as the urgent need to pass stool, feelings of incomplete bowel control, or inability to control defecation.
| Recurrences | Fecal Microbiota Therapy | Placebo |
|---|---|---|
| Occurrence of Urgency Among All Possible CDI Recurrences. | 36 | 36 |
A possible CDI recurrence is defined as a new onset of more than three loose or watery stools in 24 hours for two consecutive days, not explained by another diagnosis, other clinical symptoms including ileus, toxic megacolon, or colectomy. As part of the protocol procedures, a possible CDI recurrence is adjudicated by the study's adjudication committee. Participants were asked to report whether they experienced fecal incontinence in each of their possible CDI recurrences. Fecal incontinence is defined as having unintentional passing of stool (liquid or solid).
| Recurrences | Fecal Microbiota Therapy | Placebo |
|---|---|---|
| Occurrence of Fecal Incontinence Among All Possible CDI Recurrences. | 21 | 18 |
A possible CDI recurrence is defined as a new onset of more than three loose or watery stools in 24 hours for two consecutive days, not explained by another diagnosis, other clinical symptoms including ileus, toxic megacolon, or colectomy. As part of the protocol procedures, a possible CDI recurrence is adjudicated by the study's adjudication committee. Participants were asked to report whether they had to alter their life style (such as using pads) in each of the possible CDI recurrence.
| Recurrences | Fecal Microbiota Therapy | Placebo |
|---|---|---|
| Occurrence of Altering Life Style Among All Possible CDI Recurrences | 30 | 25 |
Collected over All participants will be monitored for adverse events from the time of randomization/ administration of study medication to the study exit time (typically at 6 months after study treatment).. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Fecal Microbiota Therapy (FMT) | 1/76 (1.3%) | 17/76 (22.4%) | 19/76 (25%) |
| Placebo | 5/77 (6.5%) | 21/77 (27.3%) | 28/77 (36.4%) |
| Event | Fecal Microbiota Therapy (FMT) | Placebo |
|---|---|---|
| clostridium difficile infectionInfections and infestations | 2/76 | 6/77 |
| cardiac failureCardiac disorders | 3/76 | 1/77 |
| sepsisInfections and infestations | 2/76 | 1/77 |
| cellulitisInfections and infestations | 2/76 | 0/77 |
| nephrolithiasisRenal and urinary disorders | 2/76 | 0/77 |
| urinary tract infectionInfections and infestations | 1/76 | 2/77 |
| chronic obstructive pulmonary diseaseRespiratory, thoracic and mediastinal disorders | 0/76 | 2/77 |
| Immune thrombocytopeniaBlood and lymphatic system disorders | 1/76 | 0/77 |
| atrioventricular blockCardiac disorders | 1/76 | 0/77 |
| diarrhoeaGastrointestinal disorders | 1/76 | 0/77 |
| Event | Fecal Microbiota Therapy (FMT) | Placebo |
|---|---|---|
| FlatulenceGastrointestinal disorders | 1/76 | 5/77 |
| NauseaGastrointestinal disorders | 4/76 | 4/77 |
| Dafaecation urgencyGastrointestinal disorders | 3/76 | 4/77 |
| constipationGastrointestinal disorders | 3/76 | 3/77 |
| abdominal distensionGastrointestinal disorders | 0/76 | 3/77 |
| diarrhoeaGastrointestinal disorders | 2/76 | 2/77 |
| abdominal painGastrointestinal disorders | 2/76 | 2/77 |
| vomitingGastrointestinal disorders | 2/76 | 2/77 |
| fatiguaGeneral disorders | 2/76 | 0/77 |
| decreased appetiteMetabolism and nutrition disorders | 2/76 | 1/77 |
all participants who were randomized
| Age, Categorical(Participants) | Fecal Microbiota Therapy (FMT) | Placebo | Total |
|---|---|---|---|
| <=18 years | 0 | 0 | 0 |
| Between 18 and 65 years | 20 | 33 | 53 |
| >=65 years | 56 | 44 | 100 |
| Age, Continuous(years) | Fecal Microbiota Therapy (FMT) | Placebo | Total |
|---|---|---|---|
| Mean | 69.2 ± 12.31 | 63.9 ± 14.63 | 66.5 ± 13.74 |
| Sex: Female, Male(Participants) | Fecal Microbiota Therapy (FMT) | Placebo | Total |
|---|---|---|---|
| Female | 8 | 13 | 21 |
| Male | 68 | 64 | 132 |
| Race/Ethnicity, Customized(participants) | Fecal Microbiota Therapy (FMT) | Placebo | Total |
|---|---|---|---|
| Race : White | 70 | 75 | 145 |
| Race : African-American or Black | 6 | 2 | 8 |
| Race : American Indian or Alaska Native | 3 | 0 | 3 |
| Race : Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Race : Chinese | 0 | 0 | 0 |
| Race : Japanese | 0 | 0 | 0 |
| Race : Filipino | 0 | 0 | 0 |
| Race : Asian Indian | 0 | 0 | 0 |
| Race : Other Asian | 0 | 0 | 0 |
| Race : Other Race | 1 | 0 | 1 |
| Region of Enrollment(participants) | Fecal Microbiota Therapy (FMT) | Placebo | Total |
|---|---|---|---|
| United States | 76 | 77 | 153 |
| Albumin(g/dL) | Fecal Microbiota Therapy (FMT) | Placebo | Total |
|---|---|---|---|
| Mean | 3.7 ± 0.6 | 3.9 ± 0.6 | 3.8 ± 0.6 |
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Supporting information: Study protocol, Sap, Icf
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