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NCT03548051

Safety and Efficacy of FMT in Individuals With One or More Recurrences of Clostridium Difficile Associated Disease (CDAD)

Terminated Phase 1, PHASE2 Results posted Last updated 2 May 2022
What this trial tests

Phase 1, PHASE2 trial testing Fecal Microbiota Transplantation (FMT) in Clostridial Infection in 10 participants. Terminated before completion.

Timeline
11 January 2019
Primary endpoint
13 January 2021
13 January 2021

Quick facts

Lead sponsorNational Institute of Allergy and Infectious Diseases (NIAID)
PhasePhase 1, PHASE2
StatusTerminated
Study typeINTERVENTIONAL
Allocationrandomized
Designsequential
Maskingdouble
Primary purposetreatment
Enrollment10
Start date11 January 2019
Primary completion13 January 2021
Estimated completion13 January 2021
Sites3 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Who can join

Adults 18 to 99, any sex, with Clostridial Infection or Dysbiosis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With a New Onset of Related Chronic Medical Condition After Completing Treatment for Recurrent Clostridium Difficile-Associated Diarrhea (CDAD) Primary · Day 1 through Day 365

New onset of related chronic medical conditions (NOCMCs) through 365 days after completing treatment for recurrent CDAD were reported. NOCMCs were defined as any new ICD-10 diagnosis that is applied to the participant during the duration of the study, after receipt of the study agent, that is expected to continue for at least 3 months and requires continued health care intervention.

GroupValue95% CI
FMPE Group0
FMPP Group0
Number of Participants With a Serious Adverse Event (SAE) After Completing Treatment for Recurrent Clostridium Difficile-Associated Diarrhea (CDAD) Primary · Day 1 through Day 365

SAEs included any adverse event or suspected adverse reaction which, in the view of the investigator or sponsor, resulted in any of the following: death, life threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a congenital anomaly/birth defect, persistent or significant disability or incapacity or substantial disruption of the ability to conduct normal life function.

GroupValue95% CI
FMPE Group3
FMPP Group2
Number of Participants With an Adverse Event (AE) After Completing Treatment for Recurrent Clostridium Difficile-Associated Diarrhea (CDAD) Primary · Day 1 through Day 30

Adverse events were defined as any noxious, pathologic, or unintended change in anatomic, physiologic, or metabolic functions, as indicated by physical signs, symptoms, and/or laboratory changes occurring in any phase of the clinical trial, regardless of their relationship to investigational product.

GroupValue95% CI
FMPE Group4
FMPP Group0
Number of Participants With Newly Acquired Transmissible Infectious Diseases Which Are Considered Adverse Events of Special Interest (AESI), After Completing Treatment for Recurrent Clostridium Difficile-Associated Diarrhea (CDAD) Primary · Day 1 through Day 365

Adverse Events of Special Interest were defined as newly acquired transmissible infectious agents or infectious diseases related to study product and the following agents: HIV type 1 and 2, Hepatitis A, B, C, Treponema pallidum, HTLV-1, -2, Cyclospora, Salmonella, Shigella, Campylobacter, E. coli 0157:H7, Shiga-toxin producing E. coli, Ova and enteric parasites including Isospora, Vancomycin-resistant Enterococcus (VRE), extended spectrum beta-lactamase (ESBL), carbapenemase producing gram-negative rods, methicillinresistant Staphylococcus aureus (MRSA), Helicobacter pylori, Rotavirus, Adenovi

GroupValue95% CI
FMPE Group0
FMPP Group0
Proportion of Participants With Clinical Response (Defined as no Recurrence of Clostridium Difficile-Associated Diarrhea (CDAD)) Primary · Day 1 through Day 30

Clinical response was defined as those subjects who have no recurrence of CDAD through Day 30 after completing treatment for recurrent CDAD. CDAD was defined as bowel movements as determined by \>=3 unformed stools (soft or watery) within 24 consecutive hours and a positive PCR test for Clostridium difficile.

GroupValue95% CI
FMPE Group0.800.38 – 0.96
FMPP Group0.750.30 – 0.95
Number of Recurrences of Clostridium Difficile-Associated Diarrhea (CDAD) After Completing Treatment for Recurrent CDAD Secondary · Day 1 through Day 30

Recurrence was defined as the re-establishment of diarrhea (frequency of passed unformed stools, \>=3 unformed stools within 24 consecutive hours) with a positive PCR test for C. difficile.

GroupValue95% CI
FMPE Group0.2± 0.4
FMPP Group0.3± 0.5
Number of Recurrences of Clostridium Difficile-Associated Diarrhea (CDAD) After Completing Treatment for Recurrent CDAD Secondary · Day 1 through Day 60

Recurrence was defined as the re-establishment of diarrhea (frequency of passed unformed stools, \>=3 unformed stools within 24 consecutive hours) with a positive PCR test for C. difficile.

GroupValue95% CI
FMPE Group0.2± 0.4
FMPP Group0.3± 0.5
Proportion of Participants With Sustained Clinical Response Secondary · Day 1 through Day 60

Sustained clinical response is defined as those subjects who responded by Day 30 with no recurrence of CDAD through Day 60 after randomization.

GroupValue95% CI
FMPE Group0.800.38 – 0.96
FMPP Group0.750.30 – 0.95
Time to First Clostridium Difficile-Associated Diarrhea (CDAD) Reoccurrence (Using the Date of First Positive PCR Post-enema) Secondary · Day 1 through Day 60 visit windows reported as Weeks 1 through 8, respectively

The time (in weeks) until first CDAD recurrence was calculated as time from randomization to the end of the interval of ascertainment. Participants without a recurrence were censored at their last known contact date or their Day 60 visit, whichever occurred first.

Week 1 at Risk
GroupValue95% CI
FMPE Group5
FMPP Group4
Week 1 with CDAD
GroupValue95% CI
FMPE Group0
FMPP Group0
Week 1 Censored
GroupValue95% CI
FMPE Group0
FMPP Group0
Week 2 at Risk
GroupValue95% CI
FMPE Group5
FMPP Group4
Week 2 with CDAD
GroupValue95% CI
FMPE Group1
FMPP Group1
Week 2 Censored
GroupValue95% CI
FMPE Group0
FMPP Group0
Week 3 at Risk
GroupValue95% CI
FMPE Group4
FMPP Group3
Week 3 with CDAD
GroupValue95% CI
FMPE Group0
FMPP Group0

Adverse events — posted to ClinicalTrials.gov

Time frame: Solicited AEs were collected through 8 days after each enema. Non-serious AEs and abnormal clinical laboratory tests were collected from treatment initiation through 30 days after completing treatment for recurrent CDAD. SAEs, NOCMCs, AESIs, and new onset metabolic syndrome were collected from treatment initiation through 365 days after completing treatment for recurrent CDAD. All-cause mortality was assessed through 365 days after completing treatment for recurrent CDAD.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

FMPE Group
Serious: 3/6 (50%)
Deaths: 1/6
FMPP Group
Serious: 2/4 (50%)
Deaths: 1/4

Serious adverse events (12 terms)

ReactionSystemFMPE GroupFMPP Group
DiarrhoeaGastrointestinal disorders
Clostridium difficile infectionInfections and infestations
Cerebral HaemorrhageNervous system disorders
PneumoniaInfections and infestations
Abdominal PainGastrointestinal disorders
DehydrationMetabolism and nutrition disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
DysuriaRenal and urinary disorders
COVID-19Infections and infestations
UrosepsisInfections and infestations
SepsisInfections and infestations
OsteomyelitisInfections and infestations
Other adverse events (22 terms — click to expand)

ReactionSystemFMPE GroupFMPP Group
Abdominal DistentionGastrointestinal disorders
Abdominal PainGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
FlatulenceGastrointestinal disorders
MalaiseGeneral disorders
ConstipationGastrointestinal disorders
NauseaGastrointestinal disorders
Decreased AppetiteMetabolism and nutrition disorders
VomitingGastrointestinal disorders
ChillsGeneral disorders
HypertensionVascular disorders
TachycardiaCardiac disorders
PyrexiaGeneral disorders
Diastolic HypertensionVascular disorders
Systolic HypertensionVascular disorders
TachycardiaCardiac disorders
HaemorrhoidsGastrointestinal disorders
NauseaGastrointestinal disorders
OesophagitisGastrointestinal disorders
PyrexiaGeneral disorders
RhinitisInfections and infestations
Blood pressure IncreasedInvestigations

Most-reported serious reactions: Diarrhoea, Clostridium difficile infection, Cerebral Haemorrhage, Pneumonia, Abdominal Pain, Dehydration, Dyspnoea, Dysuria.

Data from ClinicalTrials.gov NCT03548051 adverse events section.

Sponsor's own description

Multi-center, randomized, placebo controlled, partially blinded trial comparing the safety and efficacy of fecal microbiota transplantation versus placebo both delivered by rectal enema in subjects 18 years of age or older with recurrent Clostridium difficile Associated Disease (CDAD). 162 male or female subjects will be enrolled in the study. Enrolled subjects will be randomized at each site to receive either FMT by enema or placebo by enema in a 2:1 ratio. Study duration is 3 years, subject participation duration is approximately 1 year. The primary study objectives are: 1) to evaluate the safety of FMT(s) delivered by enema vs. placebo delivered by enema and 2) to determine efficacy of FMT delivered by enema vs. placebo delivered by enema.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Fecal microbiota transplantation for the treatment of recurrent Clostridioides difficile (Clostridium difficile).
    Minkoff NZ, Aslam S, Medina M, Tanner-Smith EE, et al · · 2023 · cited 82× · PMID 37096495 · DOI 10.1002/14651858.cd013871.pub2
  2. The development of live biotherapeutics against <i>Clostridioides difficile</i> infection towards reconstituting gut microbiota.
    Zhang Y, Saint Fleur A, Feng H. · · 2022 · cited 23× · PMID 35319337 · DOI 10.1080/19490976.2022.2052698

Verify or expand the search:

Other trials of Fecal Microbiota Transplantation (FMT)

Trials testing the same drug.

Other National Institute of Allergy and Infectious Diseases (NIAID) trials

Trials by the same sponsor.

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