NCT03548051.

Methods	Multicenter, randomized, placebo‐controlled, partially blinded trial
Participants	Inclusion criteria Providing permission to access medical records Men or non‐pregnant women aged ≥ 18 years at time of enrollment Able to provide signed and dated informed consent ≥ 2 episodes of CDAD in past 12 months, including the last episode if present at screening (defined by ≥ 1 confirmed positive CDAD by diagnostic methods and another occurrence substantiated by medical history) Completed treatment course of ≥ 10 days of oral vancomycin, oral/intravenous metronidazole, or oral fidaxomicin for the most recent episode prior to enrollment Controlled diarrheal symptoms (< 3 unformed stools per 24 consecutive hour period) Deemed likely to survive for 1 year after enrollment Women of childbearing potential in sexual relationships with men must use an acceptable method of birth control from 30 days prior to enrollment until 4 weeks after completing study treatment Men must agree to avoid impregnation of women between day 1 and day 28 following each administration of study product Negative urine or serum pregnancy test within 24 hours of enrollment and randomization Able to provide blood and fecal specimens Able to complete a test of comprehension Exclusion criteria FMT within the previous 12 months prior to study enrollment Any heart, lung, pancreas, or intestinal transplant recipient or any HIV positive‐transplant recipient Requiring antibiotics in past 2 weeks prior to receiving the enema for a condition other than CDAD or scheduled to be used in the upcoming 2 weeks Unable to tolerate enema for any reason Any GI cancer in past 6 months or any actively treated malignancy, except those actively treated for basal and squamous cell cancers without any systemic treatment History of severe anaphylactic food allergy People with decompensated cirrhosis, untreated HIV disease or other severe immunosuppression or immunodeficiency conditions Severe or acute disease at time of enrollment Major surgery of the GI tract in past 2 months Non‐tolerance to or any component of vancomycin, loperamide, or polyethylene glycol Active inflammatory bowel disease including ulcerative colitis, Crohn disease, indeterminate colitis, or celiac disease Uncontrolled irritable bowel syndrome or any active uncontrolled GI disorders or diseases Unable to comply with protocol requirements. Participation in any other clinical drug research trial within 30 days prior to enrollment or for 1 year after enrollment that might interfere with the safety and efficacy assessment A condition that would jeopardize the safety or rights of the person, would make it unlikely for the person to complete the study, or would confound the results of the study
Interventions	Intervention 100 g of thawed processed stool diluted into 250 mL of saline and delivered by retention enema given 1–3 hours after loperamide 4 mg orally × 1 Comparison 250 mL of saline delivered by retention enema given 1–3 hours after loperamide 4 mg orally × 1
Outcomes	Primary outcomes New‐onset related chronic medical condition after completing treatment for recurrent CDAD (time frame: up to 365 days) SAEs (assessed using Adverse Event Grading Scale) after completing treatment for recurrent CDAD (time frame: up to 365 days) AEs (assessed using Adverse Event Grading Scale) after completing treatment for recurrent CDAD (time frame: up to 30 days) Newly acquired transmissible infectious diseases that are considered Adverse Event of Special Interest, after completing treatment for recurrent CDAD (time frame: up to 365 days) Clinical response (defined as no recurrence of CDAD) (time frame: up to 30 days) Secondary outcomes Number of recurrences of CDAD after completing treatment for recurrent CDAD (time frame: up to 30 days and 60 days) Sustained clinical response (time frame: up to 60 days) Time to first CDAD recurrence (time frame: up to 60 days)
Notes	Terminated (low enrollment)

CDAD: Clostridioides difficile‐associated diarrhea; CDI: Clostridioides difficile infection; EIA: enzyme immunoassay; FMT: fecal microbiota transplantation; PCR: polymerase chain reaction; rCDI: recurrent Clostridioides difficile infection.