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. 2023 Apr 25;2023(4):CD013871. doi: 10.1002/14651858.CD013871.pub2

NCT05077085.

Study name Bezlotoxumab versus FMT for multiple recurrent CDI (BSTEP)
Methods Open‐label, randomized controlled trial
Participants Inclusion criteria

  1. Age 18–90 years

  2. Diarrhea (≥ 3 unformed stools per 24 hours for 2 consecutive days; or ≥ 8 unformed stools per 48 hours)

  3. Positive PCR test for toxin A/B genes or positive toxin EIA for current and previous episodes (or both) (low PCR cycle threshold value when only PCR performed)

  4. Minimum of 2 prior CDI episodes

  5. Previous episode was maximum of 3 months prior to the current episode

  6. Current episode responds well to standard of care treatment (vancomycin or fidaxomicin orally)

  7. Assessment of severity of the disease will be performed according to the ESCMID recommendations

  8. Both mild and severe CDI will be included


Exclusion criteria

  1. Severe complicated CDI, i.e. presence of: hypotension, septic shock, elevated serum lactate, ileus, toxic megacolon, bowel perforation, or any fulminant course of disease

  2. ICU admission for underlying disease

  3. Pregnancy or current desire for pregnancy

  4. Breastfeeding

  5. (Prolonged) use of antibiotics (other than for treatment of CDI) during the study period or directly after the intervention

  6. Previous use of bezlotoxumab or FMT

  7. History of underlying congestive heart failure (potential safety signal phase‐III trial bezlotoxumab)

  8. Diagnosis of inflammatory bowel disease in medical history
Interventions Intervention

  1. Initial bezlotoxumab plus standard of care (14 days of vancomycin 125 mg 4 time per day plus fecal microbiota in case of treatment failure


Comparator

  1. FMT plus standard of care (14 days of vancomycin 125 mg 4 times per day) plus fidaxomicin 200 mg twice daily for 10 days in case of treatment failure
Outcomes Primary outcomes

  1. Global cure of the treatment strategy. Defined as cure without relapse of CDI within 12 weeks after completion of the treatment strategy in the study arm, i.e. after completion of secondary treatment in case of failure on initial treatment (time frame: 12 weeks (after rescue therapy if applicable))


Secondary outcomes

  1. Initial cure after treatment with bezlotoxumab or FMT defined as cure after completion of the primary CDI treatment in the study arm. Initial cure assessed at day 2 after end of treatment (time frame: 2 days after end of treatment)

  2. Recurrence after initial treatment with bezlotoxumab or FMT defined as CDI relapse within 12 weeks after initial cure (time frame: 12 weeks)

  3. Sustained cure after initial treatment with bezlotoxumab or FMT defined as cure without relapse of CDI within 12 weeks after completion of the initial treatment (time frame: 12 weeks)

  4. AEs. Throughout the entire study all AEs will be noted. After the final study procedure of the last patient, all AEs will be categorized:

    1. most likely related to ancillary CDI treatment (bezlotoxumab or FMT)

    2. may be related to ancillary CDI treatment

    3. not related to ancillary CDI treatment (time frame: 12 weeks)

  5. Post‐treatment irritable bowel syndrome‐like symptoms (time frame: 12 weeks)

  6. Duration of hospitalization (time frame: 12 weeks)

  7. Rate of antibiotic use (time frame: 12 weeks)

  8. Eradication of toxigenic C difficile assessed using PCR (time frame: 3 and 12 weeks)

  9. Fecal microbiota (16S) alfa‐ and beta‐diversity assessed using 16S rRNA amplicon sequencing (time frame: pretreatment and 3 and 12 weeks)

  10. Cost‐effectiveness. Costs per cured participant (global and sustained cure) and costs per quality‐adjusted life year gained, using the EQ‐5D‐5L health questionnaire that assesses 5 domains using a 5‐point scale, e.g. no/slight/moderate/severe/extreme impairment and a visual analogue 0–100 scale of health rating, higher is better) (time frame: 12 weeks)


Other outcomes

  1. Participant well‐being. As assessed using a questionnaire, that includes:

    1. self‐rated health – 5‐point scale, higher is worse outcome

    2. happiness – 7‐point scale, higher is worse outcome

    3. optimism – 6 items

    4. 9‐item Patient Health Questionnaire – 9 items with 4‐point scale, higher is worse outcome

    5. Hospital Anxiety and Depression Scale – 14 items (time frame: pretreatment and 12 weeks)

  2. Rate of participants with improved defecation pattern assessed using personal diary (time frame: 12 weeks)
Starting date October 2021
Contact information Joffrey van Prehn MD, PhD, Clinical Microbiologist, Leiden University Medical Center
Notes No results posted