Bezlotoxumab Versus FMT for Multiple Recurrent CDI

Browse trials for

• Infections 6,688
• Clostridium Infections 310
• Enterocolitis, Pseudomembranous 29
• Enterocolitis 216

Study arms

• Experimental
  Strategy A: initial SoC + bezlotoxumab. SoC + FMT rescue therapy.

  initial bezlotoxumab in addition to 14 days SoC oral antibiotic treatment with vancomycin 125 mg QID. 14 days of vancomycin 125mg QID plus fecal microbiota in case of treatment failure.

  Drug: Bezlotoxumab · Drug: Vancomycin oral

• Active comparator
  Strategy B: initial SoC + FMT. Fidaxomicin rescue therapy.

  fecal microbiota transplantation in addition to 14 days SoC oral antibiotic treatment with vancomycin 125 mg QID. 10 days of fidaxomicin 200 mg BID in case of treatment failure.

  Procedure: Fecal Microbiota Transplantation (FMT) · Drug: Vancomycin oral

Interventions

• DrugBezlotoxumab

  single intravenous infusion of bezlotoxumab 10 mg/kg

• ProcedureFecal Microbiota Transplantation (FMT)

  single infusion of 198 cc fecal suspension (derived from 60g donor feces) via duodenal tube or coloscopy

• DrugVancomycin oral

  14 days vancomycin oral 125mg QID (250mg QID when 125mg not available)

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 is assessed at day 2 after end of treatment (EOT).

   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

   Sustained cure is defined as cure without relapse of CDI within 12 weeks after completion of the initial treatment.

   Time frame: 12 weeks

4. Adverse events

   Throughout the entire study all adverse events will be noted. After the final study procedure of the last patient, all adverse events 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 IBS-like symptoms

   Development of post-treatment irritable bowel syndrome like symptoms associated with bezlotoxumab treatment or FMT treatment

   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

   As assessed by PCR

   Time frame: 3 and 12 weeks

9. Fecal microbiota (16S) alfa- and beta-diversity

   As assessed by 16S rRNA amplicon sequencing

   Time frame: Pre-treatment and 3 and 12 weeks

10. Cost-effectiveness

    Costs per cured patient (global and sustained cure) and costs per QALY gained, using the EQ-5D-5L health questionaire that assesses five domains by 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. Patient wellbeing

   As assessed by questionnaire, that includes: 1. self rated health - 5 point scale, higher is worse outcome 2. happiness - 7 points scale, higher is worse outcome 3. optimism - 6 items 4. patient health questionnaire PHQ-9 - 9 items with 4 point scale, higher is worse outcome 5. hospital anxiety and depression scale HADS - 14 items

   Time frame: Pre-treatment and 12 weeks

2. Rate of patients with improved defecation pattern

   As assessed by personal diary

   Time frame: 12 weeks

Individual participant data

Plan to share: No