Rifaximin for Preventing Relapse of Clostridium Associated Diarrhoea

Study Overview
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Brief Summary
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Clostridium difficile associated diarrhoea is an important cause of morbidity in patients treated with antibiotics, especially in hospital. Clinical relapse occurs after up to 30% of initially successful treatments for colitis. Preliminary reports suggest that Rifaximin, a poorly absorbed antibiotic used to treat travellers diarrhoea can prevent relapse. We plan to carry out a randomised placebo controlled trial to test the hypothesis that Rifaximin given in a reducing dose over 4 weeks after successful treatment will reduce the relapse rate.

Detailed Description
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Aims i) To examine efficacy of a follow-on course of Rifaximin given after a successful initial course of standard treatment, in the prevention of relapse in C. difficile associated diarrhoea (CDAD). ii) To examine changes in faecal microbiota in patients given Rifaximin vs. Placebo. Treatment 4 weeks treatment with Rifaximin or Placebo tablets. Tapering dose starting with 2 x 200mg tablets three times a day (total = 1.2g per day) for the 1st 2 weeks, reduced to 1 x 200mg tablet three times a day (total = 0.6g per day) for the 2nd 2 weeks. Primary endpoint: The difference in % relapse between Rifaximin and placebo at 12 weeks

Official Title
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A Randomised Placebo Controlled Trial of Follow on Rifaximin for the Prevention of Relapse of Clostridium Associated Diarrhoea

Conditions
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Clostridium Difficile Infection

Intervention / Treatment
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* Drug: Rifaximin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Men / Women aged 18 and over (We will also include those adults who lack mental capacity for whom we have a legal representative) Successful treatment of clinically diagnosed CDAD using standard therapy (metronidazole or vancomycin given according to standard local hospital guidelines). Exclusion criteria: Woman of child bearing potential and not willing to use at least one highly effective contraceptive method throughout the study Male with spouse/partner of child bearing potential and not willing to use condoms Pregnant or breast feeding Unable to swallow tablets Life expectancy of <4 weeks Hypersensitivity to the active substance, to any rifamycin (e.g. rifampicin or rifabutin) or to any of its excipients (Tablet core: Sodium starch glycolate type A, glycerol distearate, colloidal anhydrous, silica, talc and microcrystalline cellulose. Tablet coating: hypromellose, titanium dioxide (E171), disodium edentate, propylene glycol and red iron oxide E172) >5 days post standard therapy (metronidazole or vancomycin) for clinically diagnosed CDAD Taking ciclosporin

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Identical looking tablet | Drug: Placebo<br>* Tablets<br>|
| Active Comparator: Rifaximin , Xifaxanta™<br>2 weeks of Rifaximin 400mg thrice daily then 2 weeks of Rifaximin 200mg thrice daily Modified Xifaxanta™ (rifaximin film-coated tablet) manufactured by Alfa Wasermann (AW), | Drug: Rifaximin<br>* Tablets<br>* Other names: Xifaxanta™;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in % relapse between Rifaximin and placebo at 12 weeks | The difference in % relapse between Rifaximin and placebo at 12 weeks | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion relapsed, re-hospitalisation and bowel symptoms | Secondary endpoints: Clinical: Proportion with relapse of CDAD within 6 months Proportion re-hospitalised for CDAD within 6 months Length of in-hospital stay following start of treatment Exploratory: Stool frequency and consistency during 12 weeks after start of treatment Microbiological assessments | 12 weeks - 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Clostridium difficile, Diarrhoea, Rifaximin