Clinical trial NCT01670149: Rifaximin for Preventing Relapse of Clostridium Associated Diarrhoea
Official title: A Randomised Placebo Controlled Trial of "Follow on" Rifaximin for the Prevention of Relapse of Clostridium Associated Diarrhoea
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Clostridium Difficile Infection
Keywords: Clostridium difficile
Diarrhoea
Rifaximin
Lead sponsor: University of Nottingham
Sponsor class: OTHER
Collaborators: name: National Institute for Health Research, United Kingdom
First posted: 2012-08-21
Enrollment: 151
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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: 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

Eligibility criteria: Inclusion criteria:

1. Men / Women aged 18 and over (We will also include those adults who lack mental capacity for whom we have a legal representative)
2. Successful treatment of clinically diagnosed CDAD using standard therapy (metronidazole or vancomycin given according to standard local hospital guidelines).

Exclusion criteria:

1. Woman of child bearing potential and not willing to use at least one highly effective contraceptive method throughout the study
2. Male with spouse/partner of child bearing potential and not willing to use condoms
3. Pregnant or breast feeding
4. Unable to swallow tablets
5. Life expectancy of \<4 weeks
6. 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)
7. \>5 days post standard therapy (metronidazole or vancomycin) for clinically diagnosed CDAD
8. Taking ciclosporin

Primary outcomes:
measure: Difference in % relapse between Rifaximin and placebo at 12 weeks
timeFrame: 12 weeks
Secondary outcomes:
measure: Proportion relapsed, re-hospitalisation and bowel symptoms
timeFrame: 12 weeks - 6 months
Other outcomes:
Locations:
city: Nottingham
country: United Kingdom
facility: Nottingham Clinical Trials Unit (NCTU), Queen's Medical Centre
state: Nottinghamshire
Study officials:
affiliation: Nottingham University Hospitals NHS Trust
name: Aida Jawhari, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Major G, Bradshaw L, Boota N, Sprange K, Diggle M, Montgomery A, Jawhari A, Spiller RC; RAPID Collaboration Group. Follow-on RifAximin for the Prevention of recurrence following standard treatment of Infection with Clostridium Difficile (RAPID): a randomised placebo controlled trial. Gut. 2019 Jul;68(7):1224-1231. doi: 10.1136/gutjnl-2018-316794. Epub 2018 Sep 25.
citation: Stevenson EC, Major GA, Spiller RC, Kuehne SA, Minton NP. Coinfection and Emergence of Rifamycin Resistance during a Recurrent Clostridium difficile Infection. J Clin Microbiol. 2016 Nov;54(11):2689-2694. doi: 10.1128/JCM.01025-16. Epub 2016 Aug 24.