Abstract
INTRODUCTION: Clostridium difficile infections (CDI) are common, costly and potentially life threatening. Most CDI will respond to antibiotic therapy, but 3%-10% of all patients with CDI will progress to a severe, life-threatening course. Complete removal of the large bowel is indicated for severe CDI. However, the 30-day mortality following surgical intervention for severe CDI ranges from 20% to 70%. A less invasive approach using surgical faecal diversion and direct colonic lavage with polyethylene glycol (PEG) and vancomycin has demonstrated a relative mortality reduction of approximately 50%. As an alternative to these operative approaches, we propose to treat patients with bedside intestinal lavage with PEG and vancomycin instillation via nasojejunal tube, in addition to usual antibiotic management. Preliminary data collected by our research group are encouraging. METHODS AND ANALYSIS: We will conduct a 1-year, single-centre, pilot randomised controlled trial to study this new treatment strategy for patients with severe CDI and additional risk factors for fulminant or complicated infection. After informed consent, patients with severe-complicated CDI without immediate indication for surgery will be randomised to either usual antibiotic treatment or usual antibiotic treatment with the addition of 8 L of PEG lavage via nasojejunal tube. This pilot trial will evaluate our eligibility and enrolment rate, protocol compliance and adverse event rates and provide further data to inform a more robust sample size calculation and protocol modifications for a definitive multicentre trial design. Based on historical data, we anticipate enrolling approximately 24 patients during the 1-year pilot study period.As a pilot study, data will be reported in aggregate. Between-group differences will be assessed in a blinded fashion for evidence of harm, and to further refine our sample size calculation. ETHICS AND DISSEMINATION: This study protocol has been reviewed and approved by our local institutional review board. Results of the pilot trial and subsequent main trial will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT02466698; Pre-results.