Less May be More: Loop Ileostomy With Colonic Lavage for Fulminant Clostridium Difficile Colitis A Prospective National Multi-Center Cohort Study

PROTOCOL

1. Study purpose and rationale

i. Specific Aim and Hypothesis: The objective of this study is to determine if loop ileostomy and colonic irrigation reduces 30 day all-cause mortality compared to the current standard of care for fulminant Clostridium difficile colitis (FCDC), total abdominal colectomy with end ileostomy. We hypothesize that loop ileostomy and colonic irrigation (ileostomy) will significantly reduce 30 day all-cause mortality compared to total abdominal colectomy with end ileostomy (TAC). Furthermore, we hypothesize that this intervention will reduce 30-day morbidity, 90 day all-cause mortality and improve gastrointestinal restoration rates compared to TAC.

ii. Significance: With the emergence of a hypervirulent toxin-producing NAP1/027 strain of C. difficile in 2003, C.difficile colitis has become an increasingly common problem (1). Up to 10% of patients with C.difficile infection progress to FCDC with a mortality of 36-80% (1-3). The standard of care for FCDC is a timely TAC; however despite this intervention mortality rates remain high (38-55%) (2,3). The standard of care for FCDC is a TAC. This includes end ileostomy, which becomes permanent in over 65% of patients as reversal necessitates an extensive operation (5). Neal et al. proposed a new surgical approach for FCDC which includes creation of a loop ileostomy, intraoperative colonic lavage with warmed polyethylene glycol via the ileostomy and postoperative antegrade instillation of vancomycin flushes into the diseased colon via the ileostomy. In a single-institution series, this alternative approach for 42 patients was compared to 42 historical controls that underwent TAC (4). While demographics and severity of illness in the control and intervention groups were comparable, the 30 day mortality was significantly decreased in ileostomy compared to TAC groups (19% vs. 50%). To date, this is the only report of this new alternative procedure for FCDC. Neal et al.'s work is a single center, single surgeon series of loop ileostomy cases compared to a historical series of patients treated with TAC. To further investigate their promising results and innovative treatment, we propose a multi-center national (Canadian) prospective cohort study for the evaluation of this intervention compared to controls. 2. Description of study population

i. Basic study design: This is a national, multi-center prospective cohort study to evaluate loop ileostomy and colonic lavage to the standard of care, total abdominal colectomy with end ileostomy. This study will consist of a prospective registry (from 2014 to 2017) with 2 prospective arms: the loop ileostomy group and the control (TAC) group. In addition, we will concurrently perform a retrospective chart review at all participating sites from (from 2010 to 2014) to serve as a third group of historical controls.