Optimal Surgical Treatment Of Fulminant Clostridium Difficile Colitis

Diverting Loop Ileostomy and Colonic Lavage: An Alternative To Total Abdominal Colectomy For The Treatment Of Fulminant Clostridium Difficile Colitis. A Randomized Controlled Trial.

The investigators hypothesize that minimally invasive ileal diversion with intraoperative colonic lavage using a high volume polyethylene glycol/electrolyte solution will clear Clostridium difficile infection resulting in eradication of Fulminant C. difficile colitis (FCDC) while preserving the colon. Furthermore, the investigators hypothesize this will reduce morbidity and mortality compared to total abdominal colectomy.

Study Overview

• Status: Terminated
• Conditions: Clostridium Difficile Colitis
• Intervention / Treatment: Procedure: total abdominal colectomy; Procedure: Ileal diversion and lavage

Detailed Description

Clostridium difficile (C. difficile) affects more than 3 million patients per year in the United States, and is increasing in frequency [2-15]. Approximately 8 % of hospitalized patients are infected with C. difficile [12]. Of these patients 3% - 8% will develop the fulminant disease, defined as C. difficile colitis with significant systemic toxic effects and shock, resulting in need for colectomy or death [2].

Fulminant C. difficile colitis (FCDC) is a highly lethal disease with mortality rates ranging between 12% - 80% [2-6,8-15]. A retrospective study in our own institution identified a 35% mortality rate for FCDC [2].

The indications for surgical management of patients with FCDC are not clearly defined, however most advocate surgical intervention in patients with worsening clinical exams, peritonitis, or patients in shock. Total abdominal colectomy (also called subtotal colectomy) with end ileostomy has been advocated as the operation of choice and has been demonstrated to marginally improve survival compared to non-operative management in these critically ill patients. A total abdominal colectomy has many disadvantages. Most important, mortality rates continue to range from 35-80%. Additionally, total abdominal colectomy (subtotal colectomy) can result in significant morbidity, and many survivors will have a permanent ileostomy.

The new treatment option that will be tested in this randomized controlled trial (RCT) may change the standard of care. Based on a small prospective series from Neal and colleagues [1] the investigators propose an alternative surgical approach for the management of FCDC, which may prove a safer and simpler option. Based on the nature of the disease as a bacterial toxin-mediated mucosal inflammatory process with delayed and indirect systemic threats to life, the investigators think that minimally invasive ileal diversion with intraoperative colonic lavage using a high volume polyethylene glycol/electrolyte solution will clear Clostridium difficile infection resulting in eradication of FCDC while preserving the colon.

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Adult patients >18 years of age
2. Able to provide informed consent, or presence of a legally authorized representative able and willing to provide informed consent
3. Candidates for total abdominal colectomy due to severe, complicated FCDC per consulting surgeon and team providing care
4. Subjects must meet criteria for operative management of FCDC (find in detailed protocol)

Exclusion Criteria:

1. Children (<18 years of age)
2. Allergy or hypersensitivity reaction to study medications: Vancomycin, Metronidazole, GoLytely
3. Intra-operative evidence of colonic perforation
4. Intra-operative evidence of colonic necrosis
5. Pregnancy (this will be ruled out by a urine test at the time of indication for surgery)
6. Prisoners

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: total abdominal colectomy; the standard of care for fulminant clostridium difficile colitis is a total abdominal colectomy	Procedure: total abdominal colectomy; The surgical approach of the colon in a total abdominal colectomy involves a midline incision. The complete colon in the abdomen (from ileum to rectum) will be removed and an end ileostomy is performed.; Other Names: subtotal colectomy
Experimental: Ileal diversion and lavage; The tested intervention in this trial will be: intraoperative colonic lavage using a high volume polyethylene glycol/electrolyte solution, that will clear Clostridium difficile infection resulting in eradication of FCDC while preserving the colon.	Procedure: Ileal diversion and lavage; The surgical approach involves an attempted laparoscopic creation of a loop ileostomy after visually assessing the colon to assure viability. If the loop is unable to be safely performed laparoscopically an open loop ileostomy will be performed. Intraoperatively, 8 liters of warmed polyethylene glycol 3350/electrolyte solution [GoLytely®; Braintree Laboratories] will be infused into the colon via the ileostomy and collected via a rectal drainage tube. Post-operatively, the patients will receive antegrade vancomycin flushes [500 mg in 500 ml of Lactated Ringers; q8 hours for duration of 10 days] via a Malecot catheter [24 French] left in the efferent limb of the ileostomy (Figure 1). Additionally patients will be continued on intravenous metronidazole [500mg q8 hours] for 10 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality	Both groups will be compared using mortality as the primary outcome.	28 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ICU Length of Stay (LOS	14 days	during hospitalization
Hospital LOS	1 year	hospitalization
ventilation days	1 year	while in ICU
morbidity	1 year	during hospitalization

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Investigators: Principal Investigator: Marc de Moya, MD, Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start: September 1, 2012
• Primary Completion (Actual): October 1, 2012
• Study Completion (Actual): September 1, 2013

Study Registration Dates

• First Submitted: September 17, 2011
• First Submitted That Met QC Criteria: September 23, 2011
• First Posted (Estimate): September 27, 2011

Study Record Updates

• Last Update Posted (Estimate): May 1, 2015
• Last Update Submitted That Met QC Criteria: April 29, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Infections; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Enterocolitis; Colitis; Clostridium Infections; Enterocolitis, Pseudomembranous
• Other Study ID Numbers: 2012-P-000138/1; MGH

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No