Optimal Surgical Treatment Of Fulminant Clostridium Difficile Colitis

This study has been terminated.
(Numer of eligible patients markedly decreased since the initiation of the study.)
Sponsor:
Information provided by (Responsible Party):
Marc A. de Moya, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT01441271
First received: September 17, 2011
Last updated: May 19, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention
Clostridium Difficile Colitis
Procedure: Ileal diversion and lavage
Procedure: total abdominal colectomy

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Diverting Loop Ileostomy and Colonic Lavage: An Alternative To Total Abdominal Colectomy For The Treatment Of Fulminant Clostridium Difficile Colitis. A Randomized Controlled Trial.

Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • Mortality [ Designated as safety issue: No ]
    Both groups will be compared using mortality as the primary outcome.


Secondary Outcome Measures:
  • ICU Length of Stay (LOS [ Designated as safety issue: No ]
    Length of stay in ICU (days)

  • Hospital LOS [ Designated as safety issue: No ]
    Length of stay in hospital (days)

  • ventilation days [ Designated as safety issue: No ]
    Days that patient is being mechanically ventilated.

  • morbidity [ Designated as safety issue: No ]
    Morbidity measured as: DVT/PE rate, surgical site infection, urinary tract infection, pneumonia, inadvertent enterotomy, re-operation related to ileostomy, and 'ileostomy tube' migration.


Enrollment: 1
Study Start Date: September 2012
Study Completion Date: September 2013
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01441271

Locations
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
Massachusetts General Hospital
Investigators
Principal Investigator: Marc de Moya, MD Massachusetts General Hospital
  More Information

No publications provided

Responsible Party: Marc A. de Moya, Assistant Professor of Surgery, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT01441271     History of Changes
Other Study ID Numbers: 2012-P-000138/1; MGH
Study First Received: September 17, 2011
Last Updated: May 19, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Colitis
Colonic Diseases
Digestive System Diseases
Gastroenteritis
Gastrointestinal Diseases
Intestinal Diseases

ClinicalTrials.gov processed this record on October 20, 2014