Comparing the Effectiveness of IV Bezlotoxumab Versus Placebo in Decreasing Morbidity and Mortality in Patients With Fulminant C. Diff Requiring Surgery.
Comparing the Effectiveness of IV Bezlotoxumab Versus Placebo in Decreasing Morbidity and Mortality in Patients With Fulminant C. Diff Requiring Surgery.
A new medication, Bezlotoxumab, has been approved for treatment of recurrent Clostridium
 difficile diarrhea by the U.S. Food and Drug Administration. The way this new medication
 works, is by binding the toxin produced by C. difficile bacteria and preventing damage to the
 large bowel. The toxin, and not the bacteria, is responsible for the damage, resulting in the
 clinical symptoms seen in patients. Sometimes, the infection can make a patient severely ill
 with organ failure and death. If severe enough, the infection requires surgery to remove the
 large bowel and allow the patient a better chance at recovery. Even with surgery and removal
 of the bowel, patients can continue to be severely ill and have a very high rate of
 mortality. The toxin that injures the large bowel has been shown to obtain access to systemic
 circulation because of the injury to the bowel. At this time, the investigators continue
 antibiotics and supportive care to help patients recover post-operatively, as the
 investigators do not have other interventions in this critical population. Bezlotoxumab is
 known to bind this toxin and stop it from causing further injury in the bowel; it has the
 potential to bind the systemic toxin to prevent further damage throughout the body. This
 study is proposing that this new medication, Bezlotoxumab, can be added to the current
 standard of care for severe infection that requires surgery, and result in a decrease of the
 complications associated with this disease process. In this study, some patients will receive
 the medication after surgery; others will receive extra fluid. The investigators will not
 know who received which in order to decrease any bias in the results. All participants will
 receive similar post-operative care and be monitored closely. When enough patients are
 enrolled in the study, the results will be evaluated.
Study Design This will be an interventional prospective, randomized, double-blinded
 controlled trial performed at a single center. Prospective data will be collected of all
 consenting patients with a diagnosis of either initial or recurrent fulminant C. difficile
 colitis requiring surgical intervention. The data to be collected includes standard-of-care
 blood draws; no extra lab draws are planned for this trial. In the event labs are not drawn,
 the investigators will plan to obtain serum creatinine, total bilirubin, and platelet counts
 to continue SOFA score evaluations while the patient is in the surgical ICU. Consent will be
 obtained either from the patient or their legally authorized representative. Inclusion
 criteria will be all patients over the age of eighteen with diagnosed fulminant C. difficile
 colitis requiring surgical colectomy with end ileostomy. Surgical intervention will be
 determined by the operating surgeon at the time of initial consult assessment and during the
 follow-up assessments while the patient is hospitalized. Patients may be excluded on the
 account they are pregnant, prisoners/ incarcerated, have a history of congestive heart
 failure, or have received IVIG within 30 days of randomization to exclusion criteria.

 Randomization will be performed per best common practice guidelines with a computer-generated
 randomization process and hospital investigational pharmacy blinding processes into both a
 therapeutic arm (Bezlotoxumab) and a placebo (normal saline) arm of the study. All current
 standards of care will continue to be administered in these patients, regardless of their
 respective study arm. To control for the antibiotics administered, the patients will need to
 be stratified according to the standard-of-care antibiotics and balanced in regards to this
 variable. Current standard of care therapy at our institution for fulminant C. difficile
 colitis includes Vancomycin (both oral and rectal, if needed) and intravenous Metronidazole.
 Fulminant C. difficile colitis is defined, per our guidelines, as proven infection with
 hypotension/ shock, ileus, or megacolon.

 Upon conclusion of the surgical intervention, the Anesthesia or nursing team will administer
 the trial medication, Bezlotoxumab, or the placebo, normal saline. Dosing is planned to be
 ten milligrams per kilogram, which is standard dosing for therapeutic Bezlotoxumab approved
 for use by the U.S. Food and Drug Administration. This dose will be administered as a
 one-time single-infusion dose administered over the span of one hour. The placebo
 administration of normal saline will be at the same dosing with a single-infusion over one
 hour. The patient will receive standard of care post-operative management and the information
 obtained from standard-of-care lab draws will be assessed throughout their hospital stay. The
 patient will be seen and evaluated in clinic during the post-operative period at the
 one-month follow-up and either in clinic or via telephone at their three-month and six-month
 follow-up.
Inclusion Criteria:

 -  > 18 years old, diagnosed C diff colitis requiring surgical intervention

 Exclusion Criteria:

 -  CHF previously diagnosed, pregnancy, prisoners/ incarcerated, previous administration
 of IVIG within 30-days of randomization