Clinical Trial Details
— Status: Terminated
Administrative data
| NCT number |
NCT03756454 |
| Other study ID # |
2018H0348 |
| Secondary ID |
|
| Status |
Terminated |
| Phase |
Phase 4
|
| First received |
|
| Last updated |
|
| Start date |
August 19, 2019 |
| Est. completion date |
May 23, 2022 |
Study information
| Verified date |
May 2023 |
| Source |
Ohio State University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
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.
Description:
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.
