Comparing the Effectiveness of IV Bezlotoxumab Versus Placebo in Decreasing Morbidity and Mortality in Patients With Fulminant C. Diff Requiring Surgery.

NCT03756454 | Terminated Phase 4 FDA Drug

• 1 other identifier: 2018H0348
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Clostridia Difficile Colitis; Clostridium; Sepsis

Outcome Measures

Primary Outcomes (1)

• Mortality

  Monitor for 30-day mortality

  30-days

Secondary Outcomes (4)

• Heart Failure

  30-days

• Respiratory Failure

  30-days

• Renal Failure

  30-days

• Hepatic Failure

  30-days

Study Arms (2)

Bezlotoxumab

EXPERIMENTAL

Patients receiving Bezlotoxumab post-operatively.

Biological: Bezlotoxumab

Normal Saline

PLACEBO COMPARATOR

Patients receiving normal saline as a placebo post-operatively.

Other: Normal Saline

Interventions

Bezlotoxumab BIOLOGICAL

Patients receiving Bezlotoxumab post-operatively.

Bezlotoxumab

Normal Saline OTHER

Placebo

Normal Saline

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Michael E Villarreal, MD: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

The Ohio State University

Columbus, Ohio, 43210, United States

Location

MeSH Terms

Conditions

Enterocolitis, Pseudomembranous; Sepsis

Interventions

bezlotoxumab; Saline Solution

Condition Hierarchy (Ancestors)

Clostridium Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Enterocolitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: 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 in 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical Instructor House Staff - General Surgery

Model Details: 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.

Study Record Dates

• First Submitted: November 26, 2018
• First Posted: November 28, 2018
• Study Start: August 19, 2019
• Primary Completion: May 23, 2022
• Study Completion: May 23, 2022
• Last Updated: May 12, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)