Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03756454
Recruitment Status : Recruiting
First Posted : November 28, 2018
Last Update Posted : August 28, 2019
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Michael E Villarreal, MD, Ohio State University

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.

Condition or disease Intervention/treatment Phase
Clostridia Difficile Colitis Clostridium; Sepsis Biological: Bezlotoxumab Other: Normal Saline Phase 4

Detailed 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.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: 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.
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description: 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.
Primary Purpose: Treatment
Official Title: A Prospective, Double-blind, Randomized, and Controlled Clinical Trial to Compare the Effectiveness of Intravenous Bezlotoxumab (10 mg/kg) Versus Placebo in Decreasing Morbidity and Mortality in Patients With Fulminant Clostridioides Difficile Requiring Surgical Intervention.
Actual Study Start Date : August 19, 2019
Estimated Primary Completion Date : July 2021
Estimated Study Completion Date : July 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Bezlotoxumab
Patients receiving Bezlotoxumab post-operatively.
Biological: Bezlotoxumab
Patients receiving Bezlotoxumab post-operatively.

Placebo Comparator: Normal Saline
Patients receiving normal saline as a placebo post-operatively.
Other: Normal Saline
Placebo




Primary Outcome Measures :
  1. Mortality [ Time Frame: 30-days ]
    Monitor for 30-day mortality


Secondary Outcome Measures :
  1. Heart Failure [ Time Frame: 30-days ]
    Monitor for development of heart failure

  2. Respiratory Failure [ Time Frame: 30-days ]
    Monitor for development of respiratory failure

  3. Renal Failure [ Time Frame: 30-days ]
    Monitor for development of renal failure

  4. Hepatic Failure [ Time Frame: 30-days ]
    Monitor for development of hepatic failure



Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03756454


Contacts
Layout table for location contacts
Contact: Michael E Villarreal, MD 2108602809 michael.villarreal@osumc.edu

Locations
Layout table for location information
United States, Ohio
The Ohio State University Recruiting
Columbus, Ohio, United States, 43210
Contact: Michael E Villarreal, MD    614-293-8000    michael.villarreal@osumc.edu   
Sponsors and Collaborators
Michael E Villarreal, MD
Merck Sharp & Dohme Corp.

Layout table for additonal information
Responsible Party: Michael E Villarreal, MD, Clinical Instructor House Staff - General Surgery, Ohio State University
ClinicalTrials.gov Identifier: NCT03756454     History of Changes
Other Study ID Numbers: 2018H0348
First Posted: November 28, 2018    Key Record Dates
Last Update Posted: August 28, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Additional relevant MeSH terms:
Layout table for MeSH terms
Colitis
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Colonic Diseases
Intestinal Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs