Use Of Oral Fidaxomicin Vs. Oral Vancomycin For Clostridium Difficile Infection In Patients With Spinal Cord Injury

Role of Fidaxomicin in a Patient Population With Problematic Clostridium Difficile Infection

The primary purpose of this study is to compare the clinical outcomes of cure and recurrence of Clostridium difficile infection in spinal cord injured patients who are treated with oral Fidaxomicin vs. oral Vancomycin. The secondary aim of this study is to compare the overall costs of treatment of Clostridium difficile infection in the two study groups.

Study Overview

• Status: Terminated
• Conditions: Spinal Cord Injury; Clostridium Difficile
• Intervention / Treatment: Drug: Fidaxomicin 200 mg; Drug: Placebo; Drug: Vancomycin

Detailed Description

In recent clinical trials, comparing oral Vancomycin versus oral Fidaxomicin to treat Clostridium difficile, oral Fidaxomicin was shown to be the same in effectiveness as oral Vancomycin, but showed a decrease in recurrence of Clostridium difficile by ten percentage points. Based on experience with patients in our 40-bed spinal cord injury unit at the Michael E. DeBakey VA Medical Center (MEDVAMC), Clostridium difficile infection is more problematic in patients with spinal cord injury than in the general hospitalized patient population. Compared to the general population of hospitalized patients, patients with spinal cord injury are more likely to have: (1) a higher transmission of Clostridium difficile from one patient to another often via the health care worker due to their having a neurogenic bowel (2) a longer and more complicated course of Clostridium difficile infection-associated diarrhea since neurogenic bladder may delay excretion of toxins and predispose to bowel accidents; and (3) a higher overall cost of treatment in terms of extended hospitalization (most patients with spinal cord injury who suffer from Clostridium difficile infection do not get discharged from the hospital until the symptoms of course of Clostridium difficile infection are resolved. Fidaxomicin is the first in a new class of narrow spectrum macrocyclic antibiotic drugs. It is a non-systemic, meaning it is minimally absorbed into the bloodstream, and it is bactericidal, meaning it attacks and kills the bacteria it comes in contact with. It has demonstrated selective eradication of pathogenic Clostridium difficile with minimal disruption to the numerous species of bacteria that make up the normal, healthy intestinal flora. The maintenance of normal physiological conditions in the colon can reduce the probability of recurrence of a Clostridium difficile infection. Since clearance of Clostridium difficile infections is problematic in the spinal cord injured patients, this antimicrobial agent may show a trend for clinical superiority and a reduction in recurrence of infection within the spinal cord injury population resulting in a shorter hospital stays and reduced costs.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Michael E. DeBakey VA Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Ability of subject to provide an informed consent
• Legally Authorized Representative-Adult must provide consent in case the subject is unable to consent
• Diagnosis of Clostridium difficile disease based on clinical manifestations (change in bowel habits, at least 2 more unformed bowel movements as compared to baseline neurogenic bowel function in the same patient in the 24-hour period prior to randomization)
• Lab data (positive polymerase chain reaction test for Clostridium difficile in a stool specimen obtained within 72 hours before randomization)
• Patient has not received antibiotics that are active against Clostridium difficile for any more than 24 hours prior to being screened for this study.

Exclusion Criteria:

• Receipt of agents (oral Vancomycin, oral or IV Metronidazole, oral rifamdin, oral bacitracin, or oral fusidic acid) that are active against Clostridium difficile for longer than 24 hours after randomization
• Life-threatening or fulminant Clostridium difficile infection, presence of toxic megacolon, and history of inflammatory bowel disease (Crohn's disease and ulcerative colitis)
• Allergy to study medications.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fidaxomicin Arm; Oral Fidaxomicin 200 mg every 12 hours (Placebo for 2 doses) for 10 days	Drug: Fidaxomicin 200 mg; Fidaxomicin 200 mg every 12 hours; Other Names: Dificid; Drug: Placebo; 1 dose of placebo every 6 hours x 2 doses; Other Names: Cellulose Capsule
Active Comparator: Vancomycin Arm; Oral Vancomycin 125 mg every 6 hours for 10 days	Drug: Vancomycin; Vancomycin 125 mg every 6 hours; Other Names: Vancocin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cure of Clostridium Difficile	Decrease in number and frequency of loose stools	10 Days

Secondary Outcome Measures

Outcome Measure	Time Frame
Cost Benefit Analysis	Hospitalization cost 6 months before and 6 months after treatment

Collaborators and Investigators

• Sponsor: Baylor College of Medicine
• Collaborators: Cubist Pharmaceuticals LLC
• Investigators: Principal Investigator: Rabih O Darouiche, MD, Michael E. DeBakey VA Medical Center

Study record dates

Study Major Dates

• Study Start: February 1, 2014
• Primary Completion (Actual): October 1, 2016
• Study Completion (Actual): October 1, 2016

Study Registration Dates

• First Submitted: January 30, 2015
• First Submitted That Met QC Criteria: January 30, 2015
• First Posted (Estimate): February 4, 2015

Study Record Updates

• Last Update Posted (Estimate): October 13, 2016
• Last Update Submitted That Met QC Criteria: October 12, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Infections; Wounds and Injuries; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Trauma, Nervous System; Spinal Cord Diseases; Spinal Cord Injuries; Clostridium Infections; Anti-Infective Agents; Anti-Bacterial Agents; Vancomycin; Fidaxomicin
• Other Study ID Numbers: IIS-000116; H-32358 (Other Identifier: Baylor College of Medicine)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Enrollment to low for statistical analysis.