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Optimal Treatment for Recurrent Clostridium Difficile (OpTION)

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ClinicalTrials.gov Identifier: NCT02667418
Recruitment Status : Recruiting
First Posted : January 28, 2016
Last Update Posted : January 4, 2019
Sponsor:
Information provided by (Responsible Party):
VA Office of Research and Development

Brief Summary:
The purpose of this study is to determine whether fidaxomicin and vancomycin followed by taper and pulse vancomycin treatment are superior to standard vancomycin treatment for the treatment of recurrent Clostridium difficile infection.

Condition or disease Intervention/treatment Phase
Clostridium Difficile Fidaxomicin Vancomycin Drug: Fidaxomicin Drug: Vancomycin with Taper/Pulse Drug: Vancomycin Phase 4

Detailed Description:

Clostridium difficile is the most common cause of healthcare-associated infectious diarrhea among adults in industrialized countries. In addition to diarrhea, C. difficile infection (CDI) may also result in serious complications such as shock, toxic megacolon, colectomy, and death. The Centers for Disease Control and Prevention (CDC) has estimated C. difficile results in 250,000 hospital infections, 14,000 deaths, and $1 billion in excess costs annually. Recurrent CDI is the most challenging clinical dilemma facing clinicians who treat this disease. An estimated 30% of patients who respond to initial treatment with either vancomycin or metronidazole develop recurrent CDI, usually within 1-4 weeks of completing treatment.

The primary objective of this study is to determine whether 1) standard fidaxomicin treatment and 2) standard vancomycin treatment followed by taper and pulse vancomycin treatment are superior to standard vancomycin treatment alone for sustained clinical response at day 59 for all treatments, for participants with either their first or second recurrence of CDI. Veterans presenting with a first or second CDI recurrence will be screened, consented and randomly assigned in a double-blind manner to one of three treatment groups: 1) a 10 day course of oral vancomycin (VAN-TX), 2) a 10 day course of fidaxomicin (FID-TX) or 3) a 31 day course of vancomycin which includes a taper and pulse following daily treatment (VAN-TP/P). Symptom resolution is defined as an improvement or resolution of diarrhea (<3 unformed bowel movements over 24 hours) for 48 consecutive hours compared to the participant's baseline. Recurrence is defined as having diarrhea (>3 loose or semi-formed stools over 24 hours for 48 consecutive hours). A sample size of 546 randomized study participants is required to obtain at least 81% power to detect a 16% absolute difference (expected proportion of 31% in the VAN-TX group) in sustained clinical response (D- COM) proportion 1) between the FID-TX group and the VAN-TX group and 2) between the VAN-TP/P group and VAN-TX group at the 0.05 significance level. It was observed throughout the pilot phase that the original goal of 7 participants per site per year is overestimated. We expect sites will recruit at a more realistic rate of 6 participants (on average) per site per year for sites that will primarily recruit from the main hospital and nearby CBOCS, and 9 participants (on average) per site per year for sites that could partner with independent VAMCs (Independent VAMCs LSI Application will be reviewed and approved by Central IRB) that are close in distance to allow a shared site coordinator (WOC appointed) at an increased funding level. Some sites may recruit more to reach the overall goal. Given revised anticipated recruitment rate and in consideration of sites' variability on start-up dates, different level of recruitment across sites, and logistics on replacement of underperformed sites with backup sites, the study is expected to complete enrollment of 546 participants within 6 years with 90 days of follow-up. This includes 2 years of pilot phase plus transitioning period from pilot phase to full study, and 4 years of full study. There were 6 sites in the pilot phase and will have 24 sites in full phase (including 5 pilot sites and 19 additional sites). This assumes that 30% of Veterans with CDI have a recurrence and 20% of them will enroll in the study.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 546 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: CSP #596 - Optimal Treatment for Recurrent Clostridium Difficile Infection
Actual Study Start Date : December 21, 2015
Estimated Primary Completion Date : May 31, 2022
Estimated Study Completion Date : May 31, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Fidaxomicin
Standard 10-day fidaxomicin treatment for Clostridium difficile
Drug: Fidaxomicin
200 mg PO twice daily for 10 days

Vancomycin T/P
Standard 10-day vancomycin treatment followed by taper and pulse vancomycin treatment for Clostridium difficile
Drug: Vancomycin with Taper/Pulse
125 mg PO four times daily for 10 days, followed by 125 mg once daily x 7 days, then once every other day x 7 days, then once every 3rd day x 7 days

Vancomycin
Standard 10-day vancomycin treatment for Clostridium difficile
Drug: Vancomycin
125 mg PO for times daily for 10 days




Primary Outcome Measures :
  1. Determine symptom resolution during treatment without any of the following: diarrhea recurrence; other non-fatal clinical events including severe abdominal pain, toxic megacolon, and colectomy; and death. [ Time Frame: Day 59 for all treatment regimens. ]

    The Primary outcome will be sustained clinical response as measured at study day 59 for all treatment regimens. Sustained clinical response is a composite outcome that includes symptom resolution during treatment without any of the following (as assessed on day 59):

    1. Diarrhea recurrence
    2. Other non-fatal clinical events including severe abdominal pain, toxic megacolon (where diarrhea ceases but is not a beneficial outcome), and colectomy
    3. Death


Secondary Outcome Measures :
  1. CDI Composite outcome measure [ Time Frame: Day 59 for all treatment regimens. ]
    CDI Composite Outcome Measure (CDI-COM) is sustained clinical response without recurrent CDI (defined as diarrhea plus confirmation of toxigenic C. difficile or its toxins in stool) as measured at study day 59 for all three treatment regimens. Sustained response will be defined using the same composite endpoint criteria as were used in the D-COM outcome but without recurrent CDI on or before day 59.



Information from the National Library of Medicine

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

Inclusion Criteria:

  • Informed consent obtained and signed
  • Age > 18
  • If female, participant must not be pregnant or nursing

    • Negative pregnancy test required for females <61 years of age or without prior hysterectomy
  • Confirmed current diagnosis of CDI, determined by having

    • >3 loose or semi-formed stools for participants over 24 hours AND
    • Positive stool assay for C. difficile
    • EIA positive for toxin A/B; or
    • Cytotoxin assay; or
    • Nucleic Acid Amplification Test (NAAT, PCR or LAMP) based detection of toxigenic C. difficile
  • Current episode represents the first recurrent episode of CDI within 3 months of the primary CDI episode in a patient who has not had CDI in the 3 months prior to the primary episode OR a second recurrent CDI episode occurring within 3 months of the first recurrent episode, as defined above

    • At least one of the previous CDI episodes must have been confirmed by a stool assay for C. difficile

Exclusion Criteria:

  • Inability to provide informed consent
  • Inability to take oral capsules
  • Receipt of >72 hours of antibiotics considered effective in the treatment of CDI, including:

    • metronidazole
    • vancomycin
    • fidaxomicin
    • nitazoxanide
    • rifaximin
  • Prior infusion of bezlotoxumab within the previous 6 months
  • Known presence of fulminant CDI, including hypotension, severe ileus or GI obstruction or incipient toxic megacolon
  • Receipt of more than a single course of oral vancomycin, fidaxomicin, or a vancomycin tapering regimen since the primary episode of CDI as defined above
  • Known allergy to vancomycin or fidaxomicin
  • Acute or chronic diarrhea due to inflammatory bowel disease or other cause (e.g., presence of an ileostomy or colostomy) that would confound evaluation of response to CDI treatment
  • Anticipation of need for long term systemic antibiotic treatment (beyond 7 days)

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): NCT02667418


Contacts
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Contact: Michelle Johnson (708) 202-8387 ext 27001 Michelle.Johnson5@va.gov

  Show 27 Study Locations
Sponsors and Collaborators
VA Office of Research and Development
Investigators
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Study Chair: Stuart B. Johnson, MD BA Edward Hines Jr. VA Hospital, Hines, IL
Study Chair: Dale N Gerding, MD Edward Hines Jr. VA Hospital, Hines, IL

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Responsible Party: VA Office of Research and Development
ClinicalTrials.gov Identifier: NCT02667418     History of Changes
Other Study ID Numbers: 596
#15-03 ( Other Identifier: VA Central IRB )
First Posted: January 28, 2016    Key Record Dates
Last Update Posted: January 4, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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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

Keywords provided by VA Office of Research and Development:
Clostridium
Difficile
Fidaxomicin
Vancomycin
Recurrent
Pulse
Taper

Additional relevant MeSH terms:
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Clostridium Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Vancomycin
Fidaxomicin
Anti-Bacterial Agents
Anti-Infective Agents