Optimal Treatment for Recurrent Clostridium Difficile

NCT02667418 | Terminated Phase 4 Results DMC FDA Drug

• 3 other identifiers: 596#15-031613088
• Study Type: interventional
• Target: 308
• Locations: 2 countries
• Sites: 33

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.

Conditions

Difficile; Fidaxomicin; Vancomycin; Clostridium

Keywords

Clostridium; Difficile; Fidaxomicin; Vancomycin; Recurrent; Pulse; Taper

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Sustained Clinical Response as Measured at Study 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

  Day 59 for all treatment regimens.

Secondary Outcomes (14)

• Sustained Diarrhea Composite Outcome (D-COM) at 28 Days Post End of Therapy

  28 Days Post End of Therapy

• Clostridium Difficile Infection Composite Outcome (CDI-COM)

  Day 59 post randomization

• Symptom Resolution

  Day 10 since randomization

• CDI Recurrence

  Day 90 since randomization

• Diarrhea Recurrence

  Day 90 since randomization

Study Arms (3)

Fidaxomicin

OTHER

Standard 10-day fidaxomicin treatment for Clostridium difficile

Drug: Fidaxomicin

Vancomycin T/P

OTHER

Standard 10-day vancomycin treatment followed by taper and pulse vancomycin treatment for Clostridium difficile

Drug: Vancomycin with Taper/Pulse

Vancomycin

OTHER

Standard 10-day vancomycin treatment for Clostridium difficile

Drug: Vancomycin

Interventions

Vancomycin DRUG

125 mg PO for times daily for 10 days

Vancomycin

Fidaxomicin DRUG

200 mg PO twice daily for 10 days

Fidaxomicin

Vancomycin with Taper/Pulse DRUG

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 T/P

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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)
• Patients with an active diagnosis of COVID-19 will be excluded from the study, but patients who have recovered (per current CDC guidance on discontinuation of transmission-based precautions) can be included in the study.

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (33)

Phoenix VA Health Care System, Phoenix, AZ

Phoenix, Arizona, 85012, United States

Location

Southern Arizona VA Health Care System, Tucson, AZ

Tucson, Arizona, 85723-0001, United States

Location

Central Arkansas Veterans Healthcare System, Little Rock, AR

Little Rock, Arkansas, 72205, United States

Location

VA Loma Linda Healthcare System, Loma Linda, CA

Loma Linda, California, 92357, United States

Location

VA Long Beach Healthcare System, Long Beach, CA

Long Beach, California, 90822, United States

Location

VA Palo Alto Health Care System, Palo Alto, CA

Palo Alto, California, 94304-1290, United States

Location

VA Northern California Health Care System, Mather, CA

Sacramento, California, 95655-4200, United States

Location

VA San Diego Healthcare System, San Diego, CA

San Diego, California, 92161, United States

Location

VA Greater Los Angeles Healthcare System, West Los Angeles, CA

West Los Angeles, California, 90073, United States

Location

Rocky Mountain Regional VA Medical Center, Aurora, CO

Aurora, Colorado, 80045-7211, United States

Location

Bay Pines VA Healthcare System, Pay Pines, FL

Bay Pines, Florida, 33744-0000, United States

Location

North Florida/South Georgia Veterans Health System, Gainesville, FL

Gainesville, Florida, 32608-1135, United States

Location

James A. Haley Veterans' Hospital, Tampa, FL

Tampa, Florida, 33612, United States

Location

Atlanta VA Medical and Rehab Center, Decatur, GA

Decatur, Georgia, 30033-4004, United States

Location

Jesse Brown VA Medical Center, Chicago, IL

Chicago, Illinois, 60612, United States

Location

Edward Hines Jr. VA Hospital, Hines, IL

Hines, Illinois, 60141-3030, United States

Location

Edward Hines Jr. VA Hospital, Hines, IL

Hines, Illinois, 60141, United States

Location

Rehabilitation R&D Service, Baltimore, MD

Baltimore, Maryland, 21202, United States

Location

VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA

Boston, Massachusetts, 02130-4817, United States

Location

VA Ann Arbor Healthcare System, Ann Arbor, MI

Ann Arbor, Michigan, 48105, United States

Location

John D. Dingell VA Medical Center, Detroit, MI

Detroit, Michigan, 48201-1916, United States

Location

Asheville VA Medical Center, Asheville, NC

Asheville, North Carolina, 28805-2576, United States

Location

Durham VA Medical Center, Durham, NC

Durham, North Carolina, 27705-3875, United States

Location

Louis Stokes VA Medical Center, Cleveland, OH

Cleveland, Ohio, 44106-1702, United States

Location

Oklahoma City VA Medical Center, Oklahoma City, OK

Oklahoma City, Oklahoma, 73104-5007, United States

Location

VA Portland Health Care System, Portland, OR

Portland, Oregon, 97207-2964, United States

Location

VA North Texas Health Care System Dallas VA Medical Center, Dallas, TX

Dallas, Texas, 75216-7167, United States

Location

Michael E. DeBakey VA Medical Center, Houston, TX

Houston, Texas, 77030, United States

Location

South Texas Health Care System, San Antonio, TX

San Antonio, Texas, 78229, United States

Location

VA Salt Lake City Health Care System, Salt Lake City, UT

Salt Lake City, Utah, 84148, United States

Location

VA Puget Sound Health Care System Seattle Division, Seattle, WA

Seattle, Washington, 98108, United States

Location

Clement J. Zablocki VA Medical Center, Milwaukee, WI

Milwaukee, Wisconsin, 53295-0001, United States

Location

VA Caribbean Healthcare System, San Juan, PR

San Juan, 00921, Puerto Rico

Location

Related Publications (1)

• Johnson S, Gerding DN, Li X, Reda DJ, Donskey CJ, Gupta K, Goetz MB, Climo MW, Gordin FM, Ringer R, Johnson N, Johnson M, Calais LA, Goldberg AM, Ge L, Haegerich T. Defining optimal treatment for recurrent Clostridioides difficile infection (OpTION study): A randomized, double-blind comparison of three antibiotic regimens for patients with a first or second recurrence. Contemp Clin Trials. 2022 May;116:106756. doi: 10.1016/j.cct.2022.106756. Epub 2022 Apr 7.

  PMID: 35398532 BACKGROUND

MeSH Terms

Conditions

Recurrence

Interventions

Fidaxomicin; Vancomycin; Pulse

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Polyketides; Macrocyclic Compounds; Polycyclic Compounds; Glycopeptides; Glycoconjugates; Carbohydrates; Peptides; Amino Acids, Peptides, and Proteins; Hemodynamics; Cardiovascular Physiological Phenomena; Circulatory and Respiratory Physiological Phenomena

Results Point of Contact

• Title: Dr. Stuart Johnson
• Organization: Hines VA

Stuart.Johnson2@va.gov

708--202-8387

Study Officials

• 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

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 25, 2016
• First Posted: January 28, 2016
• Study Start: February 19, 2016
• Primary Completion: August 7, 2024
• Study Completion: August 31, 2024
• Last Updated: December 15, 2025
• Results First Posted: November 12, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (32); PR (1)