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Safety and Efficacy of Fidaxomicin Versus Placebo for Prophylaxis Against Clostridium Difficile-Associated Diarrhea in Adults Undergoing Hematopoietic Stem Cell Transplantation (MK-5119-001) (DEFLECT-1)

Primary Purpose

Clostridium Difficile-Associated Diarrhea (CDAD)

Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
fidaxomicin
Placebo
Sponsored by
Optimer Pharmaceuticals LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Clostridium Difficile-Associated Diarrhea (CDAD) focused on measuring Clostridium difficile, Clostridium difficile-Associated Diarrhea, Prophylaxis, Hematopoietic Stem Cell Transplantation

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Male or female 18 years of age or older.
  • Females of childbearing potential must be using an adequate and reliable method of contraception (e.g., abstinence, barrier with additional spermicide foam or jelly, intrauterine device, hormonal contraception). Males and females must agree to avoid conception during treatment and for four weeks following the end of study treatment.
  • Is undergoing HSCT with planned Fluoroquinolone prophylaxis.
  • Informed consent is provided.

Exclusion Criteria:

  • Ongoing active CDAD infection (as evidenced by clinical signs of diarrhea along with the presence of either toxin A and/or B [or their respective genes, tcdA and/or tcdB] of C. difficile in the stool) or current treatment for CDAD.
  • Undergoing cord blood transplants.
  • Has fulminant colitis, toxic megacolon, or ileus.
  • A history of inflammatory bowel disease (ulcerative colitis or Crohn's disease).
  • Women who are pregnant or are actively breast feeding (all women of childbearing potential must have a negative pregnancy test result prior to dosing study drug).
  • Use of any drugs potentially useful in the treatment of CDAD (e.g. oral Vancomycin, Metronidazole, oral Bacitracin, Fusidic Acid, Rifaximin, and Nitazoxanide).
  • Any other condition that, in the opinion of the investigator, would jeopardize the safety or rights of the participant in the study, would make it unlikely for the participant to complete the study, or would confound the results of the study.
  • Participation in other clinical research studies utilizing an investigational agent within one month prior to screening and during the study treatment period.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Active Comparator

    Placebo Comparator

    Arm Label

    Fidaxomicin

    Placebo

    Arm Description

    200 mg Fidaxomicin tablet once daily for no longer than 40 days

    Placebo tablet once daily for no longer than 40 days

    Outcomes

    Primary Outcome Measures

    Percentage of Participants With Occurrence of CDAD From Start of Study Treatment up to 30 Days Post-treatment Follow-up.
    CDAD is defined as follows: Diarrhea: (change in bowel habits with >3 unformed bowel movements in a 24 hour period) and the presence of either toxin A and/or B (or their respective genes, tcdA and/or tcdB) of C. difficile in the stool determined by C. difficile toxin assay. Wald 95% Confidence Intervals (CI) are presented.

    Secondary Outcome Measures

    Percentage of Participants With Occurrence of CDAD From Start of Study Treatment up to 60 Days Post-treatment.
    CDAD is defined as follows: Diarrhea: (change in bowel habits with >3 unformed bowel movements in a 24 hour period) and the presence of either toxin A and/or B (or their respective genes, tcdA and/or tcdB) of C. difficile in the stool determined by C. difficile toxin assay. Wald 95% Confidence Intervals (CI) are presented.
    Percentage of Participants With Occurrence of CDAD From Start of Study Treatment up to Day 70 of Study.
    CDAD is defined as follows: Diarrhea: (change in bowel habits with >3 unformed bowel movements in a 24 hour period) and the presence of either toxin A and/or B (or their respective genes, tcdA and/or tcdB) of C. difficile in the stool determined by C. difficile toxin assay. Wald 95% Confidence Intervals (CI) are presented.

    Full Information

    First Posted
    September 19, 2012
    Last Updated
    August 16, 2018
    Sponsor
    Optimer Pharmaceuticals LLC
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    1. Study Identification

    Unique Protocol Identification Number
    NCT01691248
    Brief Title
    Safety and Efficacy of Fidaxomicin Versus Placebo for Prophylaxis Against Clostridium Difficile-Associated Diarrhea in Adults Undergoing Hematopoietic Stem Cell Transplantation (MK-5119-001)
    Acronym
    DEFLECT-1
    Official Title
    DEFLECT-1: A Phase 3b Multi-Center, Double-Blind, Randomized, Placebo Controlled Study to Demonstrate the Safety and Efficacy of Fidaxomicin for Prophylaxis Against Clostridium Difficile-Associated Diarrhea in Adults Undergoing Hematopoietic Stem Cell Transplantation
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    August 2018
    Overall Recruitment Status
    Completed
    Study Start Date
    October 10, 2012 (Actual)
    Primary Completion Date
    March 18, 2015 (Actual)
    Study Completion Date
    April 16, 2015 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Optimer Pharmaceuticals LLC

    4. Oversight

    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    The objective of this study is to demonstrate the efficacy and safety of Fidaxomicin versus placebo for prophylaxis against Clostridium difficile-Associated Diarrhea (CDAD) in adult participants undergoing hematopoietic stem cell transplantation (HSCT). The primary hypothesis is that Fidaxomicin is superior to placebo in preventing CDAD in participants undergoing HSCT.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Clostridium Difficile-Associated Diarrhea (CDAD)
    Keywords
    Clostridium difficile, Clostridium difficile-Associated Diarrhea, Prophylaxis, Hematopoietic Stem Cell Transplantation

    7. Study Design

    Primary Purpose
    Prevention
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantInvestigator
    Allocation
    Randomized
    Enrollment
    611 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Fidaxomicin
    Arm Type
    Active Comparator
    Arm Description
    200 mg Fidaxomicin tablet once daily for no longer than 40 days
    Arm Title
    Placebo
    Arm Type
    Placebo Comparator
    Arm Description
    Placebo tablet once daily for no longer than 40 days
    Intervention Type
    Drug
    Intervention Name(s)
    fidaxomicin
    Other Intervention Name(s)
    DIFICID, DIFICLIR, OPT-80, PAR-101
    Intervention Description
    Fidaxomicin 200 mg tablet once daily from the start (+/- 2 days) of condition (prior to transplantation) or at the time of Fluoroquinolone initiation. Study drug treatment will continue until 7 days after either neutrophil engraftment or the completion of any Fluoroquinolone antibiotic regimen (whichever occurs later). Study drug treatment will stop at onset of CDAD or no longer than 40 days of duration, even if other antibiotics are still administered or neutrophil engraftment extends beyond 40 days.
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo
    Intervention Description
    Placebo tablet once daily from the start (+/- 2 days) of condition (prior to transplantation) or at the time of Fluoroquinolone initiation. Treatment will continue until 7 days after either neutrophil engraftment or the completion of any Fluoroquinolone antibiotic regimen (whichever occurs later). Treatment will stop at onset of CDAD or no longer than 40 days of duration, even if other antibiotics are still administered or neutrophil engraftment extends beyond 40 days.
    Primary Outcome Measure Information:
    Title
    Percentage of Participants With Occurrence of CDAD From Start of Study Treatment up to 30 Days Post-treatment Follow-up.
    Description
    CDAD is defined as follows: Diarrhea: (change in bowel habits with >3 unformed bowel movements in a 24 hour period) and the presence of either toxin A and/or B (or their respective genes, tcdA and/or tcdB) of C. difficile in the stool determined by C. difficile toxin assay. Wald 95% Confidence Intervals (CI) are presented.
    Time Frame
    Up to 30 days post-treatment
    Secondary Outcome Measure Information:
    Title
    Percentage of Participants With Occurrence of CDAD From Start of Study Treatment up to 60 Days Post-treatment.
    Description
    CDAD is defined as follows: Diarrhea: (change in bowel habits with >3 unformed bowel movements in a 24 hour period) and the presence of either toxin A and/or B (or their respective genes, tcdA and/or tcdB) of C. difficile in the stool determined by C. difficile toxin assay. Wald 95% Confidence Intervals (CI) are presented.
    Time Frame
    Up to 60 days post-treatment
    Title
    Percentage of Participants With Occurrence of CDAD From Start of Study Treatment up to Day 70 of Study.
    Description
    CDAD is defined as follows: Diarrhea: (change in bowel habits with >3 unformed bowel movements in a 24 hour period) and the presence of either toxin A and/or B (or their respective genes, tcdA and/or tcdB) of C. difficile in the stool determined by C. difficile toxin assay. Wald 95% Confidence Intervals (CI) are presented.
    Time Frame
    Up to Day 70 of study

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Male or female 18 years of age or older. Females of childbearing potential must be using an adequate and reliable method of contraception (e.g., abstinence, barrier with additional spermicide foam or jelly, intrauterine device, hormonal contraception). Males and females must agree to avoid conception during treatment and for four weeks following the end of study treatment. Is undergoing HSCT with planned Fluoroquinolone prophylaxis. Informed consent is provided. Exclusion Criteria: Ongoing active CDAD infection (as evidenced by clinical signs of diarrhea along with the presence of either toxin A and/or B [or their respective genes, tcdA and/or tcdB] of C. difficile in the stool) or current treatment for CDAD. Undergoing cord blood transplants. Has fulminant colitis, toxic megacolon, or ileus. A history of inflammatory bowel disease (ulcerative colitis or Crohn's disease). Women who are pregnant or are actively breast feeding (all women of childbearing potential must have a negative pregnancy test result prior to dosing study drug). Use of any drugs potentially useful in the treatment of CDAD (e.g. oral Vancomycin, Metronidazole, oral Bacitracin, Fusidic Acid, Rifaximin, and Nitazoxanide). Any other condition that, in the opinion of the investigator, would jeopardize the safety or rights of the participant in the study, would make it unlikely for the participant to complete the study, or would confound the results of the study. Participation in other clinical research studies utilizing an investigational agent within one month prior to screening and during the study treatment period.
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Medical Director
    Organizational Affiliation
    Merck Sharp & Dohme LLC
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing Plan Description
    https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
    IPD Sharing URL
    http://engagezone.msd.com/ds_documentation.php
    Citations:
    PubMed Identifier
    29893798
    Citation
    Mullane KM, Winston DJ, Nooka A, Morris MI, Stiff P, Dugan MJ, Holland H, Gregg K, Adachi JA, Pergam SA, Alexander BD, Dubberke ER, Broyde N, Gorbach SL, Sears PS. A Randomized, Placebo-controlled Trial of Fidaxomicin for Prophylaxis of Clostridium difficile-associated Diarrhea in Adults Undergoing Hematopoietic Stem Cell Transplantation. Clin Infect Dis. 2019 Jan 7;68(2):196-203. doi: 10.1093/cid/ciy484. Erratum In: Clin Infect Dis. 2019 Mar 19;68(7):1254.
    Results Reference
    derived

    Learn more about this trial

    Safety and Efficacy of Fidaxomicin Versus Placebo for Prophylaxis Against Clostridium Difficile-Associated Diarrhea in Adults Undergoing Hematopoietic Stem Cell Transplantation (MK-5119-001)

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