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Safety and Efficacy of DAV132 in Patients at High-Risk for Clostridium Difficile Infection (CDI) (SHIELD)

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03710694
Recruitment Status : Completed
First Posted : October 18, 2018
Last Update Posted : August 30, 2019
Sponsor:
Collaborator:
Syneos Health
Information provided by (Responsible Party):
Da Volterra

Tracking Information
First Submitted Date  ICMJE October 9, 2018
First Posted Date  ICMJE October 18, 2018
Last Update Posted Date August 30, 2019
Actual Study Start Date  ICMJE October 31, 2018
Actual Primary Completion Date August 9, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 17, 2018)
Safety endpoint: Proportion of patients having at least one adverse event (AE) related to DAV132 and/or to fluoroquinolones (FQs) and which relationship to product (DAV132 or FQ) is confirmed by the Independent Adjudication Committee (IAC). [ Time Frame: 51 days after randomization ]
The IAC will review AEs according to the IAC charter, including Clostridium difficile infection (CDI) and antibiotic-associated diarrhea (AAD), in a blinded manner across both treatment groups, and confirm whether each AE is related or not to DAV132 and/or to the FQ received by the patient.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 17, 2018)
  • Safety endpoint: Number of AEs and proportion of patients with at least one AE [ Time Frame: 51 days after randomization ]
  • Efficacy/performance endpoint, clinical:Proportion of patients with CDI [ Time Frame: 51 days after randomization ]
  • Efficacy/performance endpoint, clinical: Proportion of patients with AAD [ Time Frame: 51 days after randomization ]
  • Efficacy/performance endpoint, clinical: Plasma levels of FQs [ Time Frame: Day 4 ]
  • Efficacy/performance endpoint, biological: Level of free fecal concentrations of FQs [ Time Frame: Day 1, Day 4, Day 6, 10 days after the end of FQs ]
    Duration of treatment with FQs ranges from 5 to 21 days, at the discretion of the Investigator
  • Efficacy/performance endpoint, biological: Level of α-diversity of the intestinal microbiota [ Time Frame: Day 1, Day 6, 10 days after the end of FQs, and 30 days after the end of FQs ]
    Duration of treatment with FQs ranges from 5 to 21 days, at the discretion of the Investigator
  • Efficacy/performance endpoint, biological: Change from D1 of α-diversity of the intestinal microbiota [ Time Frame: Day 6, 10 days after the end of FQs, and 30 days after the end of FQs ]
    Duration of treatment with FQs ranges from 5 to 21 days, at the discretion of the Investigator
  • Efficacy/performance endpoint, biological: Levels of β-diversity of the intestinal microbiota [ Time Frame: Day 6, 10 days after the end of FQs, and 30 days after the end of FQs ]
    Duration of treatment with FQs ranges from 5 to 21 days, at the discretion of the Investigator
  • Efficacy/performance endpoint, biological: Proportion of patients with resistant bacteria and/or yeasts in feces [ Time Frame: Baseline and up to 10 days after the end of FQs ]
    Duration of treatment with FQs ranges from 5 to 21 days, at the discretion of the Investigator
  • Efficacy/performance endpoint, biological: Proportion of patients with at least one occurrence of resistant bacteria and yeasts in feces (among patients negative at baseline) [ Time Frame: up to 10 days after the end of FQs ]
    Duration of treatment with FQs ranges from 5 to 21 days, at the discretion of the Investigator
  • Efficacy/performance endpoint, biological: Proportion of patients with acquisition of intestinal colonization by C. difficile (among patients negative at baseline) [ Time Frame: up to 10 days after the end of FQs ]
    Duration of treatment with FQs ranges from 5 to 21 days, at the discretion of the Investigator
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Efficacy of DAV132 in Patients at High-Risk for Clostridium Difficile Infection (CDI)
Official Title  ICMJE A European Multicenter, Randomized, Parallel-group Study to Evaluate the Safety and Efficacy/Performance of DAV132 in Hospitalized Patients at High Risk for Clostridium Difficile Infection and Who Receive Fluoroquinolones for the Treatment of Acute Infections
Brief Summary The purpose of this study is to determine the safe use and evaluate the efficacy/performance of DAV132 in hospitalized patients at high risk for Clostridium difficile infection (CDI) and who receive fluoroquinolones (FQs) for the treatment of acute infections or for prophylaxis of febrile neutropenia.
Detailed Description Da Volterra develops DAV132, a novel therapeutic option preserving the intestinal microbiota, to prevent potentially life-threatening conditions such as CDI or emergence of antibiotic-resistant bacteria. Prevention of CDI remains critical unmet need, especially for patients at high risk of developing such infection.
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE Clostridium Difficile Infection
Intervention  ICMJE Device: DAV132

DAV132:

  • Dosage: 15 g/day activated charcoal (22.5 g/day DAV132)
  • Route: Oral
  • Duration: duration of fluoroquinolone treatment + 2 days

DAV132 is regulated as a medical device in Europe and as a drug in the United States of America.

Study Arms  ICMJE
  • Experimental: DAV132 group
    Patients randomized to the DAV132 arm will be administered DAV132 concomitantly with fluoroquinolones.
    Intervention: Device: DAV132
  • No Intervention: No DAV132 group
    Patients randomized to the No DAV132 arm will receive only fluoroquinolones, according to local standard of care.
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 17, 2018)
260
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE August 9, 2019
Actual Primary Completion Date August 9, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria. Eligible patients for the study must meet ALL the following inclusion criteria:

  1. Male or female ≥18 years of age
  2. Hospitalized patients requiring a systemic antibiotic treatment for a proven or strongly suspected bacterial infection (lower respiratory tract infection [LRTI], complicated urinary tract infection [cUTI]) or prophylactic treatment of febrile neutropenia for neutropenic patient
  3. Patients who are intended to receive one of the following FQs: moxifloxacin, levofloxacin, or ciprofloxacin, by oral or parenteral route, for an intended duration of 5 days (minimum) to 21 days (maximum), in monotherapy
  4. Patients expected to stay in hospital for at least 3 days after randomization
  5. Patients with the following conditions:

    - Previous history of CDI (no more than 2 episodes) within six months prior to study inclusion

    OR

    - Patient aged ≥65 years, and presenting with at least two of the following:

    • Previous cumulated exposure of at least 5 days to any antibiotics within the last 90 days
    • Patients who have at least one concurrent severe comorbidity among the following: malignant disease, chronic renal failure, cardiopulmonary condition (such as chronic congestive heart failure or severe arterial hypertension), diabetes mellitus, or liver cirrhosis
    • Previous hospitalization of more than 72h within the last 90 days, or patient receiving long-term nursing care for more than one month within the last 90 days
  6. Female patients participating in the study must be:

    - of non-childbearing potential: surgically sterilized at least 3 months prior to inclusion, or postmenopausal (menopause is defined as being aged >60 years, or aged between 45 and 60 years and being amenorrheic for ≥2 years)

    OR

    - of childbearing potential, and:

    • using an efficient double contraception from inclusion up to 24 hours after the end of the treatment period: hormonal contraception (including patch, contraceptive ring, etc.), intra-uterine device, or other mechanical contraception method

    AND

    condom, or diaphragm or cervical/vault cap, or spermicide

    AND

    must have a negative urine pregnancy test prior to inclusion to the study.

  7. Patients who have given their written informed consent prior to undertaking any study-related procedure.

Exclusion Criteria: Eligible patients for this study will be excluded if any of the following conditions are present:

  1. Antibacterial treatment within seven days before randomization
  2. Fluoroquinolone indication other than LRTI, cUTI, or febrile neutropenia prophylaxis
  3. Patients with suspected or diagnosed CDI at screening, and/or receiving a treatment effective against CDI
  4. Patients with diarrhea corresponding to Bristol stool chart types 5-7, combined with a stool frequency of at least three stools in 24 or fewer consecutive hours, regardless of its etiology
  5. Patients using probiotics for prevention of CDI and refusing to stop them at inclusion and during the study
  6. Patients currently taking activated charcoal
  7. Patients who have received a fecal microbial transplantation within the last 90 days prior to study screening
  8. A critically ill patient for whom transfer to an intensive care unit is scheduled, or patient who may likely have critical clinical deterioration within 48 hours;
  9. Patients with serious, uncontrolled disease, including but not limited to neutropenia expected to last >7 days (Investigator discretion) or with an estimated life expectancy shorter than 6 months
  10. Patients diagnosed with any cancer requiring taxane-based chemotherapy
  11. Patients with digestive stoma, known conditions at risk for intestinal obstruction, or known achlorhydria
  12. Contra-indication to oral therapy (eg, severe nausea/vomiting or ileus) or patient having tube feeding
  13. Patients unable or expected to be unable within 48 hours to receive a medication by oral route administration
  14. Known hypersensitivity to the activated charcoal, or to any of the constituents or excipients of DAV132
  15. Patients taking any drug/medication acting on (eg, metronidazole; sulfasalazine) or absorbed in the colon.
  16. Female patients planning a pregnancy, pregnant or breastfeeding
  17. Patients already included into this study
  18. Patients in an exclusion period of a previous study
  19. Patients with any social or logistical condition which in the opinion of the Investigator, may interfere with the conduct of the study, such as incapacity to understand well, not willing to collaborate, or cannot easily be contacted after discharge
  20. Patients not covered by a health insurance system where applicable and in compliance with the recommendations of the national laws in force relating to biomedical research.
  21. Patients under administrative or legal supervision.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Bulgaria,   Germany,   Romania,   Serbia
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03710694
Other Study ID Numbers  ICMJE DAV132-CL-2001
CIV-18-03-023465 ( Other Identifier: EUDAMED )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Da Volterra
Study Sponsor  ICMJE Da Volterra
Collaborators  ICMJE Syneos Health
Investigators  ICMJE
Principal Investigator: Maria J.G.T Vehreschild, MD Universitaetsklinikum Frankfurt
PRS Account Da Volterra
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP