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

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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

Study Description
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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.

Condition or disease Intervention/treatment Phase
Clostridium Difficile Infection Device: DAV132 Not Applicable

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 Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 260 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: 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
Actual Study Start Date : October 31, 2018
Actual Primary Completion Date : August 9, 2019
Actual Study Completion Date : August 9, 2019
Arms and Interventions
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Arm Intervention/treatment
Experimental: DAV132 group
Patients randomized to the DAV132 arm will be administered DAV132 concomitantly with fluoroquinolones.
 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.
No Intervention: No DAV132 group
Patients randomized to the No DAV132 arm will receive only fluoroquinolones, according to local standard of care.


Outcome Measures
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Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. Safety endpoint: Number of AEs and proportion of patients with at least one AE [ Time Frame: 51 days after randomization ]
  2. Efficacy/performance endpoint, clinical:Proportion of patients with CDI [ Time Frame: 51 days after randomization ]
  3. Efficacy/performance endpoint, clinical: Proportion of patients with AAD [ Time Frame: 51 days after randomization ]
  4. Efficacy/performance endpoint, clinical: Plasma levels of FQs [ Time Frame: Day 4 ]
  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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


Eligibility Criteria
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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. 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.
Contacts and Locations
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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): NCT03710694


Locations
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Sponsors and Collaborators
Da Volterra
Syneos Health
Investigators
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Principal Investigator: Maria J.G.T Vehreschild, MD Universitaetsklinikum Frankfurt
More Information
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Publications:

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Responsible Party: Da Volterra
ClinicalTrials.gov Identifier: NCT03710694    
Other Study ID Numbers: DAV132-CL-2001
CIV-18-03-023465 ( Other Identifier: EUDAMED )
First Posted: October 18, 2018    Key Record Dates
Last Update Posted: August 30, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Infection
Communicable Diseases
Clostridium Infections
Enterocolitis, Pseudomembranous
Gram-Positive Bacterial Infections
Bacterial Infections
 Enterocolitis
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases