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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 : Recruiting
First Posted : October 18, 2018
Last Update Posted : November 16, 2018
Sponsor:
Collaborator:
Syneos Health
Information provided by (Responsible Party):
Da Volterra

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 Type : Interventional  (Clinical Trial)
Estimated 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
Estimated Primary Completion Date : June 8, 2019
Estimated Study Completion Date : June 8, 2019

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.



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



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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.

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


Contacts
Contact: Marie-Noëlle Bouverne +33 1 58 39 32 20 marie-noelle.bouverne@davolterra.com
Contact: Marina Varastet +33 1 58 39 32 20 marina.varastet@davolterra.com

Locations
Bulgaria
Multiprofile Hospital for Active Treatment Sveti Ivan Rilski - Kozloduy EOOD Internal Department Not yet recruiting
Kozloduy, Bulgaria, 3320
Contact: Rumen Tiholov         
MHAT "Dr Nikola Vasilev " AD 1 Not yet recruiting
Kyustendil, Bulgaria, 2500
Contact: Sashka Pavlova         
MHAT "Dr. Stamen Iliev" AD 4 Not yet recruiting
Montana, Bulgaria, 3400
Contact: Lidiya Nikolcheva-Todorova         
Pernik EOOD Specialized Hospital for Active Treatment of Pulmonary Diseases - Phthisiatry Department Not yet recruiting
Pernik, Bulgaria, 2300
Contact: Galina Petrova         
Hosp Ruse EOOD Not yet recruiting
Ruse, Bulgaria, 7002
Contact: Hristo Metev         
Multiprofile Hospital for Active Treatment Silistra AD Department of pneumology and phtisiatry Not yet recruiting
Silistra, Bulgaria, 7500
Contact: Mirena Sapundzhieva         
Military Medical Academy, Clinic of Infectious Diseases Not yet recruiting
Sofia, Bulgaria, 1606
Contact: Georgi Popov         
UMHATEM N.I.Pirogov Department of internal diseases Clinic of internal diseases Not yet recruiting
Sofia, Bulgaria, 1606
Contact: Diana Slaveva Mladenova         
MHAT Sv. Anna Clinic of Urology Not yet recruiting
Varna, Bulgaria, 9200
Contact: Boyan Lazarov         
Germany
Universitaetsklinikum Jena Klinik für Innere Medizin IV Not yet recruiting
Jena, Germany, 07747
Contact: Philipp Reuken         
Universitätskliniken Köln (AöR) Klinik I für Innere Medizin Not yet recruiting
Köln, Germany, 50937
Contact: Maria Vehreschild         
Medizinische Universitaetsklinik Abteilung Innere Medizin I Not yet recruiting
Tuebingen, Germany, 72076
Contact: Christoph Berg         
Romania
Institutului Clinic Fundeni, Secţia Clinica Urologie III Not yet recruiting
Bucuresti, Romania, 22328
Contact: Robert Ionut Stoica         
Spitalul Clinic de Boli Infecţioase şi Tropicale Dr. Victor Babeş, Secţia Pneumologie II Not yet recruiting
Bucuresti, Romania, 30303
Contact: Ana Maria Trăilescu         
Spitalului de Boli Infectioase si Tropicale "Dr. Victor Babes" Sectia Clinica de Boli Infectioase si Tropicale VI - adult Not yet recruiting
Bucuresti, Romania, 30303
Contact: Simin-Aysel Florescu         
Institutul de Pneumoftiziologie "MariusNasta" (Pavilionul IV), Sectia Pneumologie VII Not yet recruiting
Bucuresti, Romania, 40206
Contact: Dragos Zaharia         
The Oncology Institute "Prof. Dr. Ion Chiricuţă" Not yet recruiting
Cluj-Napoca, Romania, 400015
Contact: Delia Herghea         
Spitalul Clinic de Pneumoftiziologie "Leon Daniello" Cluj-Napoca, Secţia Clinică Pneumologie I Not yet recruiting
Cluj-Napoca, Romania, 400371
Contact: Manuela Cosmina Magdau         
Spitalul Clinic de Boli Infecţioase si Pneumoftiziologie Victor Babeş Craiova, Secţia Boli Infecţioase Adulţi II Not yet recruiting
Craiova, Romania, 200515
Contact: Gheorge Iulian Diaconescu         
Spitalului Universitar de Urgenta Elias, Clinica Universitara de Geriatrie, Gerontologie si Psihogeriatrie, Sos. Bucuresti-Ploiesti Not yet recruiting
Otopeni, Romania, 13686
Contact: Luiza Spiru         
Spitalul Clinic de Boli Infecţioase si Pneumoftiziologie "Dr. Victor Babeş" Timişoara, Clinica II Pneumologie Not yet recruiting
Timişoara, Romania, 300310
Contact: Stefan Mihaicuta         
Spitalului Clinic de Boli Infecţioase şi Pneumoftiziologie "Dr. Victor Babeş", Secţia Pneumologie II Not yet recruiting
Timişoara, Romania, 300310
Contact: Monica Marc         
Spitalului Clinic Judeţean de Urgenţă "Pius Brînzeu" Timişoara, Secţia Clinică Urologie Not yet recruiting
Timişoara, Romania, 300736
Contact: Razvan Bardan         
Serbia
Clinical Hospital Centre Bezanijska Kosa Pulmonology Department Recruiting
Belgrad, Serbia, 11080
Contact: Vojislav Radosavljevic         
Clinical Centre Kragujevac Clinic for Infectious Diseases Recruiting
Kragujevac, Serbia, 34000
Contact: Olgica Gajovic         
Clinical Centre of Nis Clinic for Lung Diseases Recruiting
Niš, Serbia, 18000
Contact: Desa Nastasijevic-Borovac         
Health Centre Uzice Department for Lung Diseases and Tuberculosis Recruiting
Užice, Serbia, 31000
Contact: Zorica Radojevic         
General Hospital Department for Lung Diseases and Tuberculosis Recruiting
Čačak, Serbia, 32000
Contact: Julijana Antonovic         
Sponsors and Collaborators
Da Volterra
Syneos Health
Investigators
Principal Investigator: Maria J.G.T Vehreschild, MD Uniklinik Köln

Publications:
Responsible Party: Da Volterra
ClinicalTrials.gov Identifier: NCT03710694     History of Changes
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: November 16, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Infection
Communicable Diseases
Fluoroquinolones
Anti-Bacterial Agents
Anti-Infective Agents
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action