Safety and Efficacy of DAV132 in Patients at High-Risk for Clostridium Difficile Infection (CDI)
- Conditions
- Clostridium Difficile Infection
- Interventions
- Device: DAV132
- Registration Number
- NCT03710694
- Lead Sponsor
- 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.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 260
Not provided
Eligible patients for this study will be excluded if any of the following conditions are present:
- Antibacterial treatment within seven days before randomization
- Fluoroquinolone indication other than LRTI, cUTI, or febrile neutropenia prophylaxis
- Patients with suspected or diagnosed CDI at screening, and/or receiving a treatment effective against CDI
- 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
- Patients using probiotics for prevention of CDI and refusing to stop them at inclusion and during the study
- Patients currently taking activated charcoal
- Patients who have received a fecal microbial transplantation within the last 90 days prior to study screening
- 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;
- 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
- Patients diagnosed with any cancer requiring taxane-based chemotherapy
- Patients with digestive stoma, known conditions at risk for intestinal obstruction, or known achlorhydria
- Contra-indication to oral therapy (eg, severe nausea/vomiting or ileus) or patient having tube feeding
- Patients unable or expected to be unable within 48 hours to receive a medication by oral route administration
- Known hypersensitivity to the activated charcoal, or to any of the constituents or excipients of DAV132
- Patients taking any drug/medication acting on (eg, metronidazole; sulfasalazine) or absorbed in the colon.
- Female patients planning a pregnancy, pregnant or breastfeeding
- Patients already included into this study
- Patients in an exclusion period of a previous study
- 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
- 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.
- Patients under administrative or legal supervision.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description DAV132 group DAV132 Patients randomized to the DAV132 arm will be administered DAV132 concomitantly with fluoroquinolones.
- Primary Outcome Measures
Name Time Method 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). 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
Name Time Method Safety endpoint: Number of AEs and proportion of patients with at least one AE 51 days after randomization Efficacy/performance endpoint, clinical: Proportion of patients with AAD 51 days after randomization Efficacy/performance endpoint, biological: Levels of β-diversity of the intestinal microbiota 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 acquisition of intestinal colonization by C. difficile (among patients negative at baseline) 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, clinical:Proportion of patients with CDI 51 days after randomization Efficacy/performance endpoint, biological: Level of free fecal concentrations of FQs 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 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: Proportion of patients with resistant bacteria and/or yeasts in feces 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) 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, clinical: Plasma levels of FQs Day 4 Efficacy/performance endpoint, biological: Change from D1 of α-diversity of the intestinal microbiota 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
Trial Locations
- Locations (29)
Spitalul Clinic de Boli Infecţioase şi Tropicale Dr. Victor Babeş, Secţia Pneumologie II
🇷🇴Bucuresti, Romania
Institutul de Pneumoftiziologie "MariusNasta" (Pavilionul IV), Sectia Pneumologie VII
🇷🇴Bucuresti, Romania
Hosp Ruse EOOD
🇧🇬Ruse, Bulgaria
Spitalului de Boli Infectioase si Tropicale "Dr. Victor Babes" Sectia Clinica de Boli Infectioase si Tropicale VI - adult
🇷🇴Bucuresti, Romania
Multiprofile Hospital for Active Treatment Silistra AD Department of pneumology and phtisiatry
🇧🇬Silistra, Bulgaria
Spitalul Clinic de Pneumoftiziologie "Leon Daniello" Cluj-Napoca, Secţia Clinică Pneumologie I
🇷🇴Cluj-Napoca, Romania
Military Medical Academy, Clinic of Infectious Diseases
🇧🇬Sofia, Bulgaria
Spitalul Clinic de Boli Infecţioase si Pneumoftiziologie Victor Babeş Craiova, Secţia Boli Infecţioase Adulţi II
🇷🇴Craiova, Romania
Multiprofile Hospital for Active Treatment Sveti Ivan Rilski - Kozloduy EOOD Internal Department
🇧🇬Kozloduy, Bulgaria
MHAT "Dr Nikola Vasilev " AD 1
🇧🇬Kyustendil, Bulgaria
Clinical Hospital Centre Bezanijska Kosa Pulmonology Department
🇷🇸Belgrad, Serbia
Universitätskliniken Köln (AöR) Klinik I für Innere Medizin
🇩🇪Köln, Germany
General Hospital Department for Lung Diseases and Tuberculosis
🇷🇸Čačak, Serbia
MHAT "Dr. Stamen Iliev" AD 4
🇧🇬Montana, Bulgaria
MHAT Sv. Anna Clinic of Urology
🇧🇬Varna, Bulgaria
Institutului Clinic Fundeni, Secţia Clinica Urologie III
🇷🇴Bucuresti, Romania
Pernik EOOD Specialized Hospital for Active Treatment of Pulmonary Diseases - Phthisiatry Department
🇧🇬Pernik, Bulgaria
The Oncology Institute "Prof. Dr. Ion Chiricuţă"
🇷🇴Cluj-Napoca, Romania
Spitalul Clinic de Boli Infecţioase si Pneumoftiziologie "Dr. Victor Babeş" Timişoara, Clinica II Pneumologie
🇷🇴Timişoara, Romania
UMHATEM N.I.Pirogov Department of internal diseases Clinic of internal diseases
🇧🇬Sofia, Bulgaria
Spitalului Universitar de Urgenta Elias, Clinica Universitara de Geriatrie, Gerontologie si Psihogeriatrie, Sos. Bucuresti-Ploiesti
🇷🇴Otopeni, Romania
Spitalului Clinic de Boli Infecţioase şi Pneumoftiziologie "Dr. Victor Babeş", Secţia Pneumologie II
🇷🇴Timişoara, Romania
Universitaetsklinikum Jena Klinik für Innere Medizin IV
🇩🇪Jena, Germany
Universitaetsklinikum Frankfurt, Medizinische Klinik II
🇩🇪Frankfurt am Main, Germany
Medizinische Universitaetsklinik Abteilung Innere Medizin I
🇩🇪Tuebingen, Germany
Clinical Centre Kragujevac Clinic for Infectious Diseases
🇷🇸Kragujevac, Serbia
Spitalului Clinic Judeţean de Urgenţă "Pius Brînzeu" Timişoara, Secţia Clinică Urologie
🇷🇴Timişoara, Romania
Clinical Centre of Nis Clinic for Lung Diseases
🇷🇸Niš, Serbia
Health Centre Uzice Department for Lung Diseases and Tuberculosis
🇷🇸Užice, Serbia