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

NCT03710694 | Completed

• 2 other identifiers: DAV132-CL-2001CIV-18-03-023465
• Study Type: interventional
• Target: 260
• Locations: 4 countries
• Sites: 29

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.

Conditions

Clostridium Difficile Infection

Outcome Measures

Primary Outcomes (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).

  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.

  51 days after randomization

Secondary Outcomes (11)

• 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 CDI

  51 days after randomization

• Efficacy/performance endpoint, clinical: Proportion of patients with AAD

  51 days after randomization

• Efficacy/performance endpoint, clinical: Plasma levels of FQs

  Day 4

• Efficacy/performance endpoint, biological: Level of free fecal concentrations of FQs

  Day 1, Day 4, Day 6, 10 days after the end of FQs

Study Arms (2)

DAV132 group

EXPERIMENTAL

Patients randomized to the DAV132 arm will be administered DAV132 concomitantly with fluoroquinolones.

Device: DAV132

No DAV132 group

NO INTERVENTION

Patients randomized to the No DAV132 arm will receive only fluoroquinolones, according to local standard of care.

Interventions

DAV132 DEVICE

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.

DAV132 group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female ≥18 years of age
• 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
• 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
• Patients expected to stay in hospital for at least 3 days after randomization
• Patients with the following conditions:
• \- 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
• Female patients participating in the study must be:
• \- of childbearing potential, and:
• AND
• condom, or diaphragm or cervical/vault cap, or spermicide
• AND
• Patients who have given their written informed consent prior to undertaking any study-related procedure.

You may not qualify if:

• 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 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

Sponsors & Collaborators

• Da Volterra: lead
• Syneos Health: collaborator

Study Sites (29)

Multiprofile Hospital for Active Treatment Sveti Ivan Rilski - Kozloduy EOOD Internal Department

Kozloduy, 3320, Bulgaria

Location

MHAT "Dr Nikola Vasilev " AD 1

Kyustendil, 2500, Bulgaria

Location

MHAT "Dr. Stamen Iliev" AD 4

Montana, 3400, Bulgaria

Location

Pernik EOOD Specialized Hospital for Active Treatment of Pulmonary Diseases - Phthisiatry Department

Pernik, 2300, Bulgaria

Location

Hosp Ruse EOOD

Rousse, 7002, Bulgaria

Location

Multiprofile Hospital for Active Treatment Silistra AD Department of pneumology and phtisiatry

Silistra, 7500, Bulgaria

Location

Military Medical Academy, Clinic of Infectious Diseases

Sofia, 1606, Bulgaria

Location

UMHATEM N.I.Pirogov Department of internal diseases Clinic of internal diseases

Sofia, 1606, Bulgaria

Location

MHAT Sv. Anna Clinic of Urology

Varna, 9200, Bulgaria

Location

Universitätskliniken Köln (AöR) Klinik I für Innere Medizin

Cologne, 50937, Germany

Location

Universitaetsklinikum Frankfurt, Medizinische Klinik II

Frankfurt am Main, 60590, Germany

Location

Universitaetsklinikum Jena Klinik für Innere Medizin IV

Jena, 07747, Germany

Location

Medizinische Universitaetsklinik Abteilung Innere Medizin I

Tübingen, 72076, Germany

Location

Institutului Clinic Fundeni, Secţia Clinica Urologie III

Bucharest, 22328, Romania

Location

Spitalul Clinic de Boli Infecţioase şi Tropicale Dr. Victor Babeş, Secţia Pneumologie II

Bucharest, 30303, Romania

Location

Spitalului de Boli Infectioase si Tropicale "Dr. Victor Babes" Sectia Clinica de Boli Infectioase si Tropicale VI - adult

Bucharest, 30303, Romania

Location

Institutul de Pneumoftiziologie "MariusNasta" (Pavilionul IV), Sectia Pneumologie VII

Bucharest, 40206, Romania

Location

The Oncology Institute "Prof. Dr. Ion Chiricuţă"

Cluj-Napoca, 400015, Romania

Location

Spitalul Clinic de Pneumoftiziologie "Leon Daniello" Cluj-Napoca, Secţia Clinică Pneumologie I

Cluj-Napoca, 400371, Romania

Location

Spitalul Clinic de Boli Infecţioase si Pneumoftiziologie Victor Babeş Craiova, Secţia Boli Infecţioase Adulţi II

Craiova, 200515, Romania

Location

Spitalului Universitar de Urgenta Elias, Clinica Universitara de Geriatrie, Gerontologie si Psihogeriatrie, Sos. Bucuresti-Ploiesti

Otopeni, 13686, Romania

Location

Spitalul Clinic de Boli Infecţioase si Pneumoftiziologie "Dr. Victor Babeş" Timişoara, Clinica II Pneumologie

Timișoara, 300310, Romania

Location

Spitalului Clinic de Boli Infecţioase şi Pneumoftiziologie "Dr. Victor Babeş", Secţia Pneumologie II

Timișoara, 300310, Romania

Location

Spitalului Clinic Judeţean de Urgenţă "Pius Brînzeu" Timişoara, Secţia Clinică Urologie

Timișoara, 300736, Romania

Location

Clinical Hospital Centre Bezanijska Kosa Pulmonology Department

Belgrade, 11080, Serbia

Location

General Hospital Department for Lung Diseases and Tuberculosis

Čačak, 32000, Serbia

Location

Clinical Centre Kragujevac Clinic for Infectious Diseases

Kragujevac, 34000, Serbia

Location

Clinical Centre of Nis Clinic for Lung Diseases

Niš, 18000, Serbia

Location

Health Centre Uzice Department for Lung Diseases and Tuberculosis

Užice, 31000, Serbia

Location

Related Publications (4)

• de Gunzburg J, Ducher A, Modess C, Wegner D, Oswald S, Dressman J, Augustin V, Feger C, Andremont A, Weitschies W, Siegmund W. Targeted adsorption of molecules in the colon with the novel adsorbent-based medicinal product, DAV132: A proof of concept study in healthy subjects. J Clin Pharmacol. 2015 Jan;55(1):10-6. doi: 10.1002/jcph.359. Epub 2014 Jul 16.

  PMID: 25042595 BACKGROUND

• de Gunzburg J, Ghozlane A, Ducher A, Le Chatelier E, Duval X, Ruppe E, Armand-Lefevre L, Sablier-Gallis F, Burdet C, Alavoine L, Chachaty E, Augustin V, Varastet M, Levenez F, Kennedy S, Pons N, Mentre F, Andremont A. Protection of the Human Gut Microbiome From Antibiotics. J Infect Dis. 2018 Jan 30;217(4):628-636. doi: 10.1093/infdis/jix604.

  PMID: 29186529 BACKGROUND

• Burdet C, Sayah-Jeanne S, Nguyen TT, Hugon P, Sablier-Gallis F, Saint-Lu N, Corbel T, Ferreira S, Pulse M, Weiss W, Andremont A, Mentre F, de Gunzburg J. Antibiotic-Induced Dysbiosis Predicts Mortality in an Animal Model of Clostridium difficile Infection. Antimicrob Agents Chemother. 2018 Sep 24;62(10):e00925-18. doi: 10.1128/AAC.00925-18. Print 2018 Oct.

  PMID: 30061286 BACKGROUND

• Burdet C, Sayah-Jeanne S, Nguyen TT, Miossec C, Saint-Lu N, Pulse M, Weiss W, Andremont A, Mentre F, de Gunzburg J. Protection of Hamsters from Mortality by Reducing Fecal Moxifloxacin Concentration with DAV131A in a Model of Moxifloxacin-Induced Clostridium difficile Colitis. Antimicrob Agents Chemother. 2017 Sep 22;61(10):e00543-17. doi: 10.1128/AAC.00543-17. Print 2017 Oct.

  PMID: 28739791 BACKGROUND

MeSH Terms

Conditions

Clostridium Infections

Condition Hierarchy (Ancestors)

Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Study Officials

• Maria J.G.T Vehreschild, MD

  Universitaetsklinikum Frankfurt

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 9, 2018
• First Posted: October 18, 2018
• Study Start: October 31, 2018
• Primary Completion: August 9, 2019
• Study Completion: August 9, 2019
• Last Updated: August 30, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will not share

Locations

RO (11); DE (4); BU (9); SE (5)