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

NCT ID: NCT03710694

Last Updated: 2019-08-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

260 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-10-31

Study Completion Date

2019-08-09

Brief Summary

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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

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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.

Conditions

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Clostridium Difficile Infection

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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DAV132 group

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

Group Type EXPERIMENTAL

DAV132

Intervention Type 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.

No DAV132 group

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

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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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.

Intervention Type DEVICE

Eligibility Criteria

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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

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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Syneos Health

OTHER

Sponsor Role collaborator

Da Volterra

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Maria J.G.T Vehreschild, MD

Role: PRINCIPAL_INVESTIGATOR

Universitaetsklinikum Frankfurt

Locations

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

Kozloduy, , Bulgaria

Site Status

MHAT "Dr Nikola Vasilev " AD 1

Kyustendil, , Bulgaria

Site Status

MHAT "Dr. Stamen Iliev" AD 4

Montana, , Bulgaria

Site Status

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

Pernik, , Bulgaria

Site Status

Hosp Ruse EOOD

Rousse, , Bulgaria

Site Status

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

Silistra, , Bulgaria

Site Status

Military Medical Academy, Clinic of Infectious Diseases

Sofia, , Bulgaria

Site Status

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

Sofia, , Bulgaria

Site Status

MHAT Sv. Anna Clinic of Urology

Varna, , Bulgaria

Site Status

Universitätskliniken Köln (AöR) Klinik I für Innere Medizin

Cologne, , Germany

Site Status

Universitaetsklinikum Frankfurt, Medizinische Klinik II

Frankfurt am Main, , Germany

Site Status

Universitaetsklinikum Jena Klinik für Innere Medizin IV

Jena, , Germany

Site Status

Medizinische Universitaetsklinik Abteilung Innere Medizin I

Tübingen, , Germany

Site Status

Institutului Clinic Fundeni, Secţia Clinica Urologie III

Bucharest, , Romania

Site Status

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

Bucharest, , Romania

Site Status

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

Bucharest, , Romania

Site Status

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

Bucharest, , Romania

Site Status

The Oncology Institute "Prof. Dr. Ion Chiricuţă"

Cluj-Napoca, , Romania

Site Status

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

Cluj-Napoca, , Romania

Site Status

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

Craiova, , Romania

Site Status

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

Otopeni, , Romania

Site Status

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

Timișoara, , Romania

Site Status

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

Timișoara, , Romania

Site Status

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

Timișoara, , Romania

Site Status

Clinical Hospital Centre Bezanijska Kosa Pulmonology Department

Belgrade, , Serbia

Site Status

General Hospital Department for Lung Diseases and Tuberculosis

Čačak, , Serbia

Site Status

Clinical Centre Kragujevac Clinic for Infectious Diseases

Kragujevac, , Serbia

Site Status

Clinical Centre of Nis Clinic for Lung Diseases

Niš, , Serbia

Site Status

Health Centre Uzice Department for Lung Diseases and Tuberculosis

Užice, , Serbia

Site Status

Countries

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Bulgaria Germany Romania Serbia

References

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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.

Reference Type BACKGROUND
PMID: 25042595 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29186529 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30061286 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28739791 (View on PubMed)

Other Identifiers

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CIV-18-03-023465

Identifier Type: OTHER

Identifier Source: secondary_id

DAV132-CL-2001

Identifier Type: -

Identifier Source: org_study_id