Enterococcal BacteraemiaNCT04070820
Combination Treatment for Enterococcus Faecalis Bacteriemia Multicenter, Observational Study"
An observational study of Enterococcal Bacteraemia and Enterococcus Faecalis Infection, run by University of Bologna at 1 site in Italy.
Trial summary
Prospective, multicenter, observational study on the evaluation of efficacy of appropriate monotherapy vs combination treatment for non-complicated Enterococcus faecalis bloodstream infection (EF-BSI). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Enterococcal Bacteraemia, Enterococcus Faecalis Infection, Enterococcal Endocarditis
- How many people
- 500 participants
- Where
- 1 siteItaly
- Study dates
- 1 Sep 2019to Mar 2021
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: All consecutive, unselected patients with a first episode of monomicrobial EF-BSI will be screened for study inclusion
Who may be able to join
- Adult (>18 years)
- First monomicrobial EF-BSI
- Receipt of ≥ 5 days of at least one in vitro active drug (ampicillin, amoxicillin/clavulanate, ampicillin/sulbactam, piperacillin, vancomycin, teicoplanin, daptomycin and linezolid) with or without a synergistic drug (ceftriaxone, gentamycin, streptomycin), at common suggested dosages for EF-BSI in empirical or definitive therapy
- Written informed consent
Who cannot join
- Short term (within 3 days from BSI) mortality
- Other concomitant infection
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
Infectious Disease Unit - S.Orsola Malpighi Hospital
Bologna
Michele Bartoletti
About this study
Official title: "Combination Treatment for Enterococcus Faecalis Bacteremia: a Prospective, Multicenter, Observational Study"
Prospective, multicenter, observational study on the evaluation of efficacy of appropriate monotherapy vs combination treatment for non-complicated Enterococcus faecalis bloodstream infection (EF-BSI).
The aims of our study are:
Read more
Primary:
To compare the efficacy of appropriate monotherapy vs combination treatment for EF-BSI, according to standard of care.
Secondary:
- To compare the impact on clinical outcome of the initial combination therapy in the subgroup of patients with enterococcal endocarditis. In this case we will evaluate only the antibiotic treatment administered before the diagnosis of endocarditis assuming that any case of endocarditis will be treated with a combination therapy.
- To compare the efficacy of combination treatment (vs monotherapy) in the following subgroup of patients:
- Patients with low versus high risk of endocarditis according with the "Number of positive blood cultures, Origin of the bacteremia, previous Valve disease, Auscultation of heart murmur (NOVA) score".
- Patients with metastatic septic localizations. C. Patients with catheter-related BSI. D. Patients with indwelling cardiovascular device or prosthetic valve.
- To validate the NOVA score as a predictor of enterococcal endocarditis in a large multicentre cohort of patients with EF-BSI.
- To estimate optimal duration of treatment of EF-BSI in patients without endocarditis.
- To evaluate the rate of 90-day development of Clostridium difficile infection.
The promoting center is S. Orsola-Malpighi Hospital is a 1,420-bed tertiary care University Hospital in Bologna with an average of 72,000 admissions per year. A dedicate team of Infectious Diseases (ID) specialists is active in the promoting center. Investigators of this team have already coordinated multicenter studies on infections topics. Centers from other countries will be invited to participate by email, they will be ask to fulfil an agreement form.
All consecutive, unselected patients with monomicrobial EF-BSI will be screened for study inclusion. We expect to enroll about 500 patients.
Period of data collection will be from september 2019 to 31th December 2020.
- Conditions
- Enterococcal Bacteraemia, Enterococcus Faecalis Infection, Enterococcal Endocarditis, Bloodstream Infection
- Keywords
- Combination therapy, Bloodstream Infection, Enterococcus faecalis Infection, Endocarditis
- Medical subject headings
- Sepsis, Endocarditis
What is being measured
The primary outcome is the main question the study is designed to answer.
Survival
Patient alive
Measured: End of Treatment, at least 2 weeks from first negative follow-up bloodculture
Body temperature (Celsius degrees)
Fever resolution
Measured: End of Treatment, at least 2 weeks from first negative follow-up bloodculture
Sequential Organ Failure Assessment (SOFA) Score
Stable or improved SOFA score. Total SOFA score ranges from 0 to 24 points. Total SOFA score consist of the sum of individual score of following items: Respiratory System (PaO2/FiO2), Cardiovascular system (Mean Arterial Pressure or administration vasopressure required), Newrvous System (Glasgow Coma Scale), Liver (bilirubin), Coagulation (platelets), Kidneys (creatinine). Each items receive a score ranging from 0 to 4 pt.
Measured: End of Treatment, at least 2 weeks from first negative follow-up bloodculture
Blood cultures
Follow-up Blood cultures negative for E. faecalis
Measured: End of Treatment, at least 2 weeks from first negative follow-up bloodculture
Blood cultures
No relapse of EF-BSI
Measured: 90 days from End of Treatment
Antibiotic therapy
No need to modify initial therapy
Measured: 90 days from End of Treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Aug 2019
- Study start1 Sep 2019
- Primary completionMar 2021 (estimated)
- Study completionMar 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (21)Papers the sponsor has linked to this study.
- Other trials for Enterococcal BacteraemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 500 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Bologna
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Michele Bartoletti, University of Bologna
- Investigators
- Michele Bartoletti, Principal investigator, Dipartimento di Scienze mediche e chirurgiche, Alma Mater-University of Bologna
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04070820
- Sponsor's protocol ID
- EfFAECT
- Status last verified
- Mar 2020
- First submitted
- 22 Aug 2019
- Last updated
- 25 Mar 2020
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Wisplinghoff H, Bischoff T, Tallent SM, Seifert H, Wenzel RP, Edmond MB. Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study. Clin Infect Dis. 2004 Aug 1;39(3):309-17. doi: 10.1086/421946. Epub 2004 Jul 15.
PubMed 15306996Rodriguez-Bano J, Lopez-Prieto MD, Portillo MM, Retamar P, Natera C, Nuno E, Herrero M, del Arco A, Munoz A, Tellez F, Torres-Tortosa M, Martin-Aspas A, Arroyo A, Ruiz A, Moya R, Corzo JE, Leon L, Perez-Lopez JA; SAEI/SAMPAC Bacteraemia Group. Epidemiology and clinical features of community-acquired, healthcare-associated and nosocomial bloodstream infections in tertiary-care and community hospitals. Clin Microbiol Infect. 2010 Sep;16(9):1408-13. doi: 10.1111/j.1469-0691.2009.03089.x.
PubMed 19845694Cahill TJ, Prendergast BD. Infective endocarditis. Lancet. 2016 Feb 27;387(10021):882-93. doi: 10.1016/S0140-6736(15)00067-7. Epub 2015 Sep 1.
PubMed 26341945Reigadas E, Rodriguez-Creixems M, Guembe M, Sanchez-Carrillo C, Martin-Rabadan P, Bouza E. Catheter-related bloodstream infection caused by Enterococcus spp. Clin Microbiol Infect. 2013 May;19(5):457-61. doi: 10.1111/j.1469-0691.2012.03897.x. Epub 2012 May 22.
PubMed 22612464Chirouze C, Athan E, Alla F, Chu VH, Ralph Corey G, Selton-Suty C, Erpelding ML, Miro JM, Olaison L, Hoen B; International Collaboration on Endocarditis Study Group. Enterococcal endocarditis in the beginning of the 21st century: analysis from the International Collaboration on Endocarditis-Prospective Cohort Study. Clin Microbiol Infect. 2013 Dec;19(12):1140-7. doi: 10.1111/1469-0691.12166. Epub 2013 Mar 20.
PubMed 23517406McBride SJ, Upton A, Roberts SA. Clinical characteristics and outcomes of patients with vancomycin-susceptible Enterococcus faecalis and Enterococcus faecium bacteraemia--a five-year retrospective review. Eur J Clin Microbiol Infect Dis. 2010 Jan;29(1):107-14. doi: 10.1007/s10096-009-0830-5. Epub 2009 Nov 15.
PubMed 19916034Gray J, Marsh PJ, Stewart D, Pedler SJ. Enterococcal bacteraemia: a prospective study of 125 episodes. J Hosp Infect. 1994 Jul;27(3):179-86. doi: 10.1016/0195-6701(94)90125-2.
PubMed 7963458Suppli M, Aabenhus R, Harboe ZB, Andersen LP, Tvede M, Jensen JU. Mortality in enterococcal bloodstream infections increases with inappropriate antimicrobial therapy. Clin Microbiol Infect. 2011 Jul;17(7):1078-83. doi: 10.1111/j.1469-0691.2010.03394.x. Epub 2010 Dec 3.
PubMed 20946408Foo H, Chater M, Maley M, van Hal SJ. Glycopeptide use is associated with increased mortality in Enterococcus faecalis bacteraemia--authors' response. J Antimicrob Chemother. 2014 Nov;69(11):3166. doi: 10.1093/jac/dku329. Epub 2014 Aug 12. No abstract available.
PubMed 25118271Cheah AL, Spelman T, Liew D, Peel T, Howden BP, Spelman D, Grayson ML, Nation RL, Kong DC. Enterococcal bacteraemia: factors influencing mortality, length of stay and costs of hospitalization. Clin Microbiol Infect. 2013 Apr;19(4):E181-9. doi: 10.1111/1469-0691.12132. Epub 2013 Feb 7.
PubMed 23398607Mermel LA, Allon M, Bouza E, Craven DE, Flynn P, O'Grady NP, Raad II, Rijnders BJ, Sherertz RJ, Warren DK. Clinical practice guidelines for the diagnosis and management of intravascular catheter-related infection: 2009 Update by the Infectious Diseases Society of America. Clin Infect Dis. 2009 Jul 1;49(1):1-45. doi: 10.1086/599376.
PubMed 19489710Murray BE. The life and times of the Enterococcus. Clin Microbiol Rev. 1990 Jan;3(1):46-65. doi: 10.1128/CMR.3.1.46.
PubMed 2404568Gavalda J, Len O, Miro JM, Munoz P, Montejo M, Alarcon A, de la Torre-Cisneros J, Pena C, Martinez-Lacasa X, Sarria C, Bou G, Aguado JM, Navas E, Romeu J, Marco F, Torres C, Tornos P, Planes A, Falco V, Almirante B, Pahissa A. Brief communication: treatment of Enterococcus faecalis endocarditis with ampicillin plus ceftriaxone. Ann Intern Med. 2007 Apr 17;146(8):574-9. doi: 10.7326/0003-4819-146-8-200704170-00008.
PubMed 17438316Maki DG, Agger WA. Enterococcal bacteremia: clinical features, the risk of endocarditis, and management. Medicine (Baltimore). 1988 Jul;67(4):248-69.
PubMed 3134590Sandoe JA, Witherden IR, Au-Yeung HK, Kite P, Kerr KG, Wilcox MH. Enterococcal intravascular catheter-related bloodstream infection: management and outcome of 61 consecutive cases. J Antimicrob Chemother. 2002 Oct;50(4):577-82. doi: 10.1093/jac/dkf182.
PubMed 12356804
Study at a glance
From the registry record, last updated by the sponsor on 25 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- "Combination Treatment for Enterococcus Faecalis Bacteremia: a Prospective, Multicenter, Observational Study"
- ClinicalTrials.gov ID
- NCT04070820
- Acronym / sponsor ID
- EfFAECT
- Conditions
- Enterococcal Bacteraemia, Enterococcus Faecalis Infection, Enterococcal Endocarditis, Bloodstream Infection
- Keywords
- Combination therapy, Bloodstream Infection, Enterococcus faecalis Infection, Endocarditis
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 500 participants (estimated)
- Lead sponsor
- University of BolognaUniversity, hospital or other
- Study start
- 1 Sep 2019 (actual)
- Primary completion
- Mar 2021 (estimated)
- Study completion
- Mar 2021 (estimated)
- First posted
- 28 Aug 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Prospective, multicenter, observational study on the evaluation of efficacy of appropriate monotherapy vs combination treatment for non-complicated Enterococcus faecalis bloodstream infection (EF-BSI).
The aims of our study are:
Primary:
To compare the efficacy of appropriate monotherapy vs combination treatment for EF-BSI, according to standard of care.
Secondary:
- To compare the impact on clinical outcome of the initial combination therapy in the subgroup of patients with enterococcal endocarditis. In this case we will evaluate only the antibiotic treatment administered before the diagnosis of endocarditis assuming that any case of endocarditis will be treated with a combination therapy.
- To compare the efficacy of combination treatment (vs monotherapy) in the following subgroup of patients:
- Patients with low versus high risk of endocarditis according with the "Number of positive blood cultures, Origin of the bacteremia, previous Valve disease, Auscultation of heart murmur (NOVA) score".
- Patients with metastatic septic localizations. C. Patients with catheter-related BSI. D. Patients with indwelling cardiovascular device or prosthetic valve.
- To validate the NOVA score as a predictor of enterococcal endocarditis in a large multicentre cohort of patients with EF-BSI.
- To estimate optimal duration of treatment of EF-BSI in patients without endocarditis.
- To evaluate the rate of 90-day development of Clostridium difficile infection.
The promoting center is S. Orsola-Malpighi Hospital is a 1,420-bed tertiary care University Hospital in Bologna with an average of 72,000 admissions per year. A dedicate team of Infectious Diseases (ID) specialists is active in the promoting center. Investigators of this team have already coordinated multicenter studies on infections topics. Centers from other countries will be invited to participate by email, they will be ask to fulfil an agreement form.
All consecutive, unselected patients with monomicrobial EF-BSI will be screened for study inclusion. We expect to enroll about 500 patients.
Period of data collection will be from september 2019 to 31th December 2020.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- All consecutive, unselected patients with a first episode of monomicrobial EF-BSI will be screened for study inclusion
Key inclusion criteria (4 listed)
- Adult (>18 years)
- First monomicrobial EF-BSI
- Receipt of ≥ 5 days of at least one in vitro active drug (ampicillin, amoxicillin/clavulanate, ampicillin/sulbactam, piperacillin, vancomycin, teicoplanin, daptomycin and linezolid) with or without a synergistic drug (ceftriaxone, gentamycin, streptomycin), at common suggested dosages for EF-BSI in empirical or definitive therapy
- Written informed consent
Key exclusion criteria (2 listed)
- Short term (within 3 days from BSI) mortality
- Other concomitant infection
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Survival
Time frame: End of Treatment, at least 2 weeks from first negative follow-up bloodculture
Patient alive
Body temperature (Celsius degrees)
Time frame: End of Treatment, at least 2 weeks from first negative follow-up bloodculture
Fever resolution
Sequential Organ Failure Assessment (SOFA) Score
Time frame: End of Treatment, at least 2 weeks from first negative follow-up bloodculture
Stable or improved SOFA score. Total SOFA score ranges from 0 to 24 points. Total SOFA score consist of the sum of individual score of following items: Respiratory System (PaO2/FiO2), Cardiovascular system (Mean Arterial Pressure or administration vasopressure required), Newrvous System (Glasgow Coma Scale), Liver (bilirubin), Coagulation (platelets), Kidneys (creatinine). Each items receive a score ranging from 0 to 4 pt.
Blood cultures
Time frame: End of Treatment, at least 2 weeks from first negative follow-up bloodculture
Follow-up Blood cultures negative for E. faecalis
Blood cultures
Time frame: 90 days from End of Treatment
No relapse of EF-BSI
Antibiotic therapy
Time frame: 90 days from End of Treatment
No need to modify initial therapy
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Mar 2020.
- Background: PubMed 15306996Wisplinghoff H, Bischoff T, Tallent SM, Seifert H, Wenzel RP, Edmond MB. Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study. Clin Infect Dis. 2004 Aug 1;39(3):309-17. doi: 10.1086/421946. Epub 2004 Jul 15.
- Background: PubMed 19845694Rodriguez-Bano J, Lopez-Prieto MD, Portillo MM, Retamar P, Natera C, Nuno E, Herrero M, del Arco A, Munoz A, Tellez F, Torres-Tortosa M, Martin-Aspas A, Arroyo A, Ruiz A, Moya R, Corzo JE, Leon L, Perez-Lopez JA; SAEI/SAMPAC Bacteraemia Group. Epidemiology and clinical features of community-acquired, healthcare-associated and nosocomial bloodstream infections in tertiary-care and community hospitals. Clin Microbiol Infect. 2010 Sep;16(9):1408-13. doi: 10.1111/j.1469-0691.2009.03089.x.
- Background: PubMed 26341945Cahill TJ, Prendergast BD. Infective endocarditis. Lancet. 2016 Feb 27;387(10021):882-93. doi: 10.1016/S0140-6736(15)00067-7. Epub 2015 Sep 1.
- Background: PubMed 22612464Reigadas E, Rodriguez-Creixems M, Guembe M, Sanchez-Carrillo C, Martin-Rabadan P, Bouza E. Catheter-related bloodstream infection caused by Enterococcus spp. Clin Microbiol Infect. 2013 May;19(5):457-61. doi: 10.1111/j.1469-0691.2012.03897.x. Epub 2012 May 22.
- Background: PubMed 23517406Chirouze C, Athan E, Alla F, Chu VH, Ralph Corey G, Selton-Suty C, Erpelding ML, Miro JM, Olaison L, Hoen B; International Collaboration on Endocarditis Study Group. Enterococcal endocarditis in the beginning of the 21st century: analysis from the International Collaboration on Endocarditis-Prospective Cohort Study. Clin Microbiol Infect. 2013 Dec;19(12):1140-7. doi: 10.1111/1469-0691.12166. Epub 2013 Mar 20.
- Background: PubMed 19916034McBride SJ, Upton A, Roberts SA. Clinical characteristics and outcomes of patients with vancomycin-susceptible Enterococcus faecalis and Enterococcus faecium bacteraemia--a five-year retrospective review. Eur J Clin Microbiol Infect Dis. 2010 Jan;29(1):107-14. doi: 10.1007/s10096-009-0830-5. Epub 2009 Nov 15.
- Background: PubMed 7963458Gray J, Marsh PJ, Stewart D, Pedler SJ. Enterococcal bacteraemia: a prospective study of 125 episodes. J Hosp Infect. 1994 Jul;27(3):179-86. doi: 10.1016/0195-6701(94)90125-2.
- Background: PubMed 20946408Suppli M, Aabenhus R, Harboe ZB, Andersen LP, Tvede M, Jensen JU. Mortality in enterococcal bloodstream infections increases with inappropriate antimicrobial therapy. Clin Microbiol Infect. 2011 Jul;17(7):1078-83. doi: 10.1111/j.1469-0691.2010.03394.x. Epub 2010 Dec 3.
- Background: PubMed 25118271Foo H, Chater M, Maley M, van Hal SJ. Glycopeptide use is associated with increased mortality in Enterococcus faecalis bacteraemia--authors' response. J Antimicrob Chemother. 2014 Nov;69(11):3166. doi: 10.1093/jac/dku329. Epub 2014 Aug 12. No abstract available.
- Background: PubMed 23398607Cheah AL, Spelman T, Liew D, Peel T, Howden BP, Spelman D, Grayson ML, Nation RL, Kong DC. Enterococcal bacteraemia: factors influencing mortality, length of stay and costs of hospitalization. Clin Microbiol Infect. 2013 Apr;19(4):E181-9. doi: 10.1111/1469-0691.12132. Epub 2013 Feb 7.
- Background: PubMed 19489710Mermel LA, Allon M, Bouza E, Craven DE, Flynn P, O'Grady NP, Raad II, Rijnders BJ, Sherertz RJ, Warren DK. Clinical practice guidelines for the diagnosis and management of intravascular catheter-related infection: 2009 Update by the Infectious Diseases Society of America. Clin Infect Dis. 2009 Jul 1;49(1):1-45. doi: 10.1086/599376.
- Background: PubMed 2404568Murray BE. The life and times of the Enterococcus. Clin Microbiol Rev. 1990 Jan;3(1):46-65. doi: 10.1128/CMR.3.1.46.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michele Bartoletti principal investigator
Dipartimento di Scienze mediche e chirurgiche, Alma Mater-University of Bologna
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Enterococcal Bacteraemia and Enterococcus Faecalis Infection, run by University of Bologna at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 25 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Michele Bartoletti (0512143199, m.bartoletti@unibo.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Survival (time frame: End of Treatment, at least 2 weeks from first negative follow-up bloodculture). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04070820, which also lists 21 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Mar 2020; AzTrials last refreshed its copy on 29 Oct 2026.