Gram-negative BacteremiaPhase 4GNB5NCT04291768
Shortened Antibiotic Treatment of 5 Days in Gram-negative Bacteremia
A Phase 4 study testing Shortened antibiotic treatment and Standard antibiotic treatment in people with Gram-negative Bacteremia and Urinary Tract Infection Bacterial, run by Thomas Benfield at 13 sites in Denmark.
Trial summary
GNB5 is an investigator-initiated multicentre non-inferiority randomized controlled trial which aims to assess the efficacy and safety of shortened antibiotic for patients hospitalized with a Gram negative bacteremia with a urinary tract source of infection (GNB). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Gram-negative Bacteremia, Urinary Tract Infection Bacterial
- What is being tested?
- Shortened antibiotic treatment and Standard antibiotic treatment
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 380 participants
- Where
- 13 sitesDenmark
- Study dates
- 11 Mar 2020to 1 Oct 2026
- Phase
- Phase 4
- 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
Who may be able to join
- Age >18 years
- Blood culture positive for Gram-negative bacteria
- Evidence of urinary tract source of infection (positive urine culture or at least one clinical symptom compatible with urinary tract infection)
- Antibiotic treatment with antimicrobial activity to Gram-negative bacteria administrated within 12 hours of first blood culture
- Temperature <37.8°C at randomization
- Clinically stabile at randomization (systolic blood pressure > 90 mm Hg, heart rate <100 beats/min., respiratory rate <24/minute, peripheral oxygen saturation > 90 %)
- Oral and written informed consent
Who cannot join
- Antibiotic treatment (>2 day) with antimicrobial activity to Gram-negative bacteria within 14 days of inclusion
- Gram-negative bacteremia within 30 days of blood culture
- Immunosuppression (Untreated HIV-infection, Neutropenia (absolute neutrophil count < 1.0 x 109/l), Untreated terminal cancer, Receiving immunosuppressive agents (ATC-code L04A), Corticosteroid treatment (≥20 mg/day prednisone or the equivalent for >14 days) within the last 30 days, Chemotherapy within the last 30 days, Immunosuppressed after solid organ transplantation, Asplenia)
- Polymicrobial growth in blood culture
- Bacteremia with non-fermenting Gram-negative bacteria (Acinetobacter spp, Burkholderia spp, Pseudomonas spp), Brucella spp, or Fusobacterium spp
- Failure to remove source of infection within 72 hours of first blood culture (e.g. change of catheter á demeure)
- Pregnancy or breastfeeding
Trial locations and contacts
13 sites in 1 country.
Thomas Benfield, MD DMSc contact
13 sites in 1 country
Denmark13 sites, 13 recruiting
- Not yet recruiting
University Hospital of Aalborg
Aalborg, 9000
Henrik Nielsen, MD DMSc, henrik.nielsen@rn.dk
- Not yet recruiting
University Hospital of Aarhus
Aarhus, 8200
Lars Østergaard, MD DMSc, larsoest@rm.dk
- Not yet recruiting
Rigshospitalet
Copenhagen, 2100
Jan Gertoft, MD DMSc, jan.gerstoft@regionh.dk
- Recruiting
Bispebjerg Hospital
Copenhagen, 2400
Jesper Andreas Knudsen, MD, PhD
- Recruiting
Gentofte Hospital
Hellerup, 2900
Pernille Ravn, MD PhD, pernille.ravn.02@regionh.dk
- Recruiting
Herlev Hospital
Herlev, 2730
Suzanne Lunding, MD PhD, suzanne.lunding.01@regionh.dk
- Not yet recruiting
Herning Hospital
Herning, 7400
Rajesh Mohey, MD PhD
rajemohe@rm.dk
- Recruiting
Nordsjaellands Hospital
Hillerød, 3400
Birgitte Lindegaard Madsen, MD PhD, birgitte.lindegaard.madsen@regionh.dk
- Recruiting
Hvidovre Hospital
Hvidovre, 2650
Sandra Tingsgård, MD, +4520544094, sandra.tingsgaard@regionh.dk
- Not yet recruiting
Kolding Hospital
Kolding, 6000
Janne Jensen, MD, janne.jensen@rsyd.dk
- Not yet recruiting
Odense University Hospital
Odense, 5000
Isik Johansen, MD DMSc, isik.somuncu.johansen@rsyd.dk
- Not yet recruiting
Roskilde Hospital
Roskilde, 4000
Lothar Wiese, MD PhD, low@regionsjaelland.dk
- Not yet recruiting
Regionshospitalet Silkeborg
Silkeborg, 8600
Britta Tarp, MD PhD, brittarp@rm.dk
About this study
Official title: Short Course Antibiotic Treatment of Gram-negative Bacteremia: A Multicenter, Randomized, Non-blinded, Non-inferiority Interventional Study
GNB5 is an investigator-initiated multicentre non-inferiority randomized controlled trial which aims to assess the efficacy and safety of shortened antibiotic for patients hospitalized with a Gram negative bacteremia with a urinary tract source of infection (GNB).
Five days after initiation of antimicrobial therapy for GNB, participants are randomized 1:1 to parallel treatment arms: 5 days (intervention) or minimum 7 days (control) of antibiotic treatment. The intervention group discontinues antibiotics at day 5 if clinically stable and afebrile. The control group receives antibiotics for a duration of 7 days or longer at the discretion of the treating physician.
The primary outcome is 90-day survival without clinical or microbiological failure to treatment, which will be tested with a non inferiority margin of 10%.
Read the detailed description
Introduction: Prolonged use of antibiotics is closely related to antibiotic-associated infections, anti-microbial resistance and adverse drug events. The optimal duration of antibiotic treatment for Gram-negative bacteremia (GNB) with a urinary tract source of infection is poorly defined.
Methods and analysis: Investigator initiated multicenter, non-blinded, non-inferiority randomized controlled trial with two parallel treatment arms. One arm will receive shortened antibiotic treatment of 5 days and the other arm will receive standard antibiotic treatment of 7 days or longer. Randomization will occur in equal proportion (1:1) no later than day 5 of efficacious antibiotic treatment as determined by antibiogram. Immunosuppressed patients and those with GNB due to non-fermenting bacilli (Acinetobacter spp, Pseudomonas spp), Brucella spp, Fusobacterium spp or polymicrobial growth are ineligible.
Primary endpoint is 90-day survival without clinical or microbiological failure to treatment. Secondary endpoints include all-cause mortality, total duration of antibiotic treatment, hospital re-admission and Clostridioides difficile infection. Interim safety analysis will be performed after the recruitment of every 100 patients. Given an event rate of 12%, a margin of 10% and 90% power, the required sample size to determine non-inferiority is 380 patients. Analyses will be performed on both intention-to-treat and per-protocol populations.
Ethics and dissemination: Approval by Ethics Committee and National Competent Authorities will be obtained before initiation of the trial. Results of the main trial and each of the secondary endpoints will be submitted for publication in a peer-reviewed journal.
Impact: Demonstration of non-inferiority will provide needed evidence to safely shorten antibiotic treatment duration in GNB with a urinary tract source of infection and thereby reduce the risk of adverse events and development of resistance associated with use of antibiotics
- Being tested
- Shortened antibiotic treatment, Standard antibiotic treatment
- Keywords
- Gram-negative bacteremia, Urinary tract infection, Shortened antibiotic treatment, Bacterial infection
- Medical subject headings
- Urinary Tract Infections, Bacterial Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Shortened antibiotic treatmentOther
Shortened antibiotic treatment of 5 days. Participation in the study will only affect treatment duration and will have no influence on the choice of treatment in respect to type and dose of antibiotic treatment.
Standard antibiotic treatmentOther
Standard antibiotic treatment of minimum 7 days at the discretion of treating physician. Participation in the study will only affect treatment duration and will have no influence on the choice of treatment in respect to type and dose of antibiotic treatment.
| Study group | Role | What they receive |
|---|---|---|
| Intervention group | Experimental | Shortened antibiotic treatment of 5 days Receives: Other: Shortened antibiotic treatment |
| Control group | Active comparator | Standard antibiotic treatment of minimum 7 days at the discretion of treating physician Receives: Other: Standard antibiotic treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
90-day survival without clinical or microbiological failure to treatment
90-day survival without clinical or microbiological failure to treatment as defined:
- All-cause mortality from day of randomization and until day 90
- Microbiological failure: Recurrent bacteremia due to the same microorganism as verified by sequence analysis occurring from day of randomization and until day 90
- Clinical failure: Re-initiation of therapy against Gram-negative bacteremia for more than 48 hours due to clinical worsening suspected to be due to the initial infecting organism and for which there is no alternate diagnosis/pathogen suspected from the day of randomization and until day 90
- Distant complications of initial infection, defined by growth of the same bacteria as in the initial bacteremia (e.g. endocarditis, meningitis)
- Local suppurative complication that was not present at infection onset (e.g. renal abscess in pyelonephritis)
Measured: 90 days
Secondary outcomes (12)
Mortality
Number of deaths by any cause
Measured: 14, 30 and 90 days
Total duration of antibiotic treatment
Days that the participant receives antibiotic treatment for Gram-negative bacteremia, adding intravenous and oral therapy
Measured: 90 days
Type of antibiotic treatment
Antibiotic treatment for Gram-negative bacteremia given by antibiogram
Measured: 90 days
Duration of antibiotic treatment
Duration of antibiotic treatment for Gram-negative bacteremia given by antibiogram
Measured: 90 days
Total length of hospital stay
Days from the date of hospital admission for Gram-negative bacteremia to the date of discharge
Measured: 90 days
Hospital re-admission
Number of participants with readmissions for reasons related to or unrelated to Gram-negative bacteremia
Measured: 30 and 90 days
Antibiotic adverse events
Number of participants with adverse events with possible relation to the antibiotic treatment of Gram-negative bacteremia
Measured: 90 days
Use of antimicrobials after discharge
Days of antibiotic treatment for any reason after hospital discharge
Measured: 90 days
Severe adverse events
Number of participants with serious adverse events according to International Council of Harmonisation-Good Clinical Practice (ICH-GCP) guidelines
Measured: 90 days
Acute kidney injury
Number of participants with acute kidney injury is defined according to RIFLE criteria as increased creatinine level x 1.5 from baseline or estimated glomerular filtration rate (eGFR) decrease >25% or urine output of <0.5 ml/kg/h for 6 hours.
Measured: 90 days
Clostridioides difficile infection
Number of participants with Clostridioides difficile infection
Measured: 90 days
Multidrug-resistance organism
Multidrug-resistance organism defined as identification of resistant bacteria in a clinical specimen obtained only from a clinical infection.
Measured: 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Mar 2020
- Study start11 Mar 2020
- Primary completion1 Oct 2026 (estimated)
- Study completion1 Oct 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (26)Papers the sponsor has linked to this study.
- Other trials for Gram-negative BacteremiaStudies 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
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 380 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Thomas Benfield
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Thomas Benfield, Hvidovre University Hospital
- Investigators
- Sandra Tingsgård, MD, Principal investigator, Hvidovre University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04291768
- Sponsor's protocol ID
- 190801
- Other IDs
- 2019-003282-17, H-19085920, 2019
- Acronym
- GNB5
- Status last verified
- Feb 2023
- First submitted
- 24 Feb 2020
- Last updated
- 8 Feb 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Demographics, medical history, and laboratory data will be preserved to validate and replicate described research. Study protocol and statistical analysis plan will be publicly available. Data will be collected in the electronic data capture system (REDCap) and analyzed using open-source statistical packages in R. Data will be available immediately following the publication of the primary outcome. Data will be preserved for 10 upon study start. Anonymized trial data will be made available through relevant public databases when the trial ends. On request, anonymized patient-level data, the statistical code, and other relevant supporting information will be made available by contact with the corresponding author. Study data will be published only in pseudonymous form. Compliance with the plan will be monitored by the primary investigator routinely.
Publications
Kang CI, Kim SH, Park WB, Lee KD, Kim HB, Kim EC, Oh MD, Choe KW. Bloodstream infections caused by antibiotic-resistant gram-negative bacilli: risk factors for mortality and impact of inappropriate initial antimicrobial therapy on outcome. Antimicrob Agents Chemother. 2005 Feb;49(2):760-6. doi: 10.1128/AAC.49.2.760-766.2005.
PubMed 15673761Biedenbach DJ, Moet GJ, Jones RN. Occurrence and antimicrobial resistance pattern comparisons among bloodstream infection isolates from the SENTRY Antimicrobial Surveillance Program (1997-2002). Diagn Microbiol Infect Dis. 2004 Sep;50(1):59-69. doi: 10.1016/j.diagmicrobio.2004.05.003.
PubMed 15380279de Kraker ME, Jarlier V, Monen JC, Heuer OE, van de Sande N, Grundmann H. The changing epidemiology of bacteraemias in Europe: trends from the European Antimicrobial Resistance Surveillance System. Clin Microbiol Infect. 2013 Sep;19(9):860-8. doi: 10.1111/1469-0691.12028. Epub 2012 Oct 8.
PubMed 23039210Sogaard M, Norgaard M, Dethlefsen C, Schonheyder HC. Temporal changes in the incidence and 30-day mortality associated with bacteremia in hospitalized patients from 1992 through 2006: a population-based cohort study. Clin Infect Dis. 2011 Jan 1;52(1):61-9. doi: 10.1093/cid/ciq069.
PubMed 21148521DANMAP 2017 - Use of antimicrobial agents and occurrence of antimicrobial resistance in bacteria from food animals, food and humans in Denmark. 2017
Goossens H, Ferech M, Vander Stichele R, Elseviers M; ESAC Project Group. Outpatient antibiotic use in Europe and association with resistance: a cross-national database study. Lancet. 2005 Feb 12-18;365(9459):579-87. doi: 10.1016/S0140-6736(05)17907-0.
PubMed 15708101Lessa FC, Mu Y, Bamberg WM, Beldavs ZG, Dumyati GK, Dunn JR, Farley MM, Holzbauer SM, Meek JI, Phipps EC, Wilson LE, Winston LG, Cohen JA, Limbago BM, Fridkin SK, Gerding DN, McDonald LC. Burden of Clostridium difficile infection in the United States. N Engl J Med. 2015 Feb 26;372(9):825-34. doi: 10.1056/NEJMoa1408913.
PubMed 25714160Cunha BA. Antibiotic side effects. Med Clin North Am. 2001 Jan;85(1):149-85. doi: 10.1016/s0025-7125(05)70309-6.
PubMed 11190350Tamma PD, Avdic E, Li DX, Dzintars K, Cosgrove SE. Association of Adverse Events With Antibiotic Use in Hospitalized Patients. JAMA Intern Med. 2017 Sep 1;177(9):1308-1315. doi: 10.1001/jamainternmed.2017.1938.
PubMed 28604925Branch-Elliman W, O'Brien W, Strymish J, Itani K, Wyatt C, Gupta K. Association of Duration and Type of Surgical Prophylaxis With Antimicrobial-Associated Adverse Events. JAMA Surg. 2019 Jul 1;154(7):590-598. doi: 10.1001/jamasurg.2019.0569.
PubMed 31017647Pollack LA, Srinivasan A. Core elements of hospital antibiotic stewardship programs from the Centers for Disease Control and Prevention. Clin Infect Dis. 2014 Oct 15;59 Suppl 3(Suppl 3):S97-100. doi: 10.1093/cid/ciu542.
PubMed 25261548Rice LB. The Maxwell Finland Lecture: for the duration-rational antibiotic administration in an era of antimicrobial resistance and clostridium difficile. Clin Infect Dis. 2008 Feb 15;46(4):491-6. doi: 10.1086/526535.
PubMed 18194098Gupta K, Hooton TM, Naber KG, Wullt B, Colgan R, Miller LG, Moran GJ, Nicolle LE, Raz R, Schaeffer AJ, Soper DE; Infectious Diseases Society of America; European Society for Microbiology and Infectious Diseases. International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: A 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clin Infect Dis. 2011 Mar 1;52(5):e103-20. doi: 10.1093/cid/ciq257.
PubMed 21292654Corona A, Bertolini G, Ricotta AM, Wilson A, Singer M. Variability of treatment duration for bacteraemia in the critically ill: a multinational survey. J Antimicrob Chemother. 2003 Nov;52(5):849-52. doi: 10.1093/jac/dkg447. Epub 2003 Sep 30.
PubMed 14519681Chotiprasitsakul D, Han JH, Cosgrove SE, Harris AD, Lautenbach E, Conley AT, Tolomeo P, Wise J, Tamma PD; Antibacterial Resistance Leadership Group. Comparing the Outcomes of Adults With Enterobacteriaceae Bacteremia Receiving Short-Course Versus Prolonged-Course Antibiotic Therapy in a Multicenter, Propensity Score-Matched Cohort. Clin Infect Dis. 2018 Jan 6;66(2):172-177. doi: 10.1093/cid/cix767.
PubMed 29190320
Study at a glance
From the registry record, last updated by the sponsor on 8 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Short Course Antibiotic Treatment of Gram-negative Bacteremia: A Multicenter, Randomized, Non-blinded, Non-inferiority Interventional Study
- ClinicalTrials.gov ID
- NCT04291768
- Acronym / sponsor ID
- GNB5 / 190801
- Keywords
- Gram-negative bacteremia, Urinary tract infection, Shortened antibiotic treatment, Bacterial infection
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 380 participants (estimated)
- Lead sponsor
- Thomas BenfieldUniversity, hospital or other
- Study start
- 11 Mar 2020 (actual)
- Primary completion
- 1 Oct 2026 (estimated)
- Study completion
- 1 Oct 2026 (estimated)
- First posted
- 2 Mar 2020 (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.
GNB5 is an investigator-initiated multicentre non-inferiority randomized controlled trial which aims to assess the efficacy and safety of shortened antibiotic for patients hospitalized with a Gram negative bacteremia with a urinary tract source of infection (GNB).
Five days after initiation of antimicrobial therapy for GNB, participants are randomized 1:1 to parallel treatment arms: 5 days (intervention) or minimum 7 days (control) of antibiotic treatment. The intervention group discontinues antibiotics at day 5 if clinically stable and afebrile. The control group receives antibiotics for a duration of 7 days or longer at the discretion of the treating physician.
The primary outcome is 90-day survival without clinical or microbiological failure to treatment, which will be tested with a non inferiority margin of 10%.
Detailed description
Introduction: Prolonged use of antibiotics is closely related to antibiotic-associated infections, anti-microbial resistance and adverse drug events. The optimal duration of antibiotic treatment for Gram-negative bacteremia (GNB) with a urinary tract source of infection is poorly defined.
Methods and analysis: Investigator initiated multicenter, non-blinded, non-inferiority randomized controlled trial with two parallel treatment arms. One arm will receive shortened antibiotic treatment of 5 days and the other arm will receive standard antibiotic treatment of 7 days or longer. Randomization will occur in equal proportion (1:1) no later than day 5 of efficacious antibiotic treatment as determined by antibiogram. Immunosuppressed patients and those with GNB due to non-fermenting bacilli (Acinetobacter spp, Pseudomonas spp), Brucella spp, Fusobacterium spp or polymicrobial growth are ineligible.
Primary endpoint is 90-day survival without clinical or microbiological failure to treatment. Secondary endpoints include all-cause mortality, total duration of antibiotic treatment, hospital re-admission and Clostridioides difficile infection. Interim safety analysis will be performed after the recruitment of every 100 patients. Given an event rate of 12%, a margin of 10% and 90% power, the required sample size to determine non-inferiority is 380 patients. Analyses will be performed on both intention-to-treat and per-protocol populations.
Ethics and dissemination: Approval by Ethics Committee and National Competent Authorities will be obtained before initiation of the trial. Results of the main trial and each of the secondary endpoints will be submitted for publication in a peer-reviewed journal.
Impact: Demonstration of non-inferiority will provide needed evidence to safely shorten antibiotic treatment duration in GNB with a urinary tract source of infection and thereby reduce the risk of adverse events and development of resistance associated with use of antibiotics
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intervention group | Experimental | Other: Shortened antibiotic treatmentShortened antibiotic treatment of 5 days |
| Control group | Active comparator | Other: Standard antibiotic treatmentStandard antibiotic treatment of minimum 7 days at the discretion of treating physician |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Age >18 years
- Blood culture positive for Gram-negative bacteria
- Evidence of urinary tract source of infection (positive urine culture or at least one clinical symptom compatible with urinary tract infection)
- Antibiotic treatment with antimicrobial activity to Gram-negative bacteria administrated within 12 hours of first blood culture
- Temperature <37.8°C at randomization
Key exclusion criteria (7 listed)
- Antibiotic treatment (>2 day) with antimicrobial activity to Gram-negative bacteria within 14 days of inclusion
- Gram-negative bacteremia within 30 days of blood culture
- Immunosuppression (Untreated HIV-infection, Neutropenia (absolute neutrophil count < 1.0 x 109/l), Untreated terminal cancer, Receiving immunosuppressive agents (ATC-code L04A), Corticosteroid treatment (≥20 mg/day prednisone or the equivalent for >14 days) within the last 30 days, Chemotherapy within the last 30 days, Immunosuppressed after solid organ transplantation, Asplenia)
- Polymicrobial growth in blood culture
- Bacteremia with non-fermenting Gram-negative bacteria (Acinetobacter spp, Burkholderia spp, Pseudomonas spp), Brucella spp, or Fusobacterium spp
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Shortened antibiotic treatmentShortened antibiotic treatment of 5 days. Participation in the study will only affect treatment duration and will have no influence on the choice of treatment in respect to type and dose of antibiotic treatment. | Other | Intervention group |
| Standard antibiotic treatmentStandard antibiotic treatment of minimum 7 days at the discretion of treating physician. Participation in the study will only affect treatment duration and will have no influence on the choice of treatment in respect to type and dose of antibiotic treatment. | Other | Control group |
Primary outcome
90-day survival without clinical or microbiological failure to treatment
Time frame: 90 days
90-day survival without clinical or microbiological failure to treatment as defined: 1. All-cause mortality from day of randomization and until day 90 2. Microbiological failure: Recurrent bacteremia due to the same microorganism as verified by sequence analysis occurring from day of randomization and until day 90 3. Clinical failure: Re-initiation of therapy against Gram-negative bacteremia for more than 48 hours due to clinical worsening suspected to be due to the initial infecting organism and for which there is no alternate diagnosis/pathogen suspected from the day of randomization and until day 90 1. Distant complications of initial infection, defined by growth of the same bacteria as in the initial bacteremia (e.g. endocarditis, meningitis) 2. Local suppurative complication that was not present at infection onset (e.g. renal abscess in pyelonephritis)
12 secondary outcomes
Mortality
Time frame: 14, 30 and 90 days
Total duration of antibiotic treatment
Time frame: 90 days
Type of antibiotic treatment
Time frame: 90 days
Duration of antibiotic treatment
Time frame: 90 days
Total length of hospital stay
Time frame: 90 days
Hospital re-admission
Time frame: 30 and 90 days
Antibiotic adverse events
Time frame: 90 days
Use of antimicrobials after discharge
Time frame: 90 days
Severe adverse events
Time frame: 90 days
Acute kidney injury
Time frame: 90 days
Clostridioides difficile infection
Time frame: 90 days
Multidrug-resistance organism
Time frame: 90 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Feb 2023.
- Background: PubMed 15673761Kang CI, Kim SH, Park WB, Lee KD, Kim HB, Kim EC, Oh MD, Choe KW. Bloodstream infections caused by antibiotic-resistant gram-negative bacilli: risk factors for mortality and impact of inappropriate initial antimicrobial therapy on outcome. Antimicrob Agents Chemother. 2005 Feb;49(2):760-6. doi: 10.1128/AAC.49.2.760-766.2005.
- Background: PubMed 15380279Biedenbach DJ, Moet GJ, Jones RN. Occurrence and antimicrobial resistance pattern comparisons among bloodstream infection isolates from the SENTRY Antimicrobial Surveillance Program (1997-2002). Diagn Microbiol Infect Dis. 2004 Sep;50(1):59-69. doi: 10.1016/j.diagmicrobio.2004.05.003.
- Background: PubMed 23039210de Kraker ME, Jarlier V, Monen JC, Heuer OE, van de Sande N, Grundmann H. The changing epidemiology of bacteraemias in Europe: trends from the European Antimicrobial Resistance Surveillance System. Clin Microbiol Infect. 2013 Sep;19(9):860-8. doi: 10.1111/1469-0691.12028. Epub 2012 Oct 8.
- Background: PubMed 21148521Sogaard M, Norgaard M, Dethlefsen C, Schonheyder HC. Temporal changes in the incidence and 30-day mortality associated with bacteremia in hospitalized patients from 1992 through 2006: a population-based cohort study. Clin Infect Dis. 2011 Jan 1;52(1):61-9. doi: 10.1093/cid/ciq069.
- BackgroundDANMAP 2017 - Use of antimicrobial agents and occurrence of antimicrobial resistance in bacteria from food animals, food and humans in Denmark. 2017
- Background: PubMed 15708101Goossens H, Ferech M, Vander Stichele R, Elseviers M; ESAC Project Group. Outpatient antibiotic use in Europe and association with resistance: a cross-national database study. Lancet. 2005 Feb 12-18;365(9459):579-87. doi: 10.1016/S0140-6736(05)17907-0.
- Background: PubMed 25714160Lessa FC, Mu Y, Bamberg WM, Beldavs ZG, Dumyati GK, Dunn JR, Farley MM, Holzbauer SM, Meek JI, Phipps EC, Wilson LE, Winston LG, Cohen JA, Limbago BM, Fridkin SK, Gerding DN, McDonald LC. Burden of Clostridium difficile infection in the United States. N Engl J Med. 2015 Feb 26;372(9):825-34. doi: 10.1056/NEJMoa1408913.
- Background: PubMed 11190350Cunha BA. Antibiotic side effects. Med Clin North Am. 2001 Jan;85(1):149-85. doi: 10.1016/s0025-7125(05)70309-6.
- Background: PubMed 28604925Tamma PD, Avdic E, Li DX, Dzintars K, Cosgrove SE. Association of Adverse Events With Antibiotic Use in Hospitalized Patients. JAMA Intern Med. 2017 Sep 1;177(9):1308-1315. doi: 10.1001/jamainternmed.2017.1938.
- Background: PubMed 31017647Branch-Elliman W, O'Brien W, Strymish J, Itani K, Wyatt C, Gupta K. Association of Duration and Type of Surgical Prophylaxis With Antimicrobial-Associated Adverse Events. JAMA Surg. 2019 Jul 1;154(7):590-598. doi: 10.1001/jamasurg.2019.0569.
- Background: PubMed 25261548Pollack LA, Srinivasan A. Core elements of hospital antibiotic stewardship programs from the Centers for Disease Control and Prevention. Clin Infect Dis. 2014 Oct 15;59 Suppl 3(Suppl 3):S97-100. doi: 10.1093/cid/ciu542.
- Background: PubMed 18194098Rice LB. The Maxwell Finland Lecture: for the duration-rational antibiotic administration in an era of antimicrobial resistance and clostridium difficile. Clin Infect Dis. 2008 Feb 15;46(4):491-6. doi: 10.1086/526535.
- Individual participant dataSharing planned: Yes. Demographics, medical history, and laboratory data will be preserved to validate and replicate described research. Study protocol and statistical analysis plan will be publicly available. Data will be collected in the electronic data capture system (REDCap) and analyzed using open-source statistical packages in R. Data will be available immediately following the publication of the primary outcome. Data will be preserved for 10 upon study start. Anonymized trial data will be made available through relevant public databases when the trial ends. On request, anonymized patient-level data, the statistical code, and other relevant supporting information will be made available by contact with the corresponding author. Study data will be published only in pseudonymous form. Compliance with the plan will be monitored by the primary investigator routinely.
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The Impact of Fast Antimicrobial Sensitivity Testing Tools on Stewardship Antibiotic and Clinical Outcome (ACT-FAST)
Bloodstream Infection, Gram-Negative Infections
Recruiting
Gram-Negative Bloodstream Infection Oral Antibiotic Therapy Trial
Gram-negative Bacteremia
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.
Thomas Benfield, MD DMSc contact
Sandra Tingsgård, MD principal investigator
Hvidovre University Hospital
13 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Shortened antibiotic treatment and Standard antibiotic treatment in people with Gram-negative Bacteremia and Urinary Tract Infection Bacterial, run by Thomas Benfield at 13 sites in Denmark.
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 7 inclusion and 7 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 8 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in Denmark. 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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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 Sandra Tingsgård, MD (+4520544094, sandra.tingsgaard@regionh.dk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
90-day survival without clinical or microbiological failure to treatment (time frame: 90 days). 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 NCT04291768, which also lists 26 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 8 Feb 2023.