Shortened Antibiotic Treatment of 5 Days in Gram-negative Bacteremia (GNB5)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT04291768|
Recruitment Status : Recruiting
First Posted : March 2, 2020
Last Update Posted : November 19, 2020
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%.
|Condition or disease||Intervention/treatment||Phase|
|Gram-negative Bacteremia Urinary Tract Infection Bacterial||Other: Shortened antibiotic treatment Other: Standard antibiotic treatment||Phase 4|
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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||380 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Short Course Antibiotic Treatment of Gram-negative Bacteremia: A Multicenter, Randomized, Non-blinded, Non-inferiority Interventional Study|
|Actual Study Start Date :||March 11, 2020|
|Estimated Primary Completion Date :||October 1, 2023|
|Estimated Study Completion Date :||October 1, 2023|
Experimental: Intervention group
Shortened antibiotic treatment of 5 days
Other: Shortened antibiotic treatment
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.
Active Comparator: Control group
Standard antibiotic treatment of minimum 7 days at the discretion of treating physician
Other: Standard antibiotic treatment
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.
- 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:
- 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)
- Mortality [ Time Frame: 14, 30 and 90 days ]Number of deaths by any cause
- Total duration of antibiotic treatment [ Time Frame: 90 days ]Days that the participant receives antibiotic treatment for Gram-negative bacteremia, adding intravenous and oral therapy
- Type of antibiotic treatment [ Time Frame: 90 days ]Antibiotic treatment for Gram-negative bacteremia given by antibiogram
- Duration of antibiotic treatment [ Time Frame: 90 days ]Duration of antibiotic treatment for Gram-negative bacteremia given by antibiogram
- Total length of hospital stay [ Time Frame: 90 days ]Days from the date of hospital admission for Gram-negative bacteremia to the date of discharge
- Hospital re-admission [ Time Frame: 30 and 90 days ]Number of participants with readmissions for reasons related to or unrelated to Gram-negative bacteremia
- Antibiotic adverse events [ Time Frame: 90 days ]Number of participants with adverse events with possible relation to the antibiotic treatment of Gram-negative bacteremia
- Use of antimicrobials after discharge [ Time Frame: 90 days ]Days of antibiotic treatment for any reason after hospital discharge
- Severe adverse events [ Time Frame: 90 days ]Number of participants with serious adverse events according to International Council of Harmonisation-Good Clinical Practice (ICH-GCP) guidelines
- Acute kidney injury [ Time Frame: 90 days ]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.
- Clostridioides difficile infection [ Time Frame: 90 days ]Number of participants with Clostridioides difficile infection
- Multidrug-resistance organism [ Time Frame: 90 days ]Multidrug-resistance organism defined as identification of resistant bacteria in a clinical specimen obtained only from a clinical infection.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04291768
|Contact: Sandra Tingsgård, MDfirstname.lastname@example.org|
|Contact: Thomas Benfield, MD DMScemail@example.com|
|University Hospital of Aalborg||Not yet recruiting|
|Aalborg, Denmark, 9000|
|Contact: Henrik Nielsen, MD DMSc firstname.lastname@example.org|
|Rigshospitalet||Not yet recruiting|
|Copenhagen, Denmark, 2100|
|Contact: Jan Gertoft, MD DMSc email@example.com|
|Hellerup, Denmark, 2900|
|Contact: Pernille Ravn, MD PhD firstname.lastname@example.org|
|Herlev, Denmark, 2730|
|Contact: Suzanne Lunding, MD PhD email@example.com|
|Herning Hospital||Not yet recruiting|
|Herning, Denmark, 7400|
|Contact: Rajesh Mohey, MD PhD|
|Hillerød, Denmark, 3400|
|Contact: Birgitte Lindegaard Madsen, MD PhD firstname.lastname@example.org|
|Hvidovre, Denmark, 2650|
|Contact: Sandra Tingsgård, MD +4520544094 email@example.com|
|Kolding Hospital||Not yet recruiting|
|Kolding, Denmark, 6000|
|Contact: Janne Jensen, MD firstname.lastname@example.org|
|Odense University Hospital||Not yet recruiting|
|Odense, Denmark, 5000|
|Contact: Isik Johansen, MD DMSc email@example.com|
|Roskilde Hospital||Not yet recruiting|
|Roskilde, Denmark, 4000|
|Contact: Lothar Wiese, MD PhD firstname.lastname@example.org|
|Regionshospitalet Silkeborg||Not yet recruiting|
|Silkeborg, Denmark, 8600|
|Contact: Britta Tarp, MD PhD email@example.com|
|University Hospital of Aarhus||Not yet recruiting|
|Århus, Denmark, 8200|
|Contact: Lars Østergaard, MD DMSc firstname.lastname@example.org|
|Principal Investigator:||Sandra Tingsgård, MD||Hvidovre University Hospital|