A Phase 4 interventional study of Shortened antibiotic treatment and Standard antibiotic treatment in Gram-negative Bacteremia and Urinary Tract Infection Bacterial, sponsored by Thomas Benfield. Recruiting at 13 sites in Denmark. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-02-08.
Sponsored by Thomas Benfield · Phase 4, Interventional, and Treatment
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%.
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
803 studies on the registry are indexed under Urinary Tract Infections; 133 are open to participants now.
This study's planned enrollment of 380 is above the median of 131 across 560 interventional studies indexed under Urinary Tract Infections.
Browse Urinary Tract Infections studies →Thomas Benfield is the lead sponsor of 7 studies on the registry; 2 are open to participants now.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Absolute neutrophil count (ANC)
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Shortened antibiotic treatment of 5 days
Other: Shortened antibiotic treatment
Standard antibiotic treatment of minimum 7 days at the discretion of treating physician
Other: Standard 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.
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
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)
Time frame: 90 days
Mortality
Number of deaths by any cause
Time frame: 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
Time frame: 90 days
Type of antibiotic treatment
Antibiotic treatment for Gram-negative bacteremia given by antibiogram
Time frame: 90 days
Duration of antibiotic treatment
Duration of antibiotic treatment for Gram-negative bacteremia given by antibiogram
Time frame: 90 days
Total length of hospital stay
Days from the date of hospital admission for Gram-negative bacteremia to the date of discharge
Time frame: 90 days
Hospital re-admission
Number of participants with readmissions for reasons related to or unrelated to Gram-negative bacteremia
Time frame: 30 and 90 days
Antibiotic adverse events
Number of participants with adverse events with possible relation to the antibiotic treatment of Gram-negative bacteremia
Time frame: 90 days
Use of antimicrobials after discharge
Days of antibiotic treatment for any reason after hospital discharge
Time frame: 90 days
Severe adverse events
Number of participants with serious adverse events according to International Council of Harmonisation-Good Clinical Practice (ICH-GCP) guidelines
Time frame: 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.
Time frame: 90 days
Clostridioides difficile infection
Number of participants with Clostridioides difficile infection
Time frame: 90 days
Multidrug-resistance organism
Multidrug-resistance organism defined as identification of resistant bacteria in a clinical specimen obtained only from a clinical infection.
Time frame: 90 days
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: 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.
Supporting information: Study protocol, Statistical analysis plan, Informed consent form
Time frame: Data will be available immediately following the publication of the primary outcome. Data will be preserved for 10 upon study start.
Access criteria: On request, anonymized patient-level data, the statistical code, and other relevant supporting information will be made available by contact with the corresponding author.
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Thomas Benfield