Shortened Antibiotic Treatment of 5 Days in Gram-negative Bacteremia

  • STATUS
    Recruiting
  • End date
    Oct 1, 2023
  • participants needed
    380
  • sponsor
    Thomas Benfield
Updated on 26 January 2021

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).

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%.

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

Details
Condition Gram Negative Bacteremia, Urinary Tract Infection Bacterial
Treatment Standard Antibiotic Treatment, Shortened antibiotic treatment
Clinical Study IdentifierNCT04291768
SponsorThomas Benfield
Last Modified on26 January 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

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 <37.8C 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

Exclusion Criteria

Antibiotic treatment (>1 day) with antimicrobial activity to Gram-negative bacteria within 14 days of inclusion
Polymicrobial growth in blood culture
Gram-negative bacteremia within 30 days of blood culture
Bacteremia with non-fermenting Gram-negative bacteria (Acinetobacter spp, Burkholderia spp, Pseudomonas spp), Brucella spp, or Fusobacterium spp
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)
Failure to remove source of infection within 72 hours of first blood culture (e.g. change of catheter demeure)
Pregnancy or breastfeeding
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