Shortened Antibiotic Treatment of 5 Days in Gram-negative Bacteremia

NCT04291768 | Recruiting Phase 4 DMC

• 3 other identifiers: 1908012019-003282-17H-19085920
• Study Type: interventional
• Target: 380
• Locations: 1 country
• Sites: 13

Brief 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%.

Conditions

Gram-negative Bacteremia; Urinary Tract Infection Bacterial

Keywords

Gram-negative bacteremia; Urinary tract infection; Shortened antibiotic treatment; Bacterial infection

Outcome Measures

Primary Outcomes (1)

• 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)

  90 days

Secondary Outcomes (12)

• Mortality

  14, 30 and 90 days

• Total duration of antibiotic treatment

  90 days

• Type of antibiotic treatment

  90 days

• Duration of antibiotic treatment

  90 days

• Total length of hospital stay

  90 days

Study Arms (2)

Intervention group

EXPERIMENTAL

Shortened antibiotic treatment of 5 days

Other: Shortened antibiotic treatment

Control group

ACTIVE COMPARATOR

Standard antibiotic treatment of minimum 7 days at the discretion of treating physician

Other: Standard antibiotic treatment

Interventions

Shortened antibiotic treatment OTHER

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.

Intervention group

Standard antibiotic treatment OTHER

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.

Control group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Thomas Benfield: lead

Study Sites (13)

University Hospital of Aalborg

Aalborg, 9000, Denmark

NOT YET RECRUITING

University Hospital of Aarhus

Aarhus, 8200, Denmark

NOT YET RECRUITING

Rigshospitalet

Copenhagen, 2100, Denmark

NOT YET RECRUITING

Bispebjerg Hospital

Copenhagen, 2400, Denmark

RECRUITING

Gentofte Hospital

Hellerup, 2900, Denmark

RECRUITING

Herlev Hospital

Herlev, 2730, Denmark

RECRUITING

Herning Hospital

Herning, 7400, Denmark

NOT YET RECRUITING

Nordsjaellands Hospital

Hillerød, 3400, Denmark

RECRUITING

Hvidovre Hospital

Hvidovre, 2650, Denmark

RECRUITING

Kolding Hospital

Kolding, 6000, Denmark

NOT YET RECRUITING

Odense University Hospital

Odense, 5000, Denmark

NOT YET RECRUITING

Roskilde Hospital

Roskilde, 4000, Denmark

NOT YET RECRUITING

Regionshospitalet Silkeborg

Silkeborg, 8600, Denmark

NOT YET RECRUITING

Related Publications (26)

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• DANMAP 2017 - Use of antimicrobial agents and occurrence of antimicrobial resistance in bacteria from food animals, food and humans in Denmark. 2017

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  PMID: 18194098 BACKGROUND

• Gupta 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.

  PMID: 21292654 BACKGROUND

• Corona 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.

  PMID: 14519681 BACKGROUND

• Chotiprasitsakul 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.

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• Yahav D, Franceschini E, Koppel F, Turjeman A, Babich T, Bitterman R, Neuberger A, Ghanem-Zoubi N, Santoro A, Eliakim-Raz N, Pertzov B, Steinmetz T, Stern A, Dickstein Y, Maroun E, Zayyad H, Bishara J, Alon D, Edel Y, Goldberg E, Venturelli C, Mussini C, Leibovici L, Paul M; Bacteremia Duration Study Group. Seven Versus 14 Days of Antibiotic Therapy for Uncomplicated Gram-negative Bacteremia: A Noninferiority Randomized Controlled Trial. Clin Infect Dis. 2019 Sep 13;69(7):1091-1098. doi: 10.1093/cid/ciy1054.

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• Huttner A, Albrich WC, Bochud PY, Gayet-Ageron A, Rossel A, Dach EV, Harbarth S, Kaiser L. PIRATE project: point-of-care, informatics-based randomised controlled trial for decreasing overuse of antibiotic therapy in Gram-negative bacteraemia. BMJ Open. 2017 Jul 13;7(7):e017996. doi: 10.1136/bmjopen-2017-017996.

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• Tingsgard S, Israelsen SB, Thorlacius-Ussing L, Frahm Kirk K, Lindegaard B, Johansen IS, Knudsen A, Lunding S, Ravn P, Ostergaard Andersen C, Benfield T. Short course antibiotic treatment of Gram-negative bacteraemia (GNB5): a study protocol for a randomised controlled trial. BMJ Open. 2023 May 8;13(5):e068606. doi: 10.1136/bmjopen-2022-068606.

  PMID: 37156588 DERIVED

MeSH Terms

Conditions

Urinary Tract Infections; Bacterial Infections

Condition Hierarchy (Ancestors)

Infections; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Bacterial Infections and Mycoses

Study Officials

• Sandra Tingsgård, MD

  Hvidovre University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sandra Tingsgård, MD

CONTACT

+4520544094; sandra.tingsgaard@regionh.dk

Thomas Benfield, MD DMSc

CONTACT

thomas.lars.benfield@regionh.dk

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical Professor

Study Record Dates

• First Submitted: February 24, 2020
• First Posted: March 2, 2020
• Study Start: March 11, 2020
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: February 8, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• 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.

Locations

DK (13)