NCT03101072

Brief Summary

Gram-negative bacteremia (GNB) is a frequent hospital \& community-acquired infection, yet there is as yet no evidence from randomized studies on the optimal duration of antibiotic therapy. This point-of-care, multicenter randomized controlled non-inferiority trial will randomize 500 patients with GNB on day 5 of appropriate antibiotic therapy to either (1) a total of 7 days of antibiotic therapy, (2) a total of 14 days of antibiotic therapy, or (3) an individualized duration of antibiotic therapy (guided by the patient's clinical course \& C-reactive protein levels). The primary outcome is the incidence of clinical failure at day 30.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
504

participants targeted

Target at P75+ for not_applicable

Timeline
Completed

Started Apr 2017

Typical duration for not_applicable

Geographic Reach
1 country

3 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 29, 2017

Completed
6 days until next milestone

First Posted

Study publicly available on registry

April 4, 2017

Completed
23 days until next milestone

Study Start

First participant enrolled

April 27, 2017

Completed
2.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 11, 2019

Completed
3 months until next milestone

Study Completion

Last participant's last visit for all outcomes

August 26, 2019

Completed
Last Updated

November 19, 2019

Status Verified

November 1, 2019

Enrollment Period

2.1 years

First QC Date

March 29, 2017

Last Update Submit

November 18, 2019

Conditions

Bacteraemia Caused by Gram-Negative Bacteria

Keywords

Gram-negative bacteremiaantibiotic durationspoint-of-care randomization

Outcome Measures

Primary Outcomes (1)

  • Incidence of clinical failure in all arms

    Clinical failure is defined by the presence of at least one of the following: * Relapse: a recurrent bacteremia due to the same bacterium occurring from the day of treatment cessation and until day 30 * Local suppurative complication that was not present/apparent at infection onset (e.g., renal abscess in pyelonephritis, empyema in pneumonia) * Distant complications of the initial infection, defined by growth of the same bacterium causing the initial bacteremia (as determined by antibiotic susceptibility profiling) * The restarting of Gram-negative-directed antibiotic therapy after its initial discontinuation due to clinical worsening suspected to be due to the initial infecting organism and for which there is no alternate diagnosis/pathogen suspected * Death due to any cause through day 30

    day 30 (with day 1 being the first day of microbiologically efficacious antibiotic therapy)

Secondary Outcomes (5)

  • Incidence of clinical failure in all arms

    day 60

  • Incidence of clinical failure in all arms

    day 90

  • Incidence of all-cause mortality in all arms

    day 90

  • Incidence of Clostridium difficile infection in all arms

    day 90

  • Incidence of emergence of resistance to the study antibiotic in all arms

    day 90

Study Arms (3)

"Fixed long" antibiotic course

ACTIVE COMPARATOR

Patients randomized to this group will receive a "fixed long" antibiotic course of 14 days.

Other: "Fixed long" antibiotic course of 14 days

"Fixed short" antibiotic course

EXPERIMENTAL

Patients randomized to this group will receive a "fixed short" antibiotic course of 7 days.

Other: "Fixed short" antibiotic course of 7 days

"Individualized" antibiotic course

EXPERIMENTAL

"Individualized" antibiotic course: starting on day 5, therapy will be discontinued after the patient has been afebrile for 48 hours and the CRP level has decreased from its peak by at least 75%

Other: "Individualized duration" of antibiotic therapy

Interventions

"Fixed long" antibiotic course of 14 daysOTHER

Only the duration of antibiotic therapy will be investigated in this study. (In all arms, the choice and mode of administration (IV vs. PO) of antibiotic(s) will be left to the patient's attending physician and consulting infectious disease specialist and thus will follow usual standards of care.)

"Fixed long" antibiotic course
"Fixed short" antibiotic course of 7 daysOTHER

Only the duration of antibiotic therapy will be investigated in this study. (In all arms, the choice and mode of administration (IV vs. PO) of antibiotic(s) will be left to the patient's attending physician and consulting infectious disease specialist and thus will follow usual standards of care.)

"Fixed short" antibiotic course
"Individualized duration" of antibiotic therapyOTHER

Only the duration of antibiotic therapy will be investigated in this study. (In all arms, the choice and mode of administration (IV vs. PO) of antibiotic(s) will be left to the patient's attending physician and consulting infectious disease specialist and thus will follow usual standards of care.)

"Individualized" antibiotic course

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Age ≥ 18 years
  • Presence of Gram-negative bacteria in at least one blood culture bottle
  • Treatment with a microbiologically efficacious antibiotic

You may not qualify if:

  • Immunosuppression (including HIV infection with CD4 cell count ≤500/µl, hematopoietic stem-cell transplantation in the first month after transplantation and at any time before engraftment, neutropenia in the 48 hours prior to randomization, receipt of high-dose steroids \[\>40 mg prednisone or its equivalent\] daily for \> 2 weeks) in the two weeks prior to randomization
  • GNB due to the following complicated infections:
  • Endocarditis or other endovascular infection without a removable focus
  • Necrotizing fasciitis
  • Osteomyelitis or septic arthritis
  • Confirmed prostatitis
  • Undrainable abscess or other unresolved sources requiring surgical intervention (e.g., cholecystitis) at the time of enrollment
  • Central nervous system infections
  • Empyema
  • GNB due to non-fermenting bacilli (Acinetobacter spp., Burkholderia spp., Pseudomonas spp.), Brucella spp., Fusobacterium spp., or polymicrobial growth with Gram-positive organisms
  • Fever (≥38º C) or hemodynamic instability in the 24h prior to recruitment

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

Cantonal Hospital St Gallen

Sankt Gallen, Canton of St. Gallen, Switzerland

Location

Lausanne University Hospital

Lausanne, Canton of Vaud, Switzerland

Location

Geneva University Hospitals

Geneva, 1205, Switzerland

Location

Related Publications (2)

  • von Dach E, Albrich WC, Brunel AS, Prendki V, Cuvelier C, Flury D, Gayet-Ageron A, Huttner B, Kohler P, Lemmenmeier E, McCallin S, Rossel A, Harbarth S, Kaiser L, Bochud PY, Huttner A. Effect of C-Reactive Protein-Guided Antibiotic Treatment Duration, 7-Day Treatment, or 14-Day Treatment on 30-Day Clinical Failure Rate in Patients With Uncomplicated Gram-Negative Bacteremia: A Randomized Clinical Trial. JAMA. 2020 Jun 2;323(21):2160-2169. doi: 10.1001/jama.2020.6348.

    PMID: 32484534DERIVED

  • 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.

    PMID: 28710229DERIVED

Study Officials

  • Angela Huttner, MD

    University of Geneva

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Masking Details
Participants, their care providers, and study investigators having contact with participants \& their providers will be blinded until the antibiotic therapy is discontinued. Outcomes assessors and data analysts will be fully blinded.
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: With day 1 defined as the first day of appropriate (microbiologically efficacious) antibacterial therapy, patients will be randomized 1:1:1 on day 5 (±1) to one of the following three arms: * "Fixed long" antibiotic course of 14 days (control arm) * "Fixed short" antibiotic course of 7 days (first intervention arm) * "Individualized" antibiotic course (second intervention arm): • Starting on day 5, therapy will be discontinued after the patient has been afebrile for 48 hours and the CRP level has decreased from its peak by at least 75% In all arms, the choice and mode of administration (IV vs. PO) of antibiotic(s) will be left to the patient's attending physician and consulting infectious disease specialist and thus will follow usual standards of care.
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Principal Investigator

Study Record Dates

First Submitted

March 29, 2017

First Posted

April 4, 2017

Study Start

April 27, 2017

Primary Completion

June 11, 2019

Study Completion

August 26, 2019

Last Updated

November 19, 2019

Record last verified: 2019-11

Data Sharing

IPD Sharing
Will not share

(There is no plan to share IPD.)

Locations

CH(3)