Gram-negative Bacteremia
Conditions
Keywords
Gram-negative bacteremia, Antibiotic treatment, Antibiotic route, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Desirability of outcome ranking (DOOR)
Brief summary
The Gram-negative bloodstream infection Oral Antibiotic Therapy trial (The GOAT Trial) is a multi-center, randomized clinical trial that hypothesizes that early transition to oral antibiotic therapy for the treatment of Gram-Negative BloodStream Infection (GN-BSI) is as effective but safer than remaining on intravenous (IV) antibiotic therapy for the duration of treatment.
Detailed description
This is an open-label, pragmatic, randomized trial of approximately 1,204 adult patients hospitalized across 9 United States hospitals with the overarching goal of determining whether the optimal approach for the management of GN-BSI is (1) IV antibiotics for the duration of treatment or (2) initial IV antibiotics followed by early transition to oral antibiotics for the duration of treatment. Patients will be randomized in a 1:1 ratio to remain on IV antibiotics or transition to oral antibiotics as soon as possible after blood culture collection, but no more than 5 days later. The primary objective is to compare the Desirability of Outcomes Ranking (DOOR) distributions between patients with GN-BSI receiving IV antibiotic treatment only versus patients transitioned early to oral antibiotic treatment. The study hypothesis is that oral treatment will result in a more favorable DOOR distribution than IV treatment, likely as a result of differential adverse events and changes in Quality of Life (QoL) profiles.
Interventions
Participants will continue to receive intravenous antibiotics until the completion of the treatment course
DRUGOral Antibiotics
Participants will transition to oral antibiotics at the time of randomization and will continue oral antibiotics until the completion of the treatment course
Sponsors
Johns Hopkins University
Patient-Centered Outcomes Research Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Eligible participants with GN-BSI will be randomized to (arm 1) IV antibiotics or (arm 2) oral antibiotics for the treatment of GN-BSI.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult (≥ 18 years) at the time of screening * Hospitalized * Identification of at least one Gram-negative organism in a blood culture * Capable of providing written informed consent (includes through a legally authorized representative) * Willingness to adhere to assigned study arm * Capable and willing to complete a follow-up QoL interview (including through a legally authorized representative)
Exclusion criteria
* Unable to tolerate or absorb a course of oral antibiotics * Actively receiving vasopressors * Gram-negative organism not susceptible to any oral antibiotics * Gram-negative organism not susceptible to any IV antibiotics * Polymicrobial bloodstream infection * The following patients with polymicrobial infections remain eligible for enrollment: (1) more than one morphology or species of a gram-negative organism (except for Acinetobacter baumannii or Stenotrophomonas maltophilia), (2) a single positive blood culture with a common commensal organism (grown in addition to an Enterobacterales species or Pseudomonas aeruginosa * Allergy or contraindication rendering no oral option or no IV option for therapy with the listed antibiotic agents. * Anticipated duration of therapy greater than 14 days * Central nervous system infection * Absolute neutrophil count of \<500 cells/mL or anticipated to reduce to \<500 cells/mL during the antibiotic treatment course. * Receiving hospice care
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Desirability of Outcome Ranking (DOOR) | Day 30 | Each participant will be placed in 1 of 5 DOOR levels based on overall clinical response and treatment-related adverse events (AE). The 5 DOOR levels are as follows: successful clinical response and no treatment-related AE (Level 1); mild suboptimal clinical response or mild treatment-related AE (Level 2); moderate suboptimal clinical response or moderate treatment-related AE (Level 3); significant suboptimal clinical response or significant treatment-related AE (Level 4); death (Level 5). The distribution of participants in the five DOOR levels will be used to ultimately determine which treatment approach is superior for the management of GN-BSI (i.e., IV antibiotic treatment or early transition to oral antibiotic treatment). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of All Cause Mortality | Day 30 | 30-day all cause mortality will be compared between adults with GN-BSI receiving IV antibiotic treatment only versus those transitioned early to oral antibiotic treatment |
| Frequency of Recurrent infection | Day 30 | 30-day recurrent infection with the same bacterial species will be compared between adults with GN-BSI receiving IV antibiotic treatment only versus those transitioned early to oral antibiotic treatment |
| Length of stay (days) | Day 30 | Hospital length of stay will be compared between adults with GN-BSI alive at day 30 receiving IV antibiotic treatment only versus those transitioned early to oral antibiotic treatment |
| Number of Participants with Treatment-related adverse events | Day 30 | Moderate to severe treatment-related AEs will be compared between adults with GN-BSI receiving IV antibiotic treatment only versus those transitioned early to oral antibiotic treatment |
Countries
United States
Contacts
CONTACTPranita D Tamma, MD, MHS
CONTACTSara E Cosgrove, MD, MS
PRINCIPAL_INVESTIGATORPranita D Tamma, MD, MHS
Children's Hospital of Philadelphia
PRINCIPAL_INVESTIGATORSara E Cosgrove, MD, MS
Johns Hopkins University
Outcome results
None listed