Gram-Negative Bloodstream Infection Oral Antibiotic Therapy Trial

Study Overview
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Brief Summary
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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
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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.

Official Title
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Gram-Negative Bloodstream Infection Oral Antibiotic Therapy Trial

Conditions
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Gram-negative Bacteremia

Intervention / Treatment
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* Drug: Intravenous Antibiotics
* Drug: Oral Antibiotics


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional 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.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Intravenous Antibiotics<br>IV antibiotics from the time of randomization to the completion of antibiotic treatment. Includes antibiotics such as ceftriaxone, cefepime, piperacillin-tazobactam, and meropenem. | Drug: Intravenous Antibiotics<br>* Participants will continue to receive intravenous antibiotics until the completion of the treatment course<br>|
| Active Comparator: Oral Antibiotics<br>Oral antibiotics from the time of randomization to the completion of antibiotic treatment, Includes antibiotics such as amoxicillin, cephalexin, ciprofloxacin, and trimethoprim-sulfamethoxazole. | Drug: Oral Antibiotics<br>* Participants will transition to oral antibiotics at the time of randomization and will continue oral antibiotics until the completion of the treatment course<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Desirability of Outcome Ranking (DOOR) | 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). | Day 30 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of All Cause Mortality | 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 | Day 30 | 
| Frequency of Recurrent infection | 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 | Day 30 | 
| Length of stay (days) | 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 | Day 30 | 
| Number of Participants with Treatment-related adverse events | 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 | Day 30 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gram-negative bacteremia, Antibiotic treatment, Antibiotic route, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Desirability of outcome ranking (DOOR)