Gram-Negative Bloodstream Infection Oral Antibiotic Therapy Trial

Not Applicable

Recruiting

• Conditions: Gram-negative Bacteremia
• Interventions: Drug: Intravenous Antibiotics; Drug: Oral Antibiotics

• Registration Number: NCT06080698
• Lead Sponsor: Johns Hopkins University

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.

Study Timeline

• Study First Submitted: 2023-10-02
• Study First Submitted QC: 2023-10-06
• Study First Posted: 2023-10-12
• Study Start: 2024-02-22
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-19
• Last Update Posted: 2025-03-24
• Primary Completion: 2027-05-31
• Study Completion: 2027-06-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 1204

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Intravenous Antibiotics	Intravenous Antibiotics	IV antibiotics from the time of randomization to the completion of antibiotic treatment. Includes antibiotics such as ceftriaxone, cefepime, piperacillin-tazobactam, and meropenem.
Oral Antibiotics	Oral Antibiotics	Oral antibiotics from the time of randomization to the completion of antibiotic treatment, Includes antibiotics such as amoxicillin, cephalexin, ciprofloxacin, and trimethoprim-sulfamethoxazole.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (11)

Johns Hopkins University Hospital Systems; 🇺🇸 Baltimore, Maryland, United States

Carilion Clinic; 🇺🇸 Roanoke, Virginia, United States

University of California, San Francisco; 🇺🇸 San Francisco, California, United States

Denver Health Hospital Authority; 🇺🇸 Denver, Colorado, United States

University of Maryland Medical Center; 🇺🇸 Baltimore, Maryland, United States

Mayo Clinic; 🇺🇸 Rochester, Minnesota, United States

Rutgers-RWJ University Hospital; 🇺🇸 New Brunswick, New Jersey, United States

Duke University; 🇺🇸 Durham, North Carolina, United States

Hospital of the University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States

Vanderbilt University Medical Center; 🇺🇸 Nashville, Tennessee, United States

Houston Methodist; 🇺🇸 Houston, Texas, United States