GOAT: Gram-Negative Bloodstream Infection Oral Antibiotic Therapy Trial

• Sponsor: Johns Hopkins University (Other)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT06080698
• Collaborator: Patient-Centered Outcomes Research Institute (Other)
• Enrollment: 1,204
• Arms: 2
• Anticipated Duration (Months): 41.9

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Gram-negative Bacteremia	Drug: Intravenous Antibiotics; Drug: Oral Antibiotics	N/A

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 Design

• Study Type: Interventional
• Anticipated Enrollment: 1204 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• 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.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)
• Primary Purpose: Treatment
• Official Title: Gram-Negative Bloodstream Infection Oral Antibiotic Therapy Trial
• Anticipated Study Start Date: Jan 1, 2024
• Anticipated Primary Completion Date: May 31, 2027
• Anticipated Study Completion Date: Jun 30, 2027

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 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.	Drug: Intravenous Antibiotics; Participants will continue to receive intravenous antibiotics until the completion of the treatment course
Active Comparator: 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.	Drug: Oral Antibiotics; Participants will transition to oral antibiotics at the time of randomization and will continue oral antibiotics until the completion of the treatment course

Outcome Measures

Primary Outcome Measures

1. 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

1. 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

2. 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

3. 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

4. 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Johns Hopkins University
• Patient-Centered Outcomes Research Institute

Investigators

• Principal Investigator: Pranita D Tamma, MD, MHS, Johns Hopkins University
• Principal Investigator: Sara E Cosgrove, MD, MS, Johns Hopkins University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Johns Hopkins University
• ClinicalTrials.gov Identifier: NCT06080698
• Other Study ID Numbers: IRB00390397; CER-2022C1-26099
• First Posted: Oct 12, 2023
• Last Update Posted: Oct 12, 2023
• Last Verified: Oct 1, 2023

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Keywords provided by Johns Hopkins University: Gram-negative bacteremia; Antibiotic treatment; Antibiotic route; Escherichia coli; Pseudomonas aeruginosa; Klebsiella pneumoniae; Desirability of outcome ranking (DOOR)
• Additional relevant MeSH terms: Bacteremia; Sepsis; Anti-Bacterial Agents; Antibiotics, Antitubercular

Study Results

No Results Posted as of Oct 12, 2023