Gram-Negative Bloodstream Infection Oral Antibiotic Therapy Trial

Gram-negative Bacteremia Clinical Trial

— GOAT  

Official title:

Gram-Negative Bloodstream Infection Oral Antibiotic Therapy Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06080698
• Other study ID #: IRB00390397
• Secondary ID: CER-2022C1-26099
• Status: Recruiting
• Phase: N/A
• Start date: February 22, 2024
• Est. completion date: June 30, 2027

Study information

• Verified date: March 2024
• Source: Johns Hopkins University
• Contact: Pranita D Tamma, MD, MHS
• Phone: 410-614-1492
• Email: ptamma1[@]jhmi.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1204
• Est. completion date: June 30, 2027
• Est. primary completion date: May 31, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Bacteremia
• Gram-negative Bacteremia
• Sepsis

Intervention

Drug:
• Intravenous Antibiotics
Participants will continue to receive intravenous antibiotics until the completion of the treatment course
• 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

Locations

Country	Name	City	State
United States	University of Maryland Medical Center	Baltimore	Maryland
United States	Denver Health Hospital Authority	Denver	Colorado
United States	Duke University	Durham	North Carolina
United States	Houston Methodist	Houston	Texas
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Rutgers-RWJ University Hospital	New Brunswick	New Jersey
United States	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	Mayo Clinic	Rochester	Minnesota
United States	University of California, San Francisco	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
Johns Hopkins University	Patient-Centered Outcomes Research Institute

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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