Switch to Oral Antibiotics in Gram-negative Bacteremia (SOAB)

  • STATUS
    Recruiting
  • End date
    Sep 30, 2023
  • participants needed
    438
  • sponsor
    Hamad Medical Corporation
Updated on 18 April 2022

Summary

Eligible subjects will be those age 18 years or more with mono-microbial blood stream infection caused by E. coli, Klebsiella species, Enterobacter species, Serratia species, Citrobacter species, or Proteus species, who have achieved adequate source control, are afebrile and hemodynamically stable for 48 hours or more and have received microbiologically active intravenous therapy for 3-5 days. The bloodstream isolate must be susceptible to amoxicillin, amoxicillin-clavulanate, fluoroquinolones, oral cephalosporins and/or trimethoprim-sulfamethoxazole and the subject must be able to take oral medication directly or through a feeding tube. Exclusions criteria include allergy to all in-vitro active antimicrobials which are available in oral formulations, pregnancy, infective endocarditis, central nervous system infection, terminal illness with expected survival less than 14 days, absolute neutrophil count less than 1,000/ml and hematopoietic or solid organ transplantation within the preceding 90 days. Randomization will be stratified by urinary versus non-urinary source of bacteremia. The primary outcome is treatment failure at 90-days with 10% margin for non-inferiority in the 95% confidence interval around the difference in outcome between the two study groups.

Description

Oral antimicrobial therapy mitigates vascular line associated complications such as infection, thrombosis and pain, facilitating early mobilization and discharge and reducing healthcare costs. Efficacy and safety of step-down to oral antimicrobial therapy in patients with Enterobacteriaceae bacteremia has never been confirmed in a randomized clinical trial. The aim of this clinical trial is to evaluate the safety and efficacy of oral step down strategy in patients with Gram-negative blood stream infections.

Eligible subjects will be those age 18 years or more with mono-microbial blood stream infection caused by E. coli, Klebsiella species, Enterobacter species, Serratia species, Citrobacter species, or Proteus species, who have achieved adequate source control, are afebrile and hemodynamically stable for 48 hours or more and have received microbiologically active intravenous therapy for 3-5 days. The bloodstream isolate must be susceptible to amoxicillin, amoxicillin-clavulanate, fluoroquinolones, oral cephalosporins and/or trimethoprim-sulfamethoxazole and the subject must be able to take oral medication directly or through a feeding tube. Exclusions criteria include allergy to all in-vitro active antimicrobials which are available in oral formulations, pregnancy, infective endocarditis, central nervous system infection, terminal illness with expected survival less than 14 days, absolute neutrophil count less than 1.0x109/L and hematopoietic or solid organ transplantation within the preceding 90 days.

The primary endpoint is treatment failure at 90-days, defined as a composite of the death from any cause, need for additional antimicrobial therapy with one or more microbiologically active agents before complete resolution of signs and symptoms of infection, microbiological relapse (same species from any clinical site) and infection-related re-admission.

Eligible subjects will be randomized using permuted blocks of variable sizes to full intravenous antimicrobial therapy course (IV Group) or intravenous followed by step-down to oral therapy (PO Group). Randomization will be stratified by urinary versus non-urinary source of bacteremia. The primary analysis will include all patients who were randomized and received at least one dose of the assigned treatment. The difference in primary outcome rate between the intervention and control groups will be presented alongside a 95% confidence interval (CI), calculated using the method of Mietennen and Nurminen. If the upper limit of the 95% CI for the difference in overall response is below 10%, non-inferiority will be concluded.

A Data and Safety Monitoring Board (DSMB) will oversee the trial. An interim analysis will be performed after the first 50% of the target sample have completed the 90-day study period. DMSB can make a binding recommendation to terminate the study if the results of the interim analysis indicate very high likelihood for positive effect or futility.

Details
Condition Escherichia Coli Bacteremia, Klebsiella Bacteraemia, Enterobacter Bacteraemia, Serratia Bacteraemia, Citrobacter Bacteraemia, Proteus Bacteraemia
Treatment Step down to oral antimicrobial therapy, IV antimicrobial therapy
Clinical Study IdentifierNCT04146922
SponsorHamad Medical Corporation
Last Modified on18 April 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Age ≥18 years
Mono-microbial blood stream infection
Isolation of E. coli, Klebsiella species, Enterobacter species, Serratia species, Citrobacter species, or Proteus species from ≥1 blood culture(s)
Adequate source control within ≤5 days of staring in-vitro active intravenous antimicrobial therapy
Afebrile (Tmax <38 degrees Celsius) for ≥48 hours
Hemodynamically stable for ≥48 hours (SBP ≥100 mmHg, no vasopressors)
Microbiologically active intravenous therapy for 3-5 days
Bloodstreams isolate in-vitro susceptibility to amoxicillin, amoxicillin-clavulanate, fluoroquinolones, oral cephalosporins and/or trimethoprim-sulfamethoxazole
Ability to take oral medication directly or through a feeding tube

Exclusion Criteria

Allergy to all in-vitro active antibiotics which are available in oral formulations
Pregnancy
Infective endocarditis
Central nervous system infection
Terminal illness with expected survival <14 days
Neutropenia (absolute neutrophil count <1.0x10^9/L)
Hematopoietic or solid organ transplantation within the preceding 90 days
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact

site

0/250

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note