Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04146922 |
| Other study ID # |
MRC-01-19-254 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
October 13, 2019 |
| Est. completion date |
July 30, 2023 |
Study information
| Verified date |
March 2022 |
| Source |
Hamad Medical Corporation |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial 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), adjusted by source of bacteremia. 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 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.
The Data and Safety Monitoring Board 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.
