An interventional study of Step down to oral antimicrobial therapy and IV antimicrobial therapy in Escherichia Coli Bacteremia, Klebsiella Bacteraemia and Enterobacter Bacteraemia, sponsored by Hamad Medical Corporation. Completed at 7 sites in 4 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-08-14.
Sponsored by Hamad Medical Corporation · Not applicable, Interventional, and Treatment
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.
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.
297 studies on the registry are indexed under Bacteremia; 51 are open to participants now.
This study's enrollment of 176 is above the median of 156 across 156 interventional studies indexed under Bacteremia.
Browse Bacteremia studies →Hamad Medical Corporation is the lead sponsor of 139 studies on the registry; 27 are open to participants now.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Absolute neutrophil count (ANC)
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Eligible patients randomized to complete their antimicrobial therapy course through intravenous (IV) administration.
Other: IV antimicrobial therapy
Eligible patients randomized to step down to oral antimicrobial therapy for the remainder of their treatment course.
Other: Step down to oral antimicrobial therapy
Step down from intravenous to oral antimicrobial therapy to complete the intended course of treatment.
No step down from intravenous to oral antimicrobial therapy to complete the intended course of treatment.
Treatment failure.
Defined as death, need for additional active antibiotic therapy before resolution of all signs and symptoms of infection, microbiological relapse or infection-related re-admission within 90 days of commencement of active intravenous antimicrobial therapy.
Time frame: 90 days
Death from any cause.
Death from any cause during follow up period.
Time frame: 90 days
Need for additional antimicrobial therapy with one or more microbiologically active agents before complete resolution of signs and symptoms of infection.
Need for additional active antimicrobial therapy before resolution of signs and symptoms of infection; defined as recovery from infection-related symptoms present at baseline (e.g.; urinary symptoms, abdominal pain, jaundice ..etc), no recurrence of fever (Tmax ≥38.0oC).
Time frame: Up to 90 days
Microbiological relapse. 4)
Active infection in any site caused by the same species in the index blood culture.
Time frame: 90 days
Infection-related re-admission.
Re-admission to hospital because of any active infection.
Time frame: 90 days
Hospital length of stay from date of first positive blood culture.
Hospital length of stay from date of first positive blood culture.
Time frame: Up to 90 days
Plan to share: No
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Ran from Oct 2019 to primary completion in Aug 2022, 34 months.
Of 35 interventional studies with no phase under Bacteremia, half reached primary completion within 34 months of starting (the median), counting those still running; a quarter within 13 and three quarters within 64. This study's 34 months is close to that.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Mar 2022. You cannot join it, but the record below documents what was studied.
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