Switch to Oral Antibiotics in Gram-negative Bacteremia

NCT04146922 | Completed DMC

• 1 other identifier: MRC-01-19-254
• Study Type: interventional
• Target: 176
• Locations: 4 countries
• Sites: 7

Brief 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.

Conditions

Escherichia Coli Bacteremia; Klebsiella Bacteraemia; Enterobacter Bacteraemia; Serratia Bacteraemia; Citrobacter Bacteraemia; Proteus Bacteraemia

Keywords

Enterobacteriaceae, bacteremia, step down oral therapy

Outcome Measures

Primary Outcomes (1)

• 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.

  90 days

Secondary Outcomes (5)

• Death from any cause.

  90 days

• Need for additional antimicrobial therapy with one or more microbiologically active agents before complete resolution of signs and symptoms of infection.

  Up to 90 days

• Microbiological relapse. 4)

  90 days

• Infection-related re-admission.

  90 days

• Hospital length of stay from date of first positive blood culture.

  Up to 90 days

Study Arms (2)

IV Group

ACTIVE COMPARATOR

Eligible patients randomized to complete their antimicrobial therapy course through intravenous (IV) administration.

Other: IV antimicrobial therapy

Oral Group

EXPERIMENTAL

Eligible patients randomized to step down to oral antimicrobial therapy for the remainder of their treatment course.

Other: Step down to oral antimicrobial therapy

Interventions

Step down to oral antimicrobial therapy OTHER

Step down from intravenous to oral antimicrobial therapy to complete the intended course of treatment.

Oral Group

IV antimicrobial therapy OTHER

No step down from intravenous to oral antimicrobial therapy to complete the intended course of treatment.

IV Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hamad Medical Corporation: lead

Study Sites (7)

Bahrain Defense Forces Hospital

Manama, Bahrain

Location

Farwaniya Hospital

Kuwait City, Kuwait

Location

Hamad Medical Corporation

Doha, Qatar

Location

Istanbul Medipol University

Istanbul, Turkey (Türkiye)

Location

Istanbul University Carrahpasa Medical School

Istanbul, Turkey (Türkiye)

Location

Marmara University School of Medicine

Istanbul, Turkey (Türkiye)

Location

Ordu University School of Medicine

Ordu, Turkey (Türkiye)

Location

Related Publications (1)

• Omrani AS, Abujarir SH, Ben Abid F, Shaar SH, Yilmaz M, Shaukat A, Alsamawi MS, Elgara MS, Alghazzawi MI, Shunnar KM, Zaqout A, Aldeeb YM, Alfouzan W, Almaslamani MA; SOAB Study Group. Switch to oral antibiotics in Gram-negative bacteraemia: a randomized, open-label, clinical trial. Clin Microbiol Infect. 2024 Apr;30(4):492-498. doi: 10.1016/j.cmi.2023.10.014. Epub 2023 Oct 18.

  PMID: 37858867 DERIVED

MeSH Terms

Conditions

Bacteremia

Condition Hierarchy (Ancestors)

Bacterial Infections; Bacterial Infections and Mycoses; Infections; Sepsis; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Ali S Omrani, FRCP FRCPath

  Hamad Medical Corporation

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Computer generated block randomization into permuted blocks of 4, 6 and 8

Study Record Dates

• First Submitted: October 20, 2019
• First Posted: October 31, 2019
• Study Start: October 13, 2019
• Primary Completion: August 30, 2022
• Study Completion: July 30, 2023
• Last Updated: August 14, 2023

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

KU (1); QA (1); TU (4); BA (1)