Early Oral Step-down Antibiotic Therapy Versus Continuing Intravenous Therapy for Uncomplicated Gram-negative Bacteraemia (the INVEST Trial)

What this Trial Is About

Researchers are evaluating a new approach for managing uncomplicated Gram-negative bacteraemia, a bloodstream infection caused by certain bacteria. The study aims to compare the effects and costs of switching early to oral antibiotics within 72 hours after the first positive blood culture versus continuing standard intravenous (IV) antibiotic therapy. This international, open-label, phase IV trial involves clinically stable adult inpatients who are not critically ill and seeks to determine if the oral treatment is not worse than the IV treatment by a small margin. Participants are randomly assigned to one of two groups. In one group, patients switch to oral antibiotics such as fluoroquinolones (commonly ciprofloxacin) or trimethoprim-sulfamethoxazole within 72 hours after blood culture collection. Dosages are adjusted based on patient weight and kidney function. If oral treatment fails, patients can return to IV antibiotics. The other group continues IV antibiotics, such as ceftriaxone or cefazolin, for at least another 24 hours after randomization. The recommended total antibiotic course is about seven days but can be longer if needed. Patients may be discharged home or receive outpatient IV therapy as appropriate. During the study, researchers will monitor participants for outcomes like survival up to 90 days after randomization, days on IV antibiotics, adverse events, hospital stay length, readmissions, and quality of life scores. Data on health economics will also be collected. Follow-up assessments include evaluating mortality at 30 days, antibiotic use, treatment changes, and health-related quality of life at screening, end of treatment, and day 90. The study continues until July 2026, with careful monitoring of safety and treatment effects throughout.

Early Oral Switch for Uncomplicated Gram-negative Bacteraemia