Non-Inferiority Trial on 3-Week vs. 6-Week Antibiotic Regimen in Drained Pyogenic Liver Abscess Using Meropenem, Linezolid, and Tedizolid

The primary objective is to demonstrate the non-inferiority of a 3-week antibiotic therapy duration compared to a 6-week duration regarding treatment failure at 12 weeks following the drainage of a pyogenic liver abscess. The secondary objectives include:

• Demonstrating non-inferiority in terms of all-cause mortality.
• Evaluating the superiority of the 3-week regimen regarding the emergence of digestive colonization by multidrug-resistant bacteria.
• Comparing the proportion of patients experiencing treatment failure at the end of the assigned antibiotic course.
• Comparing the proportion of complete radiological regression of the abscess at 3, 6, and 12 weeks post-drainage.
• Comparing the duration of hospital discharge.
• Describing intercurrent events, such as relapse or new abscess formation, between 12 weeks and 6 months.
• Characterizing the clinical, anatomical, and microbiological features of the abscesses.
• Describing the characteristics and modalities of the administered antibiotics.
• Identifying risk factors for treatment failure.
• Evaluating the safety of each treatment protocol.

The sponsor did not provide information regarding the total number of participants. The study population consists of male and female patients diagnosed with pyogenic liver abscess. Participants are within the age ranges corresponding to codes 3 and 4. Inclusion requires an intra-hepatic abscess confirmed by computed tomography and bacterial confirmation through culture of pus extracted from the abscess. Successful drainage, via percutaneous drainage or aspiration, must be demonstrated by a reduction in abscess size greater than 50% on ultrasonography or computed tomography at 10 days following the procedure.

This non-inferiority trial is designed to compare the optimal duration of antibiotic therapy in patients with a drained pyogenic liver abscess. The research methodology involves a comparison between a 3-week treatment regimen and a 6-week treatment regimen. The primary objective is to demonstrate that 3 weeks of therapy is non-inferior to 6 weeks in terms of treatment failure evaluated at week 12 following drainage. Participants must be at least 18 years of age and present with an intra-hepatic abscess confirmed by radiological evaluation and bacterial confirmation via pus culture. Successful drainage, defined by a specific reduction in abscess size on ultrasonography or computed tomography, is also required for inclusion. The study protocol includes an initial screening process, followed by the assigned treatment period and subsequent follow-up visits to assess clinical, anatomical, and microbiological outcomes through week 12 and potentially up to month 6. The estimated recruitment period for the study spans from September 2025 to March 2029.

The clinical trial evaluates the non-inferiority of different durations of antibiotic therapy for the treatment of pyogenic liver abscess. The experimental treatments include various pharmacological agents administered for either 3 weeks or 6 weeks.

Meropenem combined with vaborbactam is administered via intravenous use.

Linezolid is administered via oral use.

Tedizolid is administered via oral use.

Sulfamethoxazole and trimethoprim, including bromhexine hydrochloride, are administered via oral use.

Ceftazidime and a beta-lactamase inhibitor, specifically avibactam, are administered via intravenous use.

Penicillins are administered via oral use.

Daptomycin is administered via intravenous use.

Other antibacterials are administered via intravenous use.

Colistin is administered via intravenous use.

Fluoroquinolones are administered via oral use.

Metronidazole, containing glucose, is administered via oral use.

Amikacin, in the form of amikacin sulfate, is administered via intravenous use.

Imipenem, combined with cilastatin and relebactam, is administered via intravenous use.

The primary efficacy endpoint is the proportion of patients experiencing treatment failure between the end of the antibiotic therapy and week 12 following the drainage of the pyogenic liver abscess. Secondary endpoints include the time to death from any cause and the time to hospital discharge. The assessment of digestive colonization of multidrug-resistant bacteria is conducted at inclusion and at week 12 after drainage using rectal swabs. The proportion of participants with complete regression of liver abscess imaging is evaluated at week 3, week 6, and week 12 after drainage. Additional secondary measures involve the incidence of adverse events and serious adverse events, the proportion of participants with treatment failure at the end of the assigned antibiotic therapy, and the proportion of patients receiving extended antibiotic therapy beyond the randomized duration. Furthermore, the proportion of patients receiving appropriate antibiotic therapy based on bacterial documentation will be monitored. The study also tracks intercurring events, such as relapse of the index infection, new liver abscesses, or death, occurring between week 12 and month 6.