Empirical Intravenous Beta-Lactam Plus Metronidazole Vs Oral Cefixime Plus Metronidazole for the Treatment of Liver Abscess

NCT06847126 | Recruiting Phase 3 DMC

• 1 other identifier: IEC-INT/2025/Study-2667
• Study Type: interventional
• Target: 220
• Locations: 1 country
• Sites: 1

Brief Summary

Liver abscess (LA) is potentially life threatening medical emergency requiring prompt medical intervention. The backbone of therapy is prompt empirical antimicrobial with or without percutaneous drainage/ aspiration of the abscess. The standard care for liver abscess includes empirical antimicrobials consisting both antibacterial and amoebicidal agents along with percutaneous drainage or aspiration of the collection. The antimicrobial regimen should cover against E. histolytica until microbial etiology is established or liver abscess of amoebic etiology is ruled out. But still there is no straightforward general agreement or evidence based on clinical studies regarding the standard protocol for empirical antimicrobials concerning choice, route of administration or duration of antimicrobials therapy. Most of the experts preferred intravenous antimicrobials over oral antimicrobials for the treatment of liver abscess with or without complication. But, there is no clinical trial evidence to support the rational of using intravenous antibiotics up front instead of oral antimicrobials. Recently published institutional study also suggested that empirical oral antimicrobials (Cefexime/Ciprofloxacin) were efficacious for the treatment of uncomplicated liver abscess, successfully managing around 90 % cases of liver abscess. When treating a liver abscess, the choice of antimicrobials and the administration technique must be specially tailored depending upon the existence of complications and the patient's clinical reaction. In the absence of clinical trials, the rational for using of intravenous broad spectrum antibiotics upfront instead of oral antimicrobials for the treatment of liver abscess with or without complications is doubtful and may appear injudicious contributing future rise of antimicrobial resistance. The use of intravenous antibiotics upfront may also unnecessarily lengthen hospital stays, enhance therapeutic expenditure, and raise the risk of hospital-acquired infections in patients who are capable for taking antimicrobials orally. Oral antimicrobials strategy will promote earlier discharge from the hospital and the patient can return to usual activities earlier. This study aims to provide valuable insights into the comparison and efficacy of empirical intravenous Beta-lactam antimicrobials plus Metronidazole and oral Cefixime plus Metronidazole therapy for the treatment of uncomplicated liver abscess. In this randomised controlled open label clinical trial all the patients with newly diagnosed liver abscess confirmed with radiology imaging, either by USG or CT scan, presenting at emergency or medical OPD will be screened for enrolment in the study. Following written informed consent from the participants and/or their legal guardian, those who meet the inclusion and exclusion criteria will be recruited in the study. Subsequently the participants will be randomized into either intravenous or oral antimicrobial group. The intravenous-group will receive Beta-lactam antimicrobials (i.e Piperacillin-Tazobactum 4.5g q 8 hourly or Ceftriaxone 1g q 12 hourly or Meropenem 1g q 8 hourly or Imipenem-Cilastatin 500mg q 6 hourly) Plus intravenous Metronidazole 750mg q 8 hourly for 2weeks. The oral-group will receive tablet Cefixime 200 mg q 12 hourly plus tablet Metronidazole 800 mg q 8 hourly for 2 weeks. Both the group will be provided standard care of therapy including percutaneous drainage or aspiration as per indication and will be followed up for 8 weeks. The primary outcome of clinical cure and secondary outcome of incidence of treatment failure, mortality, duration of antimicrobial therapy, recurrence, adverse drug reaction (ADR), complications will be compared between the groups.

Conditions

Liver Abscess

Keywords

Liver Abscess, Empirical antimicrobials, Beta-lactam antimicrobials, Intravenous, Oral, Cefixime, Metronidazole

Outcome Measures

Primary Outcomes (2)

• Clinical cure

  "clinical cure" is defined as defined as participants becoming asymptomatic with fever resolution for ≥48 hours, including USG demonstrating no drainable or aspiratable collection in the liver along with removal of the pigtail catheter if any.

  8 weeks

• Treatment failure

  "Treatment failure" is defined as the fulfilling of any one or more of the following conditions: 1. Persistently symptomatic even after 72 h of empirical antimicrobial therapy and percutaneous aspiration or drainage of the hepatic collection 2. Emergence of fresh or additional collection in the liver during the course of empirical antimicrobial therapy 3. Emergence of shock and or new onset organ failure (Encephalopathy, ARDS, AKI, MODS) during the course of therapy, leading to modification of oral antimicrobials to intravenous antimicrobials or up gradation of the ongoing intravenous antimicrobials 4. If pus culture demonstrates growth of microorganism which is not sensitive to the ongoing antimicrobials (intravenous Beta-lactam or oral Cefixime) along with inadequate clinical response to the therapy 5. Participants requiring persistent drainage or repeated aspiration of the abscess even after 4 weeks of empirical antimicrobial therapy

  8 weeks

Secondary Outcomes (6)

• Duration of the therapy

  8 weeks

• Need for prolong antibiotics therapy

  8 weeks

• Duration of hospital stay

  8 weeks

• Readmission

  8 weeks

• Recurrence of liver abscess

  8 weeks

Study Arms (2)

Intravenous Beta-Lactam antimicrobials

ACTIVE COMPARATOR

Intravenous beta-lactam antimicrobial for 2 weeks Plus Intravenous Metronidazole (750 mg q 8 hourly) for 2 weeks and standard care

Drug: Intravenous beta-lactam antimicrobial for 2 weeks Plus Intravenous Metronidazole (750 mg q 8 hourly) for 2 weeks; Other: Standard medical care

Oral Cefixime

ACTIVE COMPARATOR

Tablet Cefixime (200 mg q 12 hourly) for 2 weeks Plus Table Metronidazole (800 mg q 8 hourly) for 2 weeks and standard care

Drug: Tablet Cefixime (200 mg q 12 hourly) for 2 weeks Plus Tablet Metronidazole (800 mg q 8 hourly) for 2 weeks; Other: Standard medical care

Interventions

Intravenous beta-lactam antimicrobial for 2 weeks Plus Intravenous Metronidazole (750 mg q 8 hourly) for 2 weeks DRUG

Intravenous beta-lactam antimicrobial for 2 weeks Plus Intravenous Metronidazole (750 mg q 8 hourly) for 2 weeks and standard care

Also known as: Standard care

Intravenous Beta-Lactam antimicrobials

Tablet Cefixime (200 mg q 12 hourly) for 2 weeks Plus Tablet Metronidazole (800 mg q 8 hourly) for 2 weeks DRUG

Tablet Cefixime (200 mg q 12 hourly) for 2 weeks Plus Tablet Metronidazole (800 mg q 8 hourly) for 2 weeks

Also known as: Standard Medical care

Oral Cefixime

Standard medical care OTHER

Percutaneous drainage or aspiration of the abscess along resuscitative and symptomatic medications

Intravenous Beta-Lactam antimicrobials; Oral Cefixime

Eligibility Criteria

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

Sponsors & Collaborators

• Post Graduate Institute of Medical Education and Research, Chandigarh: lead

Study Sites (1)

Post Graduate Institute of Medical Education and Research (PGIMER)

Chandigarh, 160012, India

RECRUITING

MeSH Terms

Conditions

Liver Abscess

Interventions

WW Domain-Containing Oxidoreductase; Standard of Care

Condition Hierarchy (Ancestors)

Abdominal Abscess; Abscess; Suppuration; Infections; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Short Chain Dehydrogenase-Reductases; NAD (+) and NADP (+) Dependent Alcohol Oxidoreductases; Alcohol Oxidoreductases; Oxidoreductases; Enzymes; Enzymes and Coenzymes; Tumor Suppressor Proteins; Neoplasm Proteins; Proteins; Amino Acids, Peptides, and Proteins; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Central Study Contacts

Deba Prasad Dhibar, MD Medicine

CONTACT

+911722756670; drdeba_prasad@yahoo.co.in

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: February 21, 2025
• First Posted: February 26, 2025
• Study Start: February 25, 2025
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026
• Last Updated: April 13, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

IN (1)