Ciprofloxacin Plus Metronidazole Vs Cefixime Plus Metronidazole Therapy for the Treatment of Liver Abscess

NCT03969758 | Unknown Phase 3

• 1 other identifier: INT/IEC/2019/001028
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 1

Brief Summary

Liver abscess is purulent collections in the liver parenchyma that result from microbial infection spread to the liver through the biliary tree, hepatic or portal vein and by extension of adjacent infection or as a result of trauma. Liver abscesses are most commonly pyogenic followed by amoebic and rarely tuberculous or fungal in immunocompromised patients. In the developing country amoebic liver abscess is more frequent than the developed country but secondary bacterial infection of amoebic liver abscess and polymicrobial pyogenic liver abscess are also common. Pyogenic liver abscess is commonly a polymicrobial infection caused by mixed enteric facultative and anaerobic pathogens. The most commonly isolated organisms are Escherichia coli, Klebsiella pneumoniae, Streptococcus constellatus, Streptococcus anginosus, Streptococcus intermedius, Enterococcus and anaerobes, including Bacteroidesfragilis and Fusobacteriumnecrophorum. Amoebic liver abscess most frequently occur following infection with the parasite Entamoeba histolytica. Liver abscess is a common medical emergency. Prompt empirical antimicrobial with or without percutaneous aspiration or drainage of the abscess is therapeutic. An empiric antimicrobial regimen for liver abscess should cover enteric gram-negative bacilli, streptococci, anaerobes and antamoebahistolytica. Presently a Fluoroquinolone (Ciprofloxacin, Levofloxacin) or a Third or Fourth generation Cefalosporine (Cefixime, Ceftriaxone, cefepime) or a Beta-lactam-beta-lactamase inhibitor combination (piperacillin-tazobactam or ticarcillin-clavulanate) or a Carbapenem (Imipenem-cilastatin, Meropenem, Doripenem, Ertapenem) are being used in combination with or without Metronidazole as the empirical antimicrobial regime for the treatment live abscess. There is no randomized controlled clinical trial to evaluated and compare efficacy of the antimicrobial regimens for the treatment of liver abscess as well as there is no specific treatment guideline for the use of empirical antibiotics. There is also no definite proven rational for using Cefalosporine, Beta-lactam-beta-lactamase inhibitor combination or Carbapenem upfront, not using Fluoroquinolone in empirical antibiotic regimen for the treatment of liver abscess. Injudicious use of broader spectrum antibiotics may also lead to rise in antibiotic resistance in future. Both ciprofloxacin and Cefixime are effective oral antibiotics as they are well-absorbed orally with good oral bioavailability and achieve plasma concentration well above the minimal inhibitory concentrations require for the killing of the microorganism. Using intravenous (IV) antibiotics upfront, for the treatment of liver abscess in patients who can take orally may unnecessary increase the duration of hospital stay, healthcare burden and the cost of therapy, as well as the risk of hospital acquired infection. So the investigators have planned this randomized controlled double blind study to evaluate the efficacy of empirical Ciprofloxacin plus Metronidazole and Cefixime plus Metronidazole therapy for the treatment of liver abscess and to compare the outcomes of two different empirical antibiotics regimen.

Conditions

Liver Abscess

Outcome Measures

Primary Outcomes (1)

• Clinical cure

  Asymptomatic and afebrile for more than 48 hours, along with USG showing no drainable collection in the liver with removal of the pigtail catheter if any

  2 weeks

Secondary Outcomes (9)

• Treatment failure

  8 weeks

• All-cause mortality

  8 weeks

• Recurrence of liver abscess

  8 weeks

• Need for surgical intervention

  8 weeks

• Need for mechanical ventilation

  8 weeks

Study Arms (2)

Ciprofloxacin plus Metronidazole therapy

ACTIVE COMPARATOR

Will receive tablet Ciprofloxacin (500 mg BDS) and tablet Metronidazole (800 mg TDS) orally for 2 weeks. Percutaneous aspiration or drainage of the liver abscess will be done for all the participants when there is enough liquid content/pus which is amenable for aspiration or drainage. Percutaneous drainage or aspiration will be done in liver abscess with size of ≥ 5 cm and \<5 cm respectively. After 2 weeks of empirical antibiotic therapy, asymptomatic patients with persistent drainage with USG showing significant drainable collection in the liver will receive another 2 weeks of extended antimicrobial therapy of same combination.

Drug: Ciprofloxacin

Cefixime plus Metronidazole Therapy

ACTIVE COMPARATOR

Will receive tablet Cefixime (200 mg BDS) and tablet Metronidazole (800 mg TDS) orally for 2 weeks.Percutaneous aspiration or drainage of the liver abscess will be done for all the participants when there is enough liquid content/pus which is amenable for aspiration or drainage. Percutaneous drainage or aspiration will be done in liver abscess with size of ≥ 5 cm and \<5 cm respectively. After 2 weeks of empirical antibiotic therapy, asymptomatic patients with persistent drainage with USG showing significant drainable collection in the liver will receive another 2 weeks of extended antimicrobial therapy of same combination.

Drug: Cefixime

Interventions

Ciprofloxacin DRUG

will receive tablet Ciprofloxacin (500 mg BDS) and tablet Metronidazole (800 mg TDS) for 2 weeks orally. Percutaneous aspiration or drainage of the liver abscess will be done when there is enough liquid content/pus amenable for aspiration or drainage. Percutaneous drainage or aspiration will be done in liver abscess with size of ≥ 5 cm and \<5 cm respectively.

Also known as: Metronidazole, Percutaneous drainage or aspiration of the liver abscess

Ciprofloxacin plus Metronidazole therapy

Cefixime DRUG

will receive tablet Cefixime (200 mg BDS) and tablet Metronidazole (800 mg TDS) for 2 weeks orally. Percutaneous aspiration or drainage of the liver abscess will be done when there is enough liquid content/pus amenable for aspiration or drainage. Percutaneous drainage or aspiration will be done in liver abscess with size of ≥ 5 cm and \<5 cm respectively.

Also known as: Metronidazole, Percutaneous drainage or aspiration of the liver abscess

Cefixime plus Metronidazole Therapy

Eligibility Criteria

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

You may qualify if:

• Irrespective of gender
• Age ≥ 18 years
• Symptomatic patients of liver abscess confirmed with radiology imaging, either by ultrasonography (USG) or computed tomographgy (CT) scan

You may not qualify if:

• Past history of liver abscess
• Chronic kidney disease (CKD)
• History of hypersensitivity to either Ciprofloxacin or Metronidazole or Cefixime
• Shock (blood pressure \<90/60 mmHg) at presentation
• ARDS (PaO2/FiO2≤300)
• Encephalopathy (altered sensorium with GCS \<15)
• Acute kidney injury (AKI, Increase in serum creatinine to ≥1.5 times from the baseline)
• Pregnancy at presentation
• Already received antibiotics for more than 48 hours prior to the admission
• Not able to take orally
• Receiving blood thinners like anti-platelets, anti-coagulation agents within 4 weeks of presentation

Sponsors & Collaborators

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

Study Sites (1)

Post Graduate Institute of Medical Education and Research

Chandigarh, 160012, India

Location

Related Publications (1)

• Priya G L, Dhibar DP, Saroch A, Sharma N, Sharma V, Verma N, Chaluvashetty SB, Prakash A, Kaur H. Efficacy of empirical Ciprofloxacin or Cefixime plus Metronidazole therapy for the treatment of liver abscess: a randomized control clinical trial. Sci Rep. 2024 May 20;14(1):11430. doi: 10.1038/s41598-024-59607-1.

  PMID: 38769330 DERIVED

MeSH Terms

Conditions

Liver Abscess

Interventions

Ciprofloxacin; Metronidazole; Cefixime

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nitroimidazoles; Nitro Compounds; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Cefotaxime; Cephacetrile; Cephalosporins; beta-Lactams; Lactams; Amides; Thiazines; Sulfur Compounds

Study Officials

• Deba P Dhibar, MD

  PGIMER, Chandigarh, India

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Deba P Dhibar, MD

CONTACT

+91722756670; drdeba_prasad@yahoo.co.in

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Double Blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: May 22, 2019
• First Posted: May 31, 2019
• Study Start: July 1, 2019
• Primary Completion: May 1, 2020
• Study Completion: May 1, 2020
• Last Updated: July 22, 2019

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will not share

Locations

IN (1)